Total synthesis of (+)-negamycin and its 5-epi-derivative

(+)-Negamycin was prepared in 13 steps in an overall yield of 31% from commercially available ethyl (R)(+)-4-chloro-3-hydroxybutanoate. The key step in the reaction sequence was a highly stereoselective asymmetric Michael addition of chiral amine (-)-21 [(1S,2R)-(-)-2-methoxybornyl-10-benzylamine] into the alpha,beta-unsaturated carbonyl moiety of key intermediate 8, thus establishing the second chiral center in (+)-negamycin. 5-epi-Negamycin was also prepared in a similar fashion. (C) 2009 Elsevier Ltd. All rights reserved.