A novel synthetic route towards two series of enantiomerically pure cyclic analogues of 2,3-cis- and 2,3-trans-γ-aminobutyric acid (GABA) was developed. The route is based on the elongation and stereodivergent manipulation of a readily accessible enantiomerically pure γ-substituted α-aminolactone. The five-step route towards the 2,3-cis-substituted GABA analogues was achieved via straightforward carbon chain extension of the lactone using a non-classical Wittig reaction followed by chemoselective reduction and a protecting group switch. The five-step route towards the 2,3-trans-substituted GABA analogues employed elongation of the same aminolactone using a Horner-Wadsworth-Emmons reaction and highly stereoselective intramolecular oxa-Michael addition as the key synthetic manipulations. Altogether this chemistry has allowed the stereodivergent preparation of a novel class of GABA analogues in two diastereomeric series.

提出了一条新的合成路线，该路线指向两个对映体纯的2,3-顺式和2,3-反式-γ-氨基丁酸（GABA）系列环状类似物。该途径基于易于获得的对映体纯的γ-取代的α-氨基内酯的延伸和立体发散操纵。朝向2,3-五步路径顺式-取代的GABA类似物达到通过使用一种非经典Wittig反应，接着化学选择性还原内酯的直接的碳链延长和保护基团的开关。通往2,3-反式的五步路线-取代的GABA类似物利用Horner-Wadsworth-Emmons反应和高度立体选择性的分子内氧杂-Michael加成作为关键的合成操作，延长了相同的氨基内酯。总的来说，这种化学方法允许立体发散地制备两种非对映异构体系列的新型GABA类似物。