Pfizer Global R&D, Sandwich, Kent CT13 9NJ, UK.
J Org Chem. 2010 Dec 3;75(23):8133-46. doi: 10.1021/jo101756g. Epub 2010 Nov 2.
Oxidation of enantiomerically pure (R)-N(1)-1'-(1''-naphthyl)ethyl-2,7-dihydro-1H-azepine with m-CPBA in the presence of HBF(4) and BnOH gave (3S,4R,5S,6S,1'R)-N(1)-1'-(1''-naphthyl)ethyl-3-hydroxy-4-benzyloxy-5,6-epoxyazepane as the major product and as a single diastereoisomer after chromatography. Elaboration of this highly functionalized intermediate via ring contraction to (2S,3R,4S,5S,1'R)-N(1)-benzyl-2-chloromethyl-3-benzyloxy-4,5-epoxypiperidine followed by regioselective epoxide ring opening, functional group manipulation, and deprotection gave (+)-1-deoxyaltronojirimycin. Alternatively, resolution of (RS,RS)-N(1)-benzyl-3-hydroxy-4-benzyloxy-2,3,4,7-tetrahydro-1H-azepine or (3RS,4SR,5RS,6RS)-N(1)-benzyl-3-hydroxy-4-benzyloxy-5,6-epoxyazepane by preparative chiral HPLC and subsequent elaboration allows access to the enantiomers of 1-deoxynojirimycin and 1-deoxyaltronojirimycin, respectively.
在 m-CPBA、HBF4 和 BnOH 的存在下，将对映纯的 (R)-N(1)-1'-(1''-萘基)乙基-2,7-二氢-1H-氮杂环庚烷氧化，得到 (3S,4R,5S,6S,1'R)-N(1)-1'-(1''-萘基)乙基-3-羟基-4-苄氧基-5,6-环氧氮杂环庚烷，这是主要产物，并且在经过色谱分离后为单一非对映异构体。通过环收缩将这个高度官能化的中间体进一步转化为 (2S,3R,4S,5S,1'R)-N(1)-苄基-2-氯甲基-3-苄氧基-4,5-环氧哌啶，然后进行区域选择性环氧化物开环、官能团操作和脱保护，得到 (+)-1-去氧阿特罗诺吉里霉素。或者，通过制备性手性 HPLC 对 (RS,RS)-N(1)-苄基-3-羟基-4-苄氧基-2,3,4,7-四氢-1H-氮杂环庚烷或 (3RS,4SR,5RS,6RS)-N(1)-苄基-3-羟基-4-苄氧基-5,6-环氧氮杂环庚烷进行拆分，然后进一步修饰，可以分别得到 1-去氧诺吉里霉素和 1-去氧阿特罗诺吉里霉素的对映异构体。
