定义Definition
手性拆分是把外消旋体（等量对映体混合物）分离成两个纯对映体的过程。由于对映体的物理性质相同，必须引入另一种手性因素（手性试剂、手性固定相、酶或手性晶种）。
Chiral resolution separates a racemate (equal mixture of enantiomers) into its pure enantiomers. Because enantiomers share physical properties, another chiral influence — a resolving agent, chiral stationary phase, enzyme or chiral seed — is needed.
主要方法Main methods
①非对映异构盐结晶：外消旋酸与手性碱（如马钱子碱、(R)-1-苯乙胺）成盐，两种非对映盐溶解度不同，分步结晶后再酸化释放；②手性色谱（手性 HPLC、SFC，多糖类固定相）；③动力学拆分：酶（脂肪酶）或手性催化剂使一个对映体反应更快；④优先结晶：外消旋混合物（聚集体）加入一种对映体晶种。
(1) Diastereomeric salt crystallisation: a racemic acid with a chiral base (brucine, (R)-1-phenylethylamine) gives diastereomeric salts of different solubility; crystallise and liberate. (2) Chiral chromatography (HPLC, SFC on polysaccharide phases). (3) Kinetic resolution with enzymes (lipases) or chiral catalysts. (4) Preferential crystallisation of conglomerates seeded with one enantiomer.
历史History
1848 年巴斯德在显微镜下用镊子手工分开外消旋酒石酸钠铵的两种镜像晶体，首次拆分了对映体；1853 年他又用奎宁等生物碱成盐拆分。
In 1848 Pasteur separated the mirror-image crystals of sodium ammonium racemate by hand under a microscope — the first resolution; in 1853 he resolved it via salts with alkaloids such as quinine.
局限与改进Limitations and improvements
经典拆分最高产率 50%，另一半需外消旋化回收；动态动力学拆分（DKR）把不需要的对映体在原位外消旋化，理论产率可达 100%。现代倾向直接用不对称合成。
Classical resolution caps yield at 50 % unless the unwanted enantiomer is racemised and recycled; dynamic kinetic resolution racemises it in situ for up to 100 %. Asymmetric synthesis is increasingly preferred.
年表Timeline
- 1848
巴斯德手工拆分酒石酸盐晶体
Pasteur separates tartrate crystals by hand
- 1853
巴斯德用生物碱成盐拆分
Pasteur resolves via alkaloid salts
- 1980s
多糖类手性色谱固定相商品化（冈本佳男等）
Polysaccharide chiral stationary phases commercialised (Okamoto and others)