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 three-dimensional spatial arrangement of substituents around a stereogenic element, defined independently of any other stereocenter and commonly designated using the Cahn-Ingold-Prelog (CIP) system (R/S, E/Z, P/M).
Context: Absolute configuration provides the definitive stereochemical identity of a molecule. In pharmaceutical chemistry, it is a regulatory requirement to specify absolute configuration for chiral active pharmaceutical ingredients, as different configurations can lead to distinct pharmacological, toxicological, and metabolic outcomes. Absolute configuration must be established using reliable methods such as X-ray crystallography (with anomalous dispersion), vibrational circular dichroism, electronic circular dichroism with exciton analysis, or unambiguous chemical correlation.
Example: The assignment of (S)-thalidomide and (R)-thalidomide, where each enantiomer exhibits markedly different biological effects.
Related Terms: Relative Configuration; CIP Rules; Stereogenic Center; Absolute Stereochemistry; Misassignment of Configuration.
Reference: IUPAC. Compendium of Chemical Terminology (IUPAC Gold Book). 2nd Edition, 1997 (updated 2019).
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 H2 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.