Syntheses of the enantiomers of 1-deoxynojirimycin and 1-deoxyaltronojirimycin via chemo- and diastereoselective olefinic oxidation of unsaturated amines.
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.
Pfizer Global R&D, Sandwich, Kent CT13 9NJ, UK.
Sharan K
SK
Bagal
Stephen G
SG
Davies
James A
JA
Lee
Paul M
PM
Roberts
Philip M
PM
Scott
James E
JE
Thomson
D017485:1-Deoxynojirimycin / Q000138:chemical synthesis*; D000475:Alkenes / Q000737:chemistry*; D000588:Amines / Q000737:chemistry*; D004852:Epoxy Compounds / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013237:Stereoisomerism
D000475:Alkenes; D000588:Amines; D004852:Epoxy Compounds; D017485:1-Deoxynojirimycin