A new synthetic approach to (+)-hyacinthacine A1 and the first total synthesis and absolute configuration assignment of naturally occurring (+)-hyacinthacine A6

Abstract

Naturally occurring (1S,2R,3R,7aR)-1,2-dihydroxy-3- hydroxymethylpyrrolizidine [(+)-hyacinthacine A1 (1)] and (1S,2R,3R,5R,7aR)-1,2-dihydroxy-3-hydroxymethyl-5-methylpyrrolizidine [(+)-hyacinthacine A6 (2)] have been synthesized by Wittig's methodology using aldehyde 7, prepared from (2R,3S,4R,5R)-3,4-bis(benzyloxy)- 2′-O-(tert-butyldiphenylsilyl)-2,5-bis(hydroxymethyl)pyrrolidine (3, partially protected DALDP), as the homochiral starting material and the appropriated ylide to afford either the corresponding α,β-unsaturated ester 8 or ketone 9, which were submitted to internal lactamization and reductive amination, respectively, to give the corresponding intermediate pyrrolizidin-5-one 11 and the totally protected pyrrolizidine 14. Compounds 11 and 14 were easily transformed into the above hyacinthacines 1 and 2, respectively. © Wiley-VCH Verlag GmbH & Co. KGaA, 2007.