1,3-Allylic Strain (A¹,³)
Definition: Steric/electronic repulsion across allylic systems affecting conformation and selectivity.
Context: Explains axial selectivity and diastereocontrol.
Example: Asymmetric allylation reactions.
Related Terms: A-Values, Stereoelectronic Effects.
Reference: Hoffmann, Acc. Chem. Res. (1971).
1,3-Diaxial Interaction
Definition: Steric interactions between axial substituents on cyclohexane separated by one carbon.
Context: Dictates conformational preferences relevant to reactivity.
Example: Axial methyl interactions.
Related Terms: A-Values, Conformation.
Reference: Eliel & Wilen (1994).
A-Values
Definition: Quantitative measure of axial vs equatorial preference in cyclohexanes.
Context: Predicts conformational populations and stereochemical outcomes.
Example: t-Bu substituent has large A-value.
Related Terms: Conformation, 1,3-Diaxial Interactions.
Reference: Eliel & Wilen (1994).
Absolute Asymmetric Synthesis
Definition: Formation of an enantiomeric excess without any chiral influence (no chiral reagents or fields).
Context: Mechanistic interest and potential origin-of-chirality implications.
Example: Soai asymmetric autocatalysis.
Related Terms: Asymmetric Amplification, Soai Reaction.
Reference: Soai, Nature (1995).
Absolute Configuration
Definition: The unambiguous description of the spatial arrangement of substituents (e.g., R/S).
Context: Required in regulatory submissions and labeling of chiral APIs.
Example: R- and S-thalidomide.
Related Terms: R/S Configuration, CIP Rules.
Reference: IUPAC Gold Book.
Achiral
Definition: A molecule or object that is superimposable on its mirror image.
Context: Achirality implies the absence of optical activity and stereochemical differentiation. Such molecules do not exhibit enantiomeric forms.
Example: Methane, Dichloromethane (lack stereogenic center), Meso-tartaric acid is achiral despite having two stereocenters.
Related Terms: Chiral; Symmetry; Plane of symmetry; Meso-compound.
Reference: IUPAC. Compendium of Chemical Terminology (IUPAC Gold Book), 2nd Edition, 1997 (updated 2019).
Allenes
Definition: Cumulenes (C=C=C) that can be chiral due to orthogonal π systems.
Context: Provide axial chirality in drug scaffolds and ligands.
Example: Chiral 1,3-disubstituted allenes.
Related Terms: Axial Chirality, Atropisomerism.
Reference: Eliel & Wilen (1994).
Analytical Method Validation (Chiral)
Definition: Validation of chiral analytical procedures for specificity, accuracy, precision, and robustness.
Context: Required for release and stability testing of chiral APIs.
Example: Validation of chiral HPLC method for enantiomeric purity.
Related Terms: ICH Q2(R2), Chiral HPLC.
Reference: ICH Q2(R2) (2022).
Anisotropy Factor (g)
Definition: CD intensity normalized to absorbance (Δε/ε).
Context: Enables quantitative comparison of chiroptical responses; important in CPL materials.
Example: g ~ 10-3; for many organic chromophores.
Related Terms: CD, CPL.
Reference: Barron (2004).
Anomer
Definition: A subtype of epimer differing at the anomeric carbon in cyclic sugars.
Context: Critical in carbohydrate chemistry, anomeric configuration influences stability, solubility, and biological recognition.
Example: α-D-glucose vs β-D-glucose.
Related Terms: Epimer, Anomeric Effect, Carbohydrate Stereochemistry.
Reference: IUPAC Gold Book.
Anomeric Effect
Definition: Preference for axial orientation of electronegative substituents at the anomeric center in pyranoses.
Context: Influences glycoside stability and reactivity in medicinal chemistry.
Example: Axial methoxy in methoxytetrahydropyran.
Related Terms: Stereoelectronic Effect, Carbohydrate Stereochemistry.
Reference: Deslongchamps (1983).
Anti-(Stereochemical Descriptor)
Definition: Describes two substituents or groups positioned on opposite sides of a reference plane or dihedral angle (180° apart).
Context: Used to describe relative configuration in alkenes, aldols, and conformational analysis.
Example: Anti-periplanar geometry in E2 eliminations or anti-diol configurations.
Related Terms: Syn; Antiperiplanar; Synclinal.
Reference: IUPAC. Compendium of Chemical Terminology (IUPAC Gold Book), 2nd Edition, 1997 (updated 2019).
Asymmetric Amplification
Definition: Small initial enantiomeric bias is amplified during reaction or crystallization.
Context: Useful in chiral self-replication and deracemization protocols.
Example: Soai reaction ee amplification.
Related Terms: Absolute Asymmetric Synthesis.
Reference: Soai, Nature (1995); Blackmond, PNAS (2004).
Asymmetric Catalysis
Definition: Catalysis that yields one enantiomer preferentially.
Context: Cornerstone of modern manufacturing of single-enantiomer drugs.
Example: Noyori asymmetric hydrogenation.
Related Terms: Organocatalysis, Biocatalysis.
Reference: Noyori, Nobel Lecture (2001).
Asymmetric Transfer Hydrogenation (ATH)
Definition: Hydrogen transfer from donors (iPrOH, formate) to substrates using chiral catalysts.
Context: Avoids H? gas; scalable and selective.
Example: Noyori–Ikariya systems reducing ketones.
Related Terms: Noyori Hydrogenation, Organocatalysis.
Reference: Ikariya & Noyori, Acc. Chem. Res. (2007).
Atropisomerism
Definition: Stereoisomerism due to hindered rotation that creates isolable enantiomers.
Context: Drug candidates may have atropisomeric axes requiring control and specification.
Example: Atropisomeric biaryl kinase inhibitors.
Related Terms: Axial Chirality, Barrier to Rotation.
Reference: Clayden et al. (2012).
Axial Bond
Definition: A bond directed along the axis of a cyclohexane chair, perpendicular to the mean plane.
Context: Axial substituents experience 1,3-diaxial interactions, strongly influencing conformation and reactivity.
Example: Axial vs equatorial methyl in methylcyclohexane.
Related Terms: Equatorial Bond, A-Values, Conformation.
Reference: Eliel & Wilen (1994).
Axial Chirality
Definition: Chirality arising from hindered rotation about an axis.
Context: Common in biaryls and allenes; impacts ligand and API design.
Example: BINAP, biaryl atropisomers.
Related Terms: Atropisomerism, Helicity.
Reference: IUPAC Gold Book.
Barrier to Rotation (ΔG‡)
Definition: Free-energy barrier that separates enantiomeric conformers/atropisomers.
Context: Determines isolability of atropisomers and labeling requirements.
Example: ΔG‡ > ~25 kcal/mol gives isolable atropisomers at room temperature.
Related Terms: Atropisomerism, Enantiomerization.
Reference: Eliel & Wilen (1994).
Bioactive Conformation
Definition: The conformation adopted by a ligand when bound to its target.
Context: Guides conformational constraint strategies to improve selectivity.
Example: Locked isostere mimicking bound pose.
Related Terms: Conformation, Pharmacophore.
Reference: Silverman (2014).
Bite Angle
Definition: Angle between donor atoms of a bidentate ligand at the metal center.
Context: Modulates enantioselectivity and reactivity in catalytic cycles.
Example: Wide-bite vs narrow-bite diphosphines.
Related Terms: Quadrant Model, Chiral Ligand.
Reference: van Leeuwen, Coordination Chemistry Reviews (1999).
Bürgi–Dunitz Angle
Definition: Preferred trajectory (~107°) of nucleophile approach to a carbonyl.
Context: Rationalizes facial selectivity and reaction rates.
Example: Hydride addition to ketones.
Related Terms: Felkin–Anh, Cram’s Rule.
Reference: Bürgi & Dunitz, JACS (1973).
CBS Reduction
Definition: Corey–Bakshi–Shibata borane reduction of ketones using chiral oxazaborolidines.
Context: Reliable route to enantioenriched alcohols.
Example: CBS reduction of aryl ketones.
Related Terms: Asymmetric Catalysis, Reduction.
Reference: Corey, JACS (1987).
Chelation Control
Definition: Metal coordination overrides Felkin preferences in carbonyl additions.
Context: Explains opposite selectivity in presence of Lewis acids or metals.
Example: Addition to α-alkoxy aldehydes with Mg2+.
Related Terms: Cram’s Rule, Felkin–Anh.
Reference: Reetz, Angew. Chem. (1974).
Chiral
Definition: A geometric property of a molecule or object that is not superimposable on its mirror image.
Context: Chirality is foundational in stereochemistry, determining whether enantiomers exist and influencing pharmacological activity.
Example: Hands are chiral objects; lactic acid has R- and S-enantiomers.
Related Terms: Enantiomer; Chiral Center; Stereoisomer.
Reference: IUPAC. Compendium of Chemical Terminology (IUPAC Gold Book), 2nd Edition, 1997 (updated 2019).
Chiral Auxiliary
Definition: Temporarily attached chiral unit to control stereochemistry of a transformation.
Context: Delivers high selectivity; removed to give target enantioenriched product.
Example: Evans oxazolidinone auxiliaries.
Related Terms: Chiral Pool, Asymmetric Catalysis.
Reference: Evans, JACS (1981).
Chiral Bioequivalence
Definition: Demonstration that enantiomer exposure (AUC, Cmax) is equivalent between products.
Context: Regulatory expectation for racemates and single-enantiomer generics.
Example: Bioequivalence of racemic vs reformulated enantiomer products.
Related Terms: Bioequivalence, FDA Chiral Policy.
Reference: FDA Guidance (2017); FDA 1992 Policy.
Chiral CE (Capillary Electrophoresis)
Definition: Electrophoretic separation with chiral selectors (e.g., cyclodextrins) in the buffer.
Context: High-efficiency analytical separations for enantiomers.
Example: CE of amino acid enantiomers.
Related Terms: Chiral HPLC, CSP.
Reference: Scriba, Electrophoresis (2003).
Chiral Center
Definition: A tetrahedral atom (usually carbon) bonded to four different substituents.
Context: Creates enantiomeric pairs; critical for drug selectivity and metabolism.
Example: The α-carbon of lactic acid.
Related Terms: Stereocenter, Enantiomer.
Reference: IUPAC Gold Book.
Chiral Derivatizing Agent (CDA)
Definition: Enantiomers are converted to diastereomers by reacting with a chiral reagent to enable separation.
Context: Facilitates NMR/LC analysis when direct separation is difficult.
Example: Mosher’s acid chloride (MTPA-Cl).
Related Terms: CDA, Chiral Solvating Agent.
Reference: Mosher, JACS (1973).
Chiral Drug
Definition: A pharmaceutical compound that contains one or more chiral centers or stereogenic elements, existing as enantiomers, diastereomers, or mixtures.
Context: Regulatory and therapeutic implications are critical; one enantiomer may be active (eutomer) while the other may be inactive or harmful (distomer).
Example: Ibuprofen (sold as a racemate, though only the S-enantiomer is pharmacologically active).
Related Terms: Enantiopure; Racemate; Eutomer; Distomer; Stereo-pharmacology.
Reference: FDA. Policy Statement for the Development of New Stereoisomeric Drugs (1992).
Chiral GC (Gas Chromatography)
Definition: GC using chiral stationary phases for volatile enantiomers.
Context: Useful for small, volatile APIs and intermediates.
Example: Resolution of limonene enantiomers.
Related Terms: Chiral HPLC, CE.
Reference: Schurig & Nowotny, J. Chromatogr. A (1990).
Chiral HPLC
Definition: HPLC using chiral stationary phases to separate enantiomers.
Context: Workhorse analytical and preparative method in pharma.
Example: Separation of R/S-propranolol.
Related Terms: CSP, SFC.
Reference: Scriba, J. Chromatogr. A (2016).
Chiral Inversion
Definition: In vivo conversion of one enantiomer to the other.
Context: Impacts dosing and exposure; must be characterized in PK.
Example: R-ibuprofen inverts to S-ibuprofen in humans.
Related Terms: Stereopharmacology, Metabolism.
Reference: Hutt & Caldwell, J. Pharm. Pharmacol. (1983).
Chiral Ligand
Definition: A ligand that induces asymmetry in metal-catalyzed reactions.
Context: Central in enantioselective hydrogenation and C–C bond formation.
Example: BINAP ligand.
Related Terms: Asymmetric Catalysis, Enantioselectivity.
Reference: Noyori, Angew. Chem. (1994).
Chiral Mass Spectrometry
Definition: MS technique combined with chiral derivatization or ion mobility to distinguish enantiomers.
Context: Emerging analytical tool for stereoisomers.
Example: Chiral recognition of amino acids.
Related Terms: MS, Chiral Derivatizing Agents.
Reference: Dwivedi et al., Anal Chem (2006).
Chiral Pharmacology
Definition: The study of how molecular chirality influences pharmacodynamic and pharmacokinetic behavior in biological systems.
Context: Enantiomers often differ in potency, metabolism, and toxicity. Understanding chiral pharmacology is crucial for rational drug development and regulatory approval.
Example: S-warfarin is the more potent anticoagulant enantiomer compared to R-warfarin.
Related Terms: Stereo-pharmacology; Eutomer; Distomer; Enantiomeric Excess.
Reference: Caldwell, J. (1995). Chiral pharmacology and the regulation of new drugs. Chemistry and Industry, 6, 176-179; Hutt, A. J. & Caldwell, J. "The importance of stereochemistry in drug action and disposition." Pharmacology & Therapeutics, 29(2): 245-263 (1985).
Chiral Phosphate Catalysis
Definition: Brønsted acid catalysis using BINOL-derived chiral phosphoric acids.
Context: Broad platform for enantioselective additions and rearrangements.
Example: CPA-catalyzed Mannich reactions.
Related Terms: Organocatalysis, Brønsted Acid Catalysis.
Reference: Akiyama/Terada, Chem. Rev. (2018).
Chiral Photochemistry
Definition: Use of light to induce stereocontrol via chiral catalysts, templates, or circularly polarized light.
Context: Enables unique selectivity pathways and deracemization.
Example: CPL-mediated enantioenrichment.
Related Terms: Asymmetric Catalysis, CPL.
Reference: Bach & Hehn, Angew. Chem. (2011).
Chiral Pool Synthesis
Definition: Use of abundant natural enantiopure building blocks as stereochemical sources.
Context: Efficient, scalable strategy in pharmaceutical synthesis.
Example: Use of L-amino acids to set stereochemistry.
Related Terms: Biocatalysis, Chiral Auxiliary.
Reference: Morrison & Boyd.
Chiral Recognition
Definition: Selective interaction of a host with one enantiomer over the other.
Context: Underlies chiral separations and receptor binding selectivity.
Example: Cyclodextrin inclusion complexes.
Related Terms: Molecular Imprinting, Chiral HPLC.
Reference: Wainer, Drug Discov Today (1997).
Chiral Resolution by Enzymes
Definition: Use of biocatalysts to selectively transform one enantiomer.
Context: Scalable, green alternative to chemical resolution.
Example: Lipase-catalyzed ester hydrolysis.
Related Terms: Biocatalysis, Kinetic Resolution.
Reference: Bornscheuer, Nature (2012).
Chiral SFC (Supercritical Fluid Chromatography)
Definition: Chromatography using supercritical CO? with chiral stationary phases.
Context: Fast, green separations widely adopted for enantioresolution.
Example: Rapid enantiomer separation of β-blockers.
Related Terms: Chiral HPLC, CSP.
Reference: Berger, Supercritical Fluid Chromatography (1995).
Chiral Shift Reagent
Definition: Paramagnetic lanthanide complexes that induce differential NMR shifts for enantiomers.
Context: Legacy technique for stereochemical analysis.
Example: Eu(fod)? added to racemates.
Related Terms: CSA, NMR.
Reference: Günther, NMR Spectroscopy (2013).
Chiral Solvating Agent (CSA)
Definition: Chiral additive forming diastereomeric complexes that resolve NMR signals.
Context: Allows ee determination without derivatization.
Example: Pirkle’s alcohols; TFAE.
Related Terms: CDA, NMR.
Reference: Pirkle, J. Org. Chem. (1967).
Chiral Stationary Phase (CSP)
Definition: Chromatographic phase containing chiral selectors (polysaccharides, cyclodextrins, Pirkle-type, proteins).
Context: Core technology for analytical and preparative enantioseparation.
Example: Cellulose tris(3,5-dimethylphenylcarbamate).
Related Terms: Chiral HPLC, SFC.
Reference: Scriba, J. Chromatogr. A (2016).
Chiral Switch
Definition: Replacing a racemic drug with its single active enantiomer.
Context: Lifecycle and safety strategy improving efficacy and dose control.
Example: Esomeprazole replacing omeprazole.
Related Terms: Eutomer, Stereopharmacology.
Reference: FDA Policy (1992).
Chiral Toxicology
Definition: Study of enantioselective toxicity and safety profiles.
Context: Eutomers and distomers can differ in adverse effects; regulators expect isomer-specific assessment.
Example: S-thalidomide vs R-thalidomide.
Related Terms: Eutomer, Distomer.
Reference: FDA Stereoisomeric Drugs Policy (1992).
Chiral-Induced Spin Selectivity (CISS)
Definition: Phenomenon where electron spin polarization arises during transport through chiral media.
Context: Emerging relevance in bioelectronics and sensing; conceptual interest in drug–protein interactions.
Example: Spin filtering through DNA helices.
Related Terms: Helicity, Chiroptics.
Reference: Naaman & Waldeck, Annu. Rev. Phys. Chem. (2015).
Chirality
Definition: A geometric property where an object or molecule is not superimposable on its mirror image.
Context: Foundational to stereochemistry; chirality determines enantiomer formation and can alter pharmacological profiles.
Example: Hands are chiral; R- and S-lactic acid are mirror images.
Related Terms: Enantiomer, Stereocenter, Stereoisomer.
Reference: IUPAC Gold Book (2019).
CIP Rules
Definition: Priority rules to rank substituents for stereochemical assignment.
Context: Foundation for R/S and E/Z nomenclature across industry and regulation.
Example: Assigning R to lactic acid’s chiral center.
Related Terms: R/S Configuration, E/Z Isomerism.
Reference: Cahn, Ingold & Prelog, Experientia (1956).
Circular Dichroism (CD)
Definition: Difference in absorption of left vs right circularly polarized light.
Context: Key chiroptical method for absolute configuration and secondary structure.
Example: ECD of helicenes; protein far-UV CD.
Related Terms: ECD, VCD, ROA.
Reference: Kelly et al., Biochim. Biophys. Acta (2005).
Circularly Polarized Luminescence (CPL)
Definition: Difference in emission of left vs right circularly polarized light.
Context: Emerging tool for chiral luminophores and bioimaging probes.
Example: CPL of lanthanide complexes.
Related Terms: CD, g-factor.
Reference: Zinna & Di Bari, Chirality (2015).
Configuration
Definition: The fixed spatial arrangement of atoms about a stereogenic element not interconverted without bond breaking.
Context: Configuration defines absolute identity of stereoisomers and must be controlled in pharma.
Example: R vs S configuration at a chiral center.
Related Terms: Absolute Configuration, Relative Configuration.
Reference: IUPAC Gold Book.
Conformation
Definition: Different spatial arrangements generated by rotation about single bonds.
Context: Bioactive conformation often dictates receptor binding and SAR.
Example: Anti vs gauche conformers of butane.
Related Terms: Conformational Isomerism, Bioactive Conformation.
Reference: Clayden et al., Organic Chemistry (2012).
Conformational Constraint
Definition: Structural modification limiting molecular flexibility.
Context: Improves binding affinity and selectivity.
Example: Locked nucleic acids (LNAs).
Related Terms: SAR, Pharmacophore.
Reference: Silverman, Drug Design (2014).
Conformational Isomer (Conformer)
Definition: Isomers differing only by rotation about single σ-bonds without bond breaking.
Context: Conformational analysis is essential in understanding stability, reactivity, and bioactive geometry.
Example: Chair and boat forms of cyclohexane.
Related Terms: Conformer; Conformation; Eclipsed; Gauche.
Reference: Clayden, J., Greeves, N., Warren, S. & Wothers, P. Organic Chemistry. Oxford University Press, 2012.
Conformational Isomerism
Definition: Interconversion between isomers via rotation about σ-bonds.
Context: Conformational preferences control stereochemical outcomes and binding.
Example: Chair vs boat cyclohexane.
Related Terms: Conformation, Stereoelectronic Effect.
Reference: Clayden et al. (2012).
Conformer
Definition: A specific spatial arrangement of atoms in a molecule that can be interconverted by rotation about single bonds.
Context: Conformers represent energetically accessible geometries; populations depend on steric and electronic effects.
Example: Staggered and eclipsed conformations of ethane.
Related Terms: Conformational Isomer; Newman Projection; Gauche; Eclipsed.
Reference: Eliel, E. L. & Wilen, S. H. Stereochemistry of Organic Compounds. Wiley, 1994.
Conglomerate (Racemic Conglomerate)
Definition: Racemic mixture that crystallizes as separate enantiomorphic crystals.
Context: Enables preferential crystallization and Viedma ripening strategies.
Example: Sodium ammonium tartrate behavior.
Related Terms: Racemate, Viedma Ripening.
Reference: Eliel & Wilen (1994).
Cornforth Model
Definition: Predicts anti-selective substitution via antiperiplanar alignment.
Context: Used for 1,3-asymmetric induction analysis.
Example: Allylic substitutions.
Related Terms: Felkin–Anh, Zimmerman–Traxler.
Reference: Cornforth, Chem. Soc. Rev. (1971).
Cotton Effect
Definition: Characteristic sign and magnitude change in CD/ORD near an absorption band.
Context: Diagnostic for electronic transitions and stereochemical assignment.
Example: Positive/negative couplets in aromatic chromophores.
Related Terms: CD, ORD, Exciton Coupling.
Reference: Nakanishi et al. (2007).
Cram’s Rule
Definition: Predicts diastereofacial selectivity based on minimizing steric interactions.
Context: Competes with chelation control in carbonyl additions.
Example: Nucleophile addition to chiral ketones.
Related Terms: Felkin–Anh, Chelation Control.
Reference: Cram, JACS (1952).
Curtin–Hammett Principle
Definition: Product distribution is determined by transition-state energies when conformers interconvert faster than they react.
Context: Explains selectivity in conformationally flexible systems.
Example: Axial/equatorial conformers leading to different products.
Related Terms: Conformation, Kinetics.
Reference: Seeman, Chem. Rev. (1983).
Cyclodextrin CSP
Definition: Cyclodextrin-based selectors suitable for polar and volatile analytes.
Context: Common in CE and GC for small molecules.
Example: β-Cyclodextrin phases.
Related Terms: CSP, Chiral CE/GC.
Reference: Scriba (2003/2016).
D-(Dexter, Right)
Definition: A stereochemical prefix denoting a configuration relative to D-glyceraldehyde, not the direction of optical rotation.
Context: Used in carbohydrate and amino acid nomenclature to define absolute configuration based on Fischer projection.
Example: D-glucose corresponds to the configuration of D-glyceraldehyde.
Related Terms: L-; Fischer Projection; Absolute Configuration.
Reference: Fischer, E. "Einfluss der Configuration auf die Wirkung der Enzyme." Ber. Dtsch. Chem. Ges. 24, 1836-1845 (1891).
Deracemization
Definition: Conversion of a racemic mixture to an enantiopure product without external chiral source.
Context: Strategic for late-stage purification and process intensification.
Example: Viedma ripening, enzymatic deracemization.
Related Terms: Viedma Ripening, Absolute Asymmetric Synthesis.
Reference: Blackmond, Angew. Chem. (2010).
Dextro-(d, +)
Definition: Denotes a compound that rotates plane-polarized light to the right (clockwise).
Context: Optical rotation descriptors are experimental and distinct from R/S configuration.
Example: D-(+)-glucose.
Related Terms: Levo-, Optical Activity, Specific Rotation.
Reference: IUPAC Gold Book.
Diastereomer
Definition: Stereoisomers not related as mirror images.
Context: Often differ in physical properties, enabling separation and selective synthesis.
Example: Erythro vs threo diols.
Related Terms: Enantiomer, Relative Configuration.
Reference: Eliel & Wilen (1994).
Diastereomeric Excess (de)
Definition: Absolute difference between diastereomer fractions.
Context: QC metric when diastereomers are formed.
Example: 80% syn, 20% anti → 60% de.
Related Terms: dr, Stereoselectivity.
Reference: IUPAC Gold Book.
Diastereomeric Ratio (dr)
Definition: Ratio of diastereomers formed in a reaction.
Context: Guides optimization of diastereoselective steps.
Example: 95:5 syn:anti aldol product.
Related Terms: Diastereomeric Excess, Stereoselectivity.
Reference: IUPAC Gold Book.
Distomer
Definition: The enantiomer with lower or undesirable activity.
Context: May contribute to side effects or be removed in development.
Example: R-citalopram.
Related Terms: Eutomer, Racemate.
Reference: Ariëns (1984).
DNA Chirality
Definition: DNA adopts right-handed helices (B-form) with chiral sugar backbone.
Context: Chiral recognition of intercalators and drugs depends on helix sense.
Example: D-sugar backbone in nucleic acids.
Related Terms: Helicity, Stereorecognition.
Reference: Watson & Crick; Voet & Voet (2011).
Double Stereodifferentiation
Definition: Outcome determined by interaction of substrate and reagent chirality (matched/mismatched).
Context: Critical in planning complex multi-stereocenter syntheses.
Example: Aldol with chiral enolate and chiral aldehyde.
Related Terms: Matched/Mismatched, Stereocontrol.
Reference: Seebach (1979).
Dynamic Kinetic Asymmetric Transformation (DYKAT)
Definition: Asymmetric reaction converting a racemic substrate mixture to a single enantiomer product via equilibration.
Context: Converts racemic starting materials fully to one enantiomer product.
Example: Pd-catalyzed allylic substitutions.
Related Terms: DKR, Enantioconvergent Synthesis.
Reference: Kagan, Acc. Chem. Res. (1997).
Dynamic Kinetic Resolution (DKR)
Definition: Resolution combined with in situ racemization to yield >50% of the desired enantiomer.
Context: Boosts efficiency in API synthesis.
Example: Lipase DKR of secondary alcohols.
Related Terms: Kinetic Resolution, DYKAT.
Reference: Pellissier, Tetrahedron (2003).
Dynamic NMR (DNMR)
Definition: NMR methods to study exchange processes and barriers (e.g., enantiomerization).
Context: Quantifies ΔG‡ for atropisomer interconversion relevant to stability.
Example: DNMR of hindered biaryls.
Related Terms: Barrier to Rotation, Enantiomerization.
Reference: Sandström, Dynamic NMR (1982).
E-(Entgegen)
Definition: A geometric descriptor from the Cahn-Ingold-Prelog (CIP) system indicating that the higher-priority substituents on a double bond are on opposite sides.
Context: Used to describe configuration in alkenes and similar systems; "E" is the opposite of "Z."
Example: E-2-butene has methyl groups on opposite sides of the C=C bond.
Related Terms: Z-; Geometric Isomerism; CIP Rules.
Reference: Cahn, R. S., Ingold, C. K. & Prelog, V. "Specification of Molecular Chirality." Angewandte Chemie International Edition 5, 385-415 (1966).
E/Z Isomerism
Definition: Configuration around a double bond assigned by CIP priorities.
Context: Geometry influences potency, selectivity, and metabolism.
Example: E- vs Z-tamoxifen.
Related Terms: Geometric Isomerism, CIP Rules.
Reference: IUPAC Gold Book.
Eclipsed Conformation
Definition: A conformation where substituents on adjacent carbons align with each other, maximizing torsional strain.
Context: Less stable than staggered arrangements due to electron repulsion.
Example: Eclipsed ethane has higher energy than the staggered form.
Related Terms: Conformer; Gauche; Torsional Strain.
Reference: Eliel & Wilen (1994).
Electronic Circular Dichroism (ECD)
Definition: CD arising from electronic transitions.
Context: Used for exciton coupling analysis and absolute configuration of chromophoric systems.
Example: Exciton couplet in BINOL derivatives.
Related Terms: Exciton Coupling, Cotton Effect.
Reference: Nakanishi et al., Circular Dichroism (2007).
Enamine Catalysis
Definition: Organocatalytic activation of carbonyls via enamine intermediates.
Context: Controls enantioface selectivity in additions.
Example: Proline-catalyzed aldol.
Related Terms: Organocatalysis, Iminium Catalysis.
Reference: List/Barbas (2000).
Enantioconvergent Synthesis
Definition: Both enantiomers of a racemic starting material are transformed into one enantiomeric product.
Context: Maximizes material economy in process chemistry.
Example: Ni-catalyzed cross-couplings with stereoretention.
Related Terms: DYKAT, Stereoretentive Coupling.
Reference: Fu, Acc. Chem. Res. (2017).
Enantiomer
Definition: One of a pair of non-superimposable mirror-image stereoisomers.
Context: Enantiomers may differ in PK/PD and toxicity; single-enantiomer drugs are often preferred.
Example: S-ibuprofen (eutomer) vs R-ibuprofen (distomer).
Related Terms: Racemate, Eutomer, Distomer.
Reference: Morrison & Boyd, Organic Chemistry.
Enantiomeric Excess (ee)
Definition: The absolute difference in enantiomer fractions (|%R − %S|).
Context: Standard QC metric for chiral purity in pharma.
Example: 70% R, 30% S → 40% ee.
Related Terms: Enantiomeric Ratio, Optical Purity.
Reference: IUPAC Gold Book.
Enantiomeric Ratio (er)
Definition: The ratio of enantiomers, typically expressed as R:S.
Context: Preferred over ee for statistical modeling and kinetics.
Example: 98:2 e.r. for a product.
Related Terms: Enantiomeric Excess, dr.
Reference: IUPAC Gold Book.
Enantiomerization
Definition: Interconversion between enantiomers via bond rotation or reversible processes.
Context: Defines shelf-life and handling conditions for atropisomeric drugs.
Example: Biaryl axis rotation over barrier ΔG‡.
Related Terms: Racemization, Barrier to Rotation.
Reference: IUPAC Gold Book.
Enantioselective Metabolism
Definition: Metabolic pathways that preferentially process one enantiomer.
Context: Causes distinct clearance and exposure for enantiomers.
Example: CYP-mediated oxidation of one enantiomer faster than the other.
Related Terms: Stereopharmacology, Chiral Inversion.
Reference: Testa & Krämer, Drug Metabolism (2008).
Enantioselectivity
Definition: Preference for formation of one enantiomer over the other (quantified as ee or er).
Context: Primary performance metric in asymmetric synthesis and catalysis.
Example: 98:2 e.r. in asymmetric hydrogenation.
Related Terms: Stereoselectivity, Enantiospecificity.
Reference: Noyori, Nobel Lecture (2001).
Enantiospecificity
Definition: A reaction in which the enantiomeric identity of the product is determined by that of the starting material.
Context: Key in stereoretentive cross-couplings and biosynthetic steps.
Example: Stereoretentive substitution maintaining configuration.
Related Terms: Stereospecificity, Enantioselectivity.
Reference: IUPAC Gold Book.
Enantiotopic
Definition: Two groups or faces of a molecule that become enantiomers upon substitution or reaction.
Context: Differentiated in chiral environments such as enzymatic systems or asymmetric catalysts.
Example: The two hydrogens of methylene in ethanol are enantiotopic.
Related Terms: Diastereotopic; Prochirality; Re/Si Face.
Reference: IUPAC Gold Book (2019).
Epimer
Definition: Diastereomers differing in configuration at only one stereocenter.
Context: Widespread in sugar chemistry and biologically relevant isomers.
Example: D-glucose vs D-mannose (C2 epimers).
Related Terms: Anomer, Diastereomer.
Reference: IUPAC Gold Book.
Equatorial Bond
Definition: A bond directed outward from the equator of a cyclohexane ring, approximately in the ring plane.
Context: Equatorial positions minimize steric hindrance; preferred by bulky substituents.
Example: Equatorial t-Bu in tert-butylcyclohexane.
Related Terms: Axial Bond, Conformation, A-Values.
Reference: Eliel & Wilen (1994).
Erythro-
Definition: A relative stereochemical descriptor for diastereomers with two adjacent chiral centers having substituents on the same side in a Fischer projection.
Context: Commonly used for sugars and amino acids; denotes visual similarity to erythrose.
Example: Erythro-2,3-butanediol has hydroxyl groups on the same side.
Related Terms: Threo-; Relative Configuration; Diastereomer.
Reference: Eliel, E. L. & Wilen, S. H. Stereochemistry of Organic Compounds. Wiley, 1994.
Eudismic Ratio
Definition: The ratio of pharmacological activity of the eutomer (more active enantiomer) to the distomer.
Context: Quantifies the stereochemical contribution to drug action, guiding chiral switch strategies.
Example: S-citalopram vs R-citalopram potency ratio.
Related Terms: Eutomer, Distomer, Stereopharmacology.
Reference: Ariëns, Med. Res. Rev. (1984).
Eutomer
Definition: The enantiomer with the desired higher biological activity.
Context: Target of development and commercialization.
Example: S-citalopram.
Related Terms: Distomer, Chiral Switch.
Reference: Ariëns, Med. Res. Rev. (1984).
Exciton Chirality Method
Definition: Assigns absolute configuration from sign of ECD exciton couplets between interacting chromophores.
Context: Widely applied to biaryls and helicenes.
Example: Positive couplet → P helicity.
Related Terms: ECD, Exciton Coupling.
Reference: Harada & Nakanishi (1972).
Exciton Coupling
Definition: Interaction between transition dipoles of nearby chromophores causing split CD signals.
Context: Exciton-chirality method assigns absolute configuration in biaryl and helicene systems.
Example: Couplet sign in BINOL indicating axial chirality sense.
Related Terms: ECD, Cotton Effect.
Reference: Harada & Nakanishi, Acc. Chem. Res. (1972).
Felkin–Anh Model
Definition: Predicts nucleophilic attack on carbonyls favoring approach anti to the largest substituent.
Context: Standard model for 1,2-asymmetric induction.
Example: Addition to α-chiral aldehydes.
Related Terms: Cram’s Rule, Bürgi–Dunitz Angle.
Reference: Anh & Felkin, Tetrahedron Lett. (1973).
Fischer Projection
Definition: A 2D representation where horizontal lines indicate bonds projecting forward and vertical lines project backward.
Context: Standard tool in carbohydrate and amino acid stereochemistry.
Example: D-glucose drawn in Fischer projection.
Related Terms: Newman Projection, Sawhorse Projection.
Reference: Fischer, Ber. Dtsch. Chem. Ges. (1891).
Flack Parameter (x)
Definition: Refinement parameter indicating correct absolute structure in X-ray crystallography.
Context: x ~ 0 confirms correct absolute configuration; x ~ 1 suggests inversion.
Example: Reporting Flack x for a chiral API crystal.
Related Terms: Absolute Configuration, X-ray Crystallography.
Reference: Flack, Acta Cryst. A (1983).
Gauche
Definition: A conformation in which substituents on adjacent carbons are separated by a dihedral angle of approximately 60°.
Context: Important in determining conformational energy and intramolecular interactions such as the gauche effect.
Example: Gauche butane conformation is less stable than anti but more stable than eclipsed.
Related Terms: Anti; Synclinal; Conformation; Newman Projection.
Reference: Eliel & Wilen (1994).
Geminal
Definition: Refers to two substituents attached to the same atom, typically a carbon.
Context: Geminal dihalides or diols exhibit distinct reactivity compared to vicinal analogs.
Example: Geminal dichlorides (R2CCl2) vs vicinal dichlorides (RCHCl-CH2Cl).
Related Terms: Vicinal; Substituent; Structural Isomer.
Reference: IUPAC Gold Book (2019).
Geometric Isomerism
Definition: Stereoisomerism due to restricted rotation (double bonds, rings).
Context: Controls pharmacology through spatial disposition of groups.
Example: cis/trans-platin complexes.
Related Terms: E/Z Isomerism, Ring Conformations.
Reference: IUPAC Gold Book.
GPCR Stereoselectivity
Definition: Enantiomer-dependent binding and signaling at GPCRs.
Context: Explains potency and bias differences across enantiomers.
Example: L- vs D-ligands at opioid receptors.
Related Terms: Stereopharmacology, Eutomer/Distomer.
Reference: Kenakin, Pharmacology Primer (2019).
Hashed (Wedge-Dash Representation)
Definition: A visual notation in molecular drawings where hashed bonds represent bonds going behind the plane of the paper.
Context: Used to depict stereochemistry in three-dimensional projections.
Example: Hashed bond to indicate the backward substituent in Fischer or wedge projections.
Related Terms: Wedged; Fischer Projection; Newman Projection.
Reference: Morrison & Boyd. Organic Chemistry. Prentice Hall, 1992.
Helicity (P/M)
Definition: Screw sense of helical molecules designated P (plus) or M (minus).
Context: Describes helicenes and protein helices relevant to binding.
Example: P-helicene vs M-helicene.
Related Terms: Axial Chirality, Planar Chirality.
Reference: IUPAC Gold Book.
Horeau Method
Definition: Indirect determination of ee via formation of meso/dl diesters.
Context: Historical approach for ee estimation.
Example: Horeau’s diacid anhydrides with alcohols.
Related Terms: Optical Purity, CDA.
Reference: Horeau, Tetrahedron (1961).
Iminium Catalysis
Definition: Activation of α,β-unsaturated carbonyls via chiral iminium ions.
Context: Enables enantioselective Michael additions and cycloadditions.
Example: MacMillan catalysts.
Related Terms: Organocatalysis, Enamine Catalysis.
Reference: MacMillan, Nature (2000).
Isomer
Definition: A compound that shares the same molecular formula with another compound but differs in atomic connectivity or spatial arrangement.
Context: Isomers are classified into structural (constitutional) and stereoisomers, including enantiomers and diastereomers.
Example: Butane and isobutane are constitutional isomers; R- and S-lactic acid are enantiomers.
Related Terms: Isomerism; Stereoisomer; Constitutional Isomer.
Reference: IUPAC. Compendium of Chemical Terminology (IUPAC Gold Book), 2nd Edition, 1997 (updated 2019).
Isomeric Ballast
Definition: Non-pharmacologically active stereoisomeric portion of a racemic or stereoisomeric drug mixture.
Context: Regulatory agencies require understanding of ballast contribution to safety and efficacy.
Example: R-ibuprofen considered ballast in S-ibuprofen therapy.
Related Terms: Distomer, Racemate, Stereo-pharmacology.
Reference: Ariëns, Med. Res. Rev. (1986).
Isomeric Purity Specification
Definition: Quality specification defining acceptable levels of undesired stereoisomers.
Context: ICH Q6A expects justified limits for isomers with safety/efficacy impact.
Example: Limit of ≤0.5% distomer in eutomer API.
Related Terms: ICH Q6A, QC.
Reference: ICH Q6A (1999).
Isomerism
Definition: The phenomenon in which compounds share the same molecular formula but differ in structure or spatial arrangement.
Context: Forms the basis of structural and stereochemical diversity in organic and medicinal chemistry.
Example: Ethanol and dimethyl ether are structural isomers; cis- and trans-2-butene are geometric isomers.
Related Terms: Isomer; Stereoisomer; Constitutional Isomer; Enantiomer; Diastereomer.
Reference: IUPAC. Compendium of Chemical Terminology (IUPAC Gold Book), 2nd Edition, 1997 (updated 2019).
Jacobsen–Katsuki Epoxidation
Definition: Mn–salen-catalyzed asymmetric epoxidation of unfunctionalized alkenes.
Context: Expands epoxidation to substrates beyond allylic alcohols.
Example: Epoxidation of styrenes.
Related Terms: Asymmetric Catalysis, Epoxidation.
Reference: Jacobsen, JACS (1990/1991).
Kagan ML? Model
Definition: Model rationalizing nonlinear ee effects via homochiral/heterochiral catalyst aggregates.
Context: Guides interpretation of catalyst behavior in development.
Example: Dimeric catalyst equilibria giving nonlinear plots.
Related Terms: Nonlinear Effects, Enantioselectivity.
Reference: Kagan, Acc. Chem. Res. (1997).
Karplus Relationship
Definition: Empirical relationship between vicinal ³J coupling and dihedral angle.
Context: Supports stereochemical assignment from NMR coupling constants.
Example: ³JHH ~ 10 Hz for anti arrangement.
Related Terms: J-Coupling, Conformation.
Reference: Karplus, J. Chem. Phys. (1959).
L-(Laevus, Left)
Definition: A stereochemical prefix denoting configuration opposite to that of D-glyceraldehyde, based on the Fischer projection.
Context: Indicates mirror-image relationship to D-forms; unrelated to optical rotation (d/l).
Example: L-alanine corresponds to the configuration of L-glyceraldehyde.
Related Terms: D-; Fischer Projection; Absolute Configuration.
Reference: Fischer (1891).
Levo- (l, –)
Definition: Denotes a compound that rotates plane-polarized light to the left (counter-clockwise).
Context: Paired with dextro-; unrelated to R/S assignment.
Example: L-(–)-lactic acid.
Related Terms: Dextro-, Optical Activity, Specific Rotation.
Reference: IUPAC Gold Book.
Matched Pair
Definition: Substrate and chiral reagent/catalyst whose stereochemical preferences reinforce each other.
Context: Delivers higher selectivity than mismatched combinations.
Example: (S)-substrate with (S)-auxiliary.
Related Terms: Mismatched Pair, Double Stereodifferentiation.
Reference: Seebach, Angew. Chem. (1979).
Memory of Chirality
Definition: Retention of stereochemical information through achiral or planar intermediates via conformational constraints.
Context: Enables net stereospecificity where racemization might be expected.
Example: Acylium ion cyclizations retaining chirality.
Related Terms: Stereomutation, Enantiospecificity.
Reference: Houk, Angew. Chem. (2001).
Meso Compound
Definition: An achiral molecule with stereocenters and an internal plane/center of symmetry.
Context: No net optical activity, important in planning stereoselective routes.
Example: Meso-tartaric acid.
Related Terms: Symmetry, Diastereomer.
Reference: Eliel & Wilen (1994).
Meso-
Definition: A molecule containing stereocenters but overall achiral due to an internal plane or center of symmetry.
Context: Meso compounds are optically inactive even though they contain chiral atoms.
Example: Meso-tartaric acid.
Related Terms: Achiral; Symmetry; Diastereomer.
Reference: Eliel & Wilen (1994).
Mismatched Pair
Definition: Substrate and chiral reagent/catalyst with opposing preferences.
Context: Reduces stereoselectivity; addressed by switching catalyst or substrate.
Example: (S)-substrate with (R)-auxiliary.
Related Terms: Matched Pair, Stereoselectivity.
Reference: Evans, JACS (1981).
Molar Rotation (Φ)
Definition: Specific rotation multiplied by molar mass.
Context: Allows comparison of chiroptical responses across compounds.
Example: Molar rotation trends within homologous series.
Related Terms: Specific Rotation, Optical Activity.
Reference: Barron, Molecular Light Scattering (2004).
Molecular Imprinting
Definition: Template-directed polymerization producing cavities complementary to a target enantiomer.
Context: Creates synthetic receptors for separations and sensing.
Example: Imprinted polymers for S-propranolol.
Related Terms: Chiral Recognition, CSP.
Reference: Sellergren, Chem. Rev. (2000).
Mosher’s Method
Definition: Use of MTPA esters/amides to assign absolute configuration by Δδ patterns.
Context: Gold-standard for alcohols and amines in small-molecule analysis.
Example: Δδ analysis of secondary alcohols.
Related Terms: CDA, NMR.
Reference: Dale & Mosher, JACS (1973).
Neighboring Group Participation (NGP)
Definition: Assistance by an adjacent group forming bridged intermediates that alter stereochemical outcome.
Context: Can cause retention or special selectivity in substitutions.
Example: Participation by acetoxy in solvolysis.
Related Terms: SN1, SN2.
Reference: March, Advanced Organic Chemistry (2007).
Newman Projection
Definition: A perspective representation viewing along a C–C bond, useful for analyzing conformations.
Context: Widely used in stereo-electronic analysis and to visualize torsional strain.
Example: Staggered vs eclipsed ethane conformations.
Related Terms: Sawhorse Projection, Conformation.
Reference: Newman, JACS (1952).
NOE/NOESY
Definition: Nuclear Overhauser effect experiments probing through-space proximities.
Context: Establishes relative configuration and conformation.
Example: NOESY on cyclic diols.
Related Terms: J-Coupling, ROESY.
Reference: Claridge, High-Resolution NMR (2009).
Nonlinear Effects in Asymmetric Catalysis
Definition: Nonlinear relationship between catalyst ee and product ee due to catalyst aggregation or kinetics.
Context: Impacts process scale-up and control strategies.
Example: Kagan’s ML? model.
Related Terms: Kagan Model, Enantioselectivity.
Reference: Kagan & Blackmond, Acc. Chem. Res. (2000).
Noyori Hydrogenation
Definition: Asymmetric hydrogenation via bifunctional Ru/diamine catalysts.
Context: Industrial method for enantioenriched alcohols and amines.
Example: Hydrogenation of ketones with Ru-BINAP/diamine.
Related Terms: Asymmetric Catalysis, Transfer Hydrogenation.
Reference: Noyori, Angew. Chem. (1994/2001).
Oppolzer Sultam
Definition: A rigid chiral auxiliary derived from camphor used to control facial selectivity.
Context: Useful for Diels–Alder and alkylation reactions with high selectivity.
Example: Sultam-controlled cycloadditions.
Related Terms: Chiral Auxiliary, Asymmetric Synthesis.
Reference: Oppolzer, Tetrahedron (1987).
Optical Activity
Definition: Rotation of plane-polarized light by chiral substances.
Context: Classical signature of chirality; still used for QC when specific rotation is compendial.
Example: [α]D^20 measurements for amino acids.
Related Terms: Polarimetry, Specific Rotation.
Reference: Atkins, Physical Chemistry.
Optical Activity
Definition: The ability of chiral substances to rotate the plane of polarized light.
Context: Classical indicator of chirality; measured via polarimetry to assess enantiomeric purity.
Example: (+)-Lactic acid rotates plane-polarized light to the right.
Related Terms: Optical Rotation; Specific Rotation; Polarimetry.
Reference: Atkins, P. W. Physical Chemistry. Oxford University Press, 2010.
Optical Purity
Definition: Measured enantiomeric purity derived from specific rotation relative to a pure enantiomer.
Context: Historical measure that correlates with ee when linear.
Example: Optical purity ≈ ee for simple systems.
Related Terms: Enantiomeric Excess, Polarimetry.
Reference: Morrison & Boyd.
Optical Rotation
Definition: The observed angle by which plane-polarized light is rotated upon passing through a chiral sample.
Context: Dependent on path length, concentration, wavelength, and temperature; denoted [α]D20.
Example: [α]D20 = +12.5° (c 1.0, MeOH).
Related Terms: Optical Activity; Specific Rotation; Polarimetry.
Reference: USP-NF General Chapter <781> Optical Rotation.
Optical Rotatory Dispersion (ORD)
Definition: Wavelength dependence of optical rotation.
Context: Precursor to CD; used for stereochemical assignment and conformational analysis.
Example: ORD curves distinguishing sugar stereoisomers.
Related Terms: Circular Dichroism, Cotton Effect.
Reference: Lightner & Gurst, Organic Conformational Analysis (1980).
Organocatalysis
Definition: Enantioselective catalysis with small organic molecules.
Context: Metal-free, green, and scalable approaches for key stereogenic steps.
Example: Proline-catalyzed aldol reactions.
Related Terms: Iminium Catalysis, Enamine Catalysis.
Reference: List & Barbas, JACS (2000).
Phase-Transfer Catalysis (PTC)
Definition: Biphasic catalysis moving anions across phases with chiral quaternary ammonium salts.
Context: Practical for large-scale enantioselective alkylations.
Example: Cinchona-derived PTCs.
Related Terms: Organocatalysis, Asymmetric Catalysis.
Reference: Starks, JACS (1971); O’Donnell, Acc. Chem. Res. (2004).
Pirkle-Type CSP
Definition: Small-molecule chiral selectors relying on π–π and H-bond interactions.
Context: Versatile for aromatic enantiomers and drug-like molecules.
Example: Whelk-O columns.
Related Terms: CSP, Chiral HPLC.
Reference: Pirkle, J. Chromatogr. (1981).
Planar Chirality
Definition: Chirality resulting from the arrangement of substituents in a plane.
Context: Seen in ferrocene ligands and metallocenes used in asymmetric catalysis.
Example: Planar-chiral 1,2-disubstituted ferrocenes.
Related Terms: Helicity, Axial Chirality.
Reference: IUPAC Gold Book.
Polarimetry
Definition: Technique to measure optical rotation of chiral compounds.
Context: Rapid QC screen for enantiomeric composition when correlation is established.
Example: Measuring rotation of limonene enantiomers.
Related Terms: Optical Activity, Specific Rotation.
Reference: Atkins, Physical Chemistry.
Polysaccharide CSP
Definition: Derivatized cellulose/amylose selectors coated or immobilized on silica.
Context: Most widely used CSPs due to broad applicability.
Example: Chiralcel OD-H equivalents.
Related Terms: CSP, Chiral HPLC.
Reference: Okamoto, Chem. Rev. (2011).
Pro-R / Pro-S
Definition: Labels for enantiotopic groups whose replacement would give R or S product.
Context: Critical in enzymatic selectivity and NMR assignment.
Example: Pro-R hydrogen abstraction in alcohol dehydrogenase.
Related Terms: Prochirality, Re/Si Face.
Reference: IUPAC Gold Book.
Prochirality
Definition: An achiral entity that can become chiral by a single desymmetrizing step.
Context: Basis for enantioface/enantioselective reactions in synthesis and enzymology.
Example: Prochiral ketones undergoing enantioselective reduction.
Related Terms: Re/Si Face, Pro-R/Pro-S.
Reference: IUPAC Gold Book.
Protein Homochirality
Definition: Proteins are composed almost exclusively of L-amino acids.
Context: Drives stereoselective binding and metabolism in biology.
Example: Enzymes discriminating D- vs L-substrates.
Related Terms: Homochirality, Stereorecognition.
Reference: Blackmond, PNAS (2004).
Pseudoasymmetric Center (r/s)
Definition: A stereocenter whose configuration is defined relative to other stereocenters (lowercase r/s).
Context: Relevant in complex APIs where relayed stereochemistry affects labeling.
Example: r/s descriptors in substituted tartaric acid derivatives.
Related Terms: CIP Rules, Relative Configuration.
Reference: IUPAC Gold Book.
Quadrant Model (Hydrogenation)
Definition: Empirical model mapping steric quadrants around metal–ligand catalysts to predict facial selectivity.
Context: Used with Rh-DuPHOS, BINAP-Ru systems for enantioface control.
Example: Asymmetric hydrogenation of dehydroamino acids.
Related Terms: Bite Angle, Chiral Ligand.
Reference: Knowles/Halpern analyses (1970s–1990s).
R/S Configuration
Definition: CIP-based descriptors assigning absolute configuration to stereocenters.
Context: Universal language for stereochemical specification in pharma and patents.
Example: S-ibuprofen is the active eutomer.
Related Terms: CIP Rules, Absolute Configuration.
Reference: Cahn–Ingold–Prelog rules (1956/1966).
Racemate (rac)
Definition: A 1:1 mixture of enantiomers.
Context: Common synthetic outcome; may require resolution or chiral switching.
Example: Racemic thalidomide.
Related Terms: Conglomerate, Racemic Compound.
Reference: FDA Policy on Stereoisomeric Drugs (1992).
Racemic Compound
Definition: Racemate that crystallizes as a single racemic crystal containing both enantiomers.
Context: Limits simple preferential crystallization; requires alternative resolution routes.
Example: Racemic mandelic acid (context dependent).
Related Terms: Racemate, Conglomerate.
Reference: Eliel & Wilen (1994).
Racemization
Definition: Conversion of an enantiopure substance to a racemate.
Context: Critical risk for chiral APIs and must be controlled in process/storage.
Example: Base-catalyzed racemization of α-chiral carbonyls.
Related Terms: Enantiomerization, Stereomutation.
Reference: IUPAC Gold Book.
Raman Optical Activity (ROA)
Definition: Difference in Raman scattering for circularly polarized light.
Context: Complementary to VCD; sensitive to conformation of chiral molecules and biomacromolecules.
Example: ROA of proteins to assess secondary structure.
Related Terms: VCD, CD.
Reference: Barron, Molecular Light Scattering (2004).
Re/Si Face
Definition: Descriptors for the two faces of a trigonal (sp²) center.
Context: Used to define enantioface selectivity in additions and reductions.
Example: Hydride attack on the Re face of a ketone.
Related Terms: Prochirality, Pro-R/Pro-S.
Reference: IUPAC Gold Book.
Relative Configuration
Definition: The spatial relationship between stereocenters within a molecule without reference to absolute R/S.
Context: Useful for assigning diastereomer series in synthesis and NMR analysis.
Example: Erythro vs threo in sugars.
Related Terms: Diastereomer, Absolute Configuration.
Reference: Eliel & Wilen (1994).
Relative Stereochemistry
Definition: The spatial relationship between stereocenters within a molecule without reference to absolute configuration.
Context: Important for describing diastereomers in synthesis and structure elucidation.
Example: Erythro and threo configurations of 2,3-butanediols.
Related Terms: Absolute Configuration; Diastereomer; Enantiomer.
Reference: Eliel & Wilen (1994).
Resolution
Definition: The process of separating a racemic mixture into its individual enantiomers.
Context: A key step in the preparation of enantiopure compounds for pharmaceutical use. Can be achieved through crystallization, chemical or enzymatic methods, or chiral chromatography.
Example: Resolution of racemic mandelic acid using (+)-α-phenylethylamine.
Related Terms: Racemate; Enantiomeric Excess; Chiral HPLC; Kinetic Resolution.
Reference: Jacques, J., Collet, A. & Wilen, S. H. Enantiomers, Racemates, and Resolutions. Wiley, 1981.
Sawhorse Projection
Definition: Representation of conformations showing a C–C bond diagonally with attached substituents.
Context: Useful for depicting stereochemical relationships and conformational preferences.
Example: Anti vs gauche butane.
Related Terms: Newman Projection, Conformation.
Reference: Eliel & Wilen (1994).
Scalemic Mixture
Definition: A mixture with unequal amounts of enantiomers (non-racemic).
Context: Describes real-world batches before final enantiopurification and specifications.
Example: 90:10 e.r. mixture of a chiral API.
Related Terms: Enantiomeric Excess, Racemate.
Reference: IUPAC Gold Book.
Sharpless Dihydroxylation
Definition: OsO4/ligand (AD-mix) enantioselective dihydroxylation of alkenes.
Context: Delivers vic-diols with predictable configuration.
Example: AD-mix-α/β applications.
Related Terms: Sharpless Epoxidation, Asymmetric Catalysis.
Reference: Sharpless (2001).
Sharpless Epoxidation
Definition: Ti–tartrate-catalyzed enantioselective epoxidation of allylic alcohols.
Context: Workhorse method to install epoxides with high ee.
Example: Epoxidation to epothilone intermediates.
Related Terms: Asymmetric Catalysis, Sharpless Dihydroxylation.
Reference: Sharpless, Nobel Lecture (2001).
SN1 Racemization
Definition: Loss of configuration due to planar carbocation intermediate in SN1 reactions.
Context: Explains partial/complete racemization in solvolysis.
Example: Solvolysis of tert-butyl chloride.
Related Terms: SN1, Neighboring Group Participation.
Reference: Morrison & Boyd.
Soai Reaction
Definition: Asymmetric autocatalysis of pyrimidyl alkanol formation showing amplification from minute ee.
Context: Model system for origin-of-homochirality studies.
Example: Autocatalytic addition of diisopropylzinc to aldehydes.
Related Terms: Absolute Asymmetric Synthesis, Amplification.
Reference: Soai, Nature (1995).
Solid Solution (Racemic Solid Solution)
Definition: Crystalline phase where enantiomers are disordered over lattice sites.
Context: Challenging for resolution; may impact solid-state specifications.
Example: Racemic mixtures forming solid solutions.
Related Terms: Racemic Compound, Conglomerate.
Reference: Eliel & Wilen (1994).
Specific Rotation ([α]λ^T)
Definition: Observed optical rotation normalized to concentration and path length.
Context: Compendial test for chiral purity/identity in some monographs.
Example: [α]D^20 = +12.5 (c 1.0, MeOH).
Related Terms: Optical Activity, Polarimetry.
Reference: USP/Ph. Eur. General Chapters.
Spiranes
Definition: Bicyclic systems sharing a single atom; may be chiral without stereocenters.
Context: Offer rigid, 3D scaffolds for medicinal chemistry.
Example: Spiro[4.4]nonane derivatives.
Related Terms: Topological Chirality, Planar Chirality.
Reference: Clayden et al. (2012).
Stereocenter
Definition: An atom at which interchange of two substituents produces a stereoisomer.
Context: Defines loci of stereochemical variation and controls stereochemical outcomes in synthesis.
Example: Tetrahedral carbon with four different substituents.
Related Terms: Chiral Center, Stereogenic Center.
Reference: IUPAC Gold Book.
Stereochemistry
Definition: The branch of chemistry concerned with the three-dimensional arrangement of atoms in molecules and its influence on properties and reactions.
Context: Central to understanding drug action, synthesis outcomes, and regulatory specifications for isomeric purity.
Example: E/Z isomers of tamoxifen show distinct properties.
Related Terms: Chirality, Configuration, Conformation.
Reference: Eliel & Wilen (1994).
Stereodivergent Synthesis
Definition: Strategy enabling access to multiple stereoisomers via controlled catalyst/condition changes.
Context: Efficient generation of stereochemical arrays for SAR.
Example: Catalyst-controlled divergent aldol products.
Related Terms: Enantiodivergence, Diastereodivergence.
Reference: Wang & List, Angew. Chem. (2012).
Stereoelectronic Effect
Definition: Effect of orbital alignment on conformation and reactivity.
Context: Controls anomeric effect, β-elimination geometry, and selectivity.
Example: Anomeric effect in carbohydrates.
Related Terms: Antiperiplanar, Hyperconjugation.
Reference: Deslongchamps, Stereoelectronic Effects (1983).
Stereogenic Axis (Axis of Chirality)
Definition: A linear element in a molecule that gives rise to chirality due to restricted rotation.
Context: Common in atropisomeric systems and cumulenes like allenes.
Example: Axially chiral biaryl ligands such as BINAP.
Related Terms: Atropisomerism; Axial Chirality; Planar Chirality.
Reference: IUPAC Gold Book (2019).
Stereogenic Center
Definition: An atom at which the interchange of two substituents generates a stereoisomer.
Context: Most often a tetrahedral carbon with four different substituents; key determinant of chirality in drugs.
Example: The α-carbon in lactic acid is a stereogenic center
Related Terms: Chiral Center; Stereocenter; Enantiomer.
Reference: IUPAC. Compendium of Chemical Terminology (IUPAC Gold Book), 2nd Edition, 1997 (updated 2019).
Stereogenic Element
Definition: Any structural feature (center, axis, plane, helix) that generates stereoisomerism.
Context: Extends chirality beyond tetrahedral centers to axes and planes common in drugs and ligands.
Example: Axial chirality in BINAP; planar chirality in ferrocene.
Related Terms: Axial Chirality, Planar Chirality, Helicity.
Reference: IUPAC Gold Book.
Stereoisomer(s)
Definition: Compounds with the same molecular formula and bonding sequence but differing in three-dimensional arrangement.
Context: Includes enantiomers and diastereomers, fundamental to stereochemistry and pharmacology.
Example: Cis/trans isomers of 2-butene; R- and S-lactic acid.
Related Terms: Enantiomer; Diastereomer; Isomerism.
Reference: IUPAC Gold Book (2019).
Stereomutation
Definition: Interconversion between stereoisomers (e.g., enantiomerization, epimerization).
Context: Impacts shelf life and bioactivity; must be profiled in stability studies.
Example: Atropisomer interconversion over time.
Related Terms: Racemization, Barrier to Rotation.
Reference: Clayden et al. (2012).
Stereopharmacology (Stereo-pharmacology)
Definition: Discipline examining how stereochemistry affects pharmacodynamics and pharmacokinetics.
Context: Guides selection of the optimal enantiomer and specification of isomeric purity.
Example: Chiral switch from omeprazole to esomeprazole.
Related Terms: Eutomer/Distomer, Chiral Inversion.
Reference: Spasov A.A., Iiezhitsa I.N. [Stereopharmacology of carnitine]. Ross Fiziol Zh Im I M Sechenova. 2005, 91(12):1469-1480. Russian. PMID: 16493928.
Stereoselective Binding
Definition: Preferential binding of one stereoisomer to a chiral target.
Context: Directly affects potency, efficacy, and safety.
Example: One enantiomer with higher affinity to an enzyme active site.
Related Terms: Chiral Recognition, Stereopharmacology.
Reference: Silverman, Drug Design (2014).
Stereoselective Transport
Definition: Transporters recognizing one enantiomer with higher affinity.
Context: Affects absorption/distribution differences between enantiomers.
Example: OATP transport of certain eutomer predominates.
Related Terms: Stereopharmacology, Pharmacokinetics.
Reference: Giacomini et al., Nat. Rev. Drug Discov. (2010).
Stereoselectivity
Definition: Formation of one stereoisomer in preference to others.
Context: Broad umbrella covering enantio- and diastereoselectivity; essential metric in route design.
Example: Syn- vs anti-aldol selectivity.
Related Terms: Enantioselectivity, Diastereoselectivity.
Reference: IUPAC Gold Book.
Stereospecificity
Definition: Different stereoisomeric reactants give different stereoisomeric products.
Context: Defines mechanistic pathways (e.g., SN2 inversion).
Example: Walden inversion in SN2 reactions.
Related Terms: Stereoselectivity, Enantiospecificity.
Reference: IUPAC Gold Book.
Substituent
Definition: An atom or group of atoms attached to a parent chain or ring, replacing a hydrogen atom.
Context: Determines molecular properties, reactivity, and stereochemical effects.
Example: Methyl, nitro, and hydroxyl groups are common substituents.
Related Terms: Functional Group; Geminal; Vicinal.
Reference: IUPAC Gold Book (2019).
Syn (Stereochemical Descriptor)
Definition: Describes substituents on the same side in Newman or Fischer projections, often denoting syn-addition or syn-elimination.
Context: Indicates relative orientation of substituents during reactions.
Example: Syn-addition in catalytic hydrogenation.
Related Terms: Anti; Synclinal; Stereochemistry.
Reference: IUPAC Gold Book (2019).
Synclinal
Definition: Conformation where substituents on adjacent atoms have a dihedral angle of 0°-90° (commonly ~60°).
Context: Equivalent to gauche arrangement; denotes closeness in space.
Example: Synclinal butane conformation (~60° torsion angle).
Related Terms: Antiperiplanar; Gauche; Conformer.
Reference: Eliel & Wilen (1994).
Threo-
Definition: A relative stereochemical descriptor for diastereomers with two adjacent chiral centers having substituents on opposite sides in a Fischer projection.
Context: The opposite of erythro-; used in carbohydrate and amino acid stereochemistry.
Example: Threo-2,3-butanediol has hydroxyl groups on opposite sides.
Related Terms: Erythro-; Diastereomer; Relative Configuration.
Reference: Eliel & Wilen (1994).
Topicity
Definition: Relationship of identical groups/sites: homotopic, enantiotopic, diastereotopic.
Context: Guides selectivity predictions in synthesis and NMR.
Example: Diastereotopic methylene hydrogens in chiral environments.
Related Terms: Enantiotopic, Diastereotopic.
Reference: Eliel & Wilen (1994).
Topological Chirality
Definition: Chirality arising from molecular topology (e.g., knots, catenanes) rather than stereocenters.
Context: Inspires novel drug-like architectures and materials.
Example: Molecular trefoil knots.
Related Terms: Axial Chirality, Helicity.
Reference: IUPAC Gold Book.
Twist-Boat Conformation
Definition: A less strained intermediate form of cyclohexane between the boat and chair conformations.
Context: Has lower energy than pure boat form; relevant in conformational equilibria.
Example: Cyclohexane adopts twist-boat at high energy transition states.
Related Terms: Boat Conformation; Chair Conformation; Conformational Isomer.
Reference: Eliel & Wilen (1994).
Vibrational Circular Dichroism (VCD)
Definition: CD measured in the IR region arising from vibrational transitions.
Context: Determines absolute configuration without heavy atoms; valuable for pharmaceuticals.
Example: VCD assignment of chiral alcohols.
Related Terms: ROA, ECD.
Reference: Nafie, Vibrational Optical Activity (2011).
Viedma Ripening
Definition: Attrition-enhanced deracemization of conglomerates by grinding and dissolution–recrystallization.
Context: Scalable route to single enantiomers from racemates.
Example: Deracemization of amino acid derivatives.
Related Terms: Conglomerate, Deracemization.
Reference: Viedma, Phys. Rev. Lett. (2005).
Walden Inversion
Definition: Inversion of configuration at a stereocenter during SN2 displacement.
Context: Mechanistic hallmark for backside attack; used in route design.
Example: Inversion at chiral bromide with CN-.
Related Terms: SN2, Stereospecificity.
Reference: Morrison & Boyd.
Wedged (Wedge-Dash Representation)
Definition: A solid wedge bond indicates a bond projecting out of the plane toward the observer.
Context: Used in structural depictions to convey stereochemistry.
Example: Wedged bond showing front substituent in tetrahedral carbon center.
Related Terms: Hashed; Fischer Projection; Newman Projection.
Reference: Morrison & Boyd (1992).
X-ray Anomalous Dispersion
Definition: Use of wavelength-dependent scattering to distinguish enantiomers crystallographically.
Context: Determines absolute configuration via resonant scattering effects.
Example: Mo Kα vs Cu Kα anomalous signal.
Related Terms: Flack Parameter, Absolute Configuration.
Reference: Glusker et al., Crystal Structure Analysis (1994).
Z-(Zusammen)
Definition: A geometric descriptor indicating that the higher-priority substituents on a double bond are on the same side.
Context: Used to differentiate stereoisomeric alkenes and similar compounds; "Z" is the counterpart to "E".
Example: Z-2-butene has both methyl groups on the same side of the C=C bond.
Related Terms: E-; Geometric Isomerism; CIP Rules.
Reference: Cahn, Ingold & Prelog (1966).
Zig-Zag Representation
Definition: A skeletal line drawing convention where carbon-carbon bonds are drawn in a zig-zag pattern, implicitly showing sp3 geometry.
Context: Simplifies organic structure representation and emphasizes chain conformation.
Example: n-Hexane drawn as a zig-zag carbon backbone.
Related Terms: Fischer Projection; Newman Projection; Sawhorse Projection.
Reference: Clayden et al., Organic Chemistry (2012).
Zimmerman–Traxler Model
Definition: Chair-like transition state model for aldol reactions linking geometry to syn/anti outcome.
Context: Guides stereochemical planning in polyketide synthesis.
Example: Evans oxazolidinone-controlled aldol.
Related Terms: Aldol Reaction, Chiral Auxiliary.
Reference: Zimmerman & Traxler, JACS (1957).