An improved asymmetric synthesis of malyngamide U and its 2′-epimer

(Chemical Equation Presented) An accelerated and improved asymmetric synthesis of malyngamide U (1) and its 2′-epimer (2′-epi-1) was accomplished from readily available n-hexanal, ethanolamine and (R)-(-)-carvone. The key steps involveda Johnson-Claisen rearrangement in the synthesis of an unsaturated carboxylic acid 4 and an aldol reaction in the construction of the skeleton of 1 and 2′-epi-1. There are 13 steps in the synthesis, with a 2.7% overall yield for 1 and a 0.4% yield for 2′-epi-1.