First total synthesis and absolute configuration of naturally occurring (-)-hyacinthacine A(7) and its (-)-1-epi-isomer

摘要

A convergent synthesis of the naturally occurring alkaloid (-)-hyacinthacine A(7), a glycosidase inhibitor of the pyrrolizidine class, is described. The homochiral starting material was tri-orthogonally protected DMDP 10, derived from D-fructose. Key steps of the synthesis were the carbon-chain lengthening at C(5') in 10 to the alpha,beta-unsaturated pyrrolidine ketone 12 and the one-pot construction of the bicyclic pyrrolizidine system of 13 and 14. Another key step was the partial inversion of the configuration at C(1) in 13 which led, after total deprotection, not only to the naturally occurring target molecule 9 but also to its (-)-1-epi-isomer 19. (C) 2008 Elsevier Ltd. All rights reserved.