Total synthesis of the 5-epimers of naturally occurring (-)-hyacinthacine A(5) and unnatural (+)-hyacinthacine A(4)

摘要

(1R,2S,3R,5S,7aR)-1,2-Dihydroxy-3-hydroxymethyl-5-methylpyrrolizidine 10 [(+)-5-epihyacinthacine A(5)] and ( 1R, 2S, 3R, 5S, 7aS)-1,2-dihydroxy-3-hydroxymethyl-5-methylpyrrolizidine 17 [ent-5-epihyacinthacine A(4)] have been synthesized by either Horner-Wadsworth-Emmons (HWE) or Wittig methodology using aldehydes 6 and 13, prepared from (2R, 3S, 4R, 5R)-3,4-dibenzyloxyN- benzyloxycarbonyl-2 '-O-tert-butyldiphenylsilyl-2,5-bis(hydroxymethyl) pyrrolidine 5 (partially protected DALDP) and (2R, 3S, 4R, 5S)-3,4-dibenzyloxy-N-benzyloxycarbonyl-2,5-bis( hydroxymethyl)-2 '-O-pivaloylpyrrolidine 12 ( partially protected DGADP), respectively, and the appropriated ylide, followed by cyclization through an internal reductive amination process of the corresponding intermediate pyrrolidinic ketones 7 and 14 and subsequent deprotection. (c) 2007 Elsevier Ltd. All rights reserved.