Abstract
Fragmentation of methyl 3‐O‐benzyl‐6‐bromo‐2‐O‐(tert‐butyldimethylsilyl)‐6‐deoxy‐4‐O‐(4‐methoxybenzyl)‐α‐D‐mannopyranoside (2) and in situ reductive amination give (3__R__,4__S__,5__R__)‐6‐benzylamino‐4‐benzyloxy‐5‐(tert‐butyldimethylsilyloxy)‐3‐(4‐methoxybenzyloxy)hexene (3) which is converted by intramolecular aminomercuration into an epimeric mixture of the bromomercuriopiperidine derivatives 4 and 5. The minor D‐manno epimer 4 is transformed into mesylate 10 which, upon reaction with LiN~3~ in DMF, suffers a piperidine‐pyrrolidine ring contraction to give azidomethylpyrrolidine 11. Reductive acetylation by means of thioacetic acid affords the fully protected pyrrolidine aza sugar derivative 12. The major L‐gulo epimer 5 is transformed into the mesylate 15 which, again, upon reaction with LiN~3~ in DMF undergoes piperidine‐pyrrolidine ring contraction to give the 1‐azido‐3‐O‐benzyl‐2,5‐benzylimino‐6‐bromomercurio‐1,2,5,6‐tetradeoxy‐4‐O‐(4‐methoxybenzyl)‐L‐iditol (16). Eliminative dehalomercuration by means of Zn powder is accompanied by in situ reduction of the azido group to give amino alkene 17. Intramolecular aminomercuration of 17 followed by N‐acetylation yields the protected 1,2,5,6‐tetradeoxy‐2,5‐imino‐D‐glucitol derivative 20 as the major epimer. Reductive oxygenation of 20 leads to pyrrolidine 22 which is deprotected to give title compound 1. Selective cleavage of the PMB group of 22 leads to 24. Benzylation of 22 affords again 12 from which the OH group at C‐4 is liberated by selective cleavage of the PMB ether to give pyrrolidine 13. Compound 1 inhibits NAGase from bovine kidney. magnified image