Enantioselective Synthesis and Determination of the Configuration of Stenusine, the Spreading Agent of the Beetle Stenus comma

Article abstract of DOI:10.1021/jo00070a024

The enantioselective total synthesis of two of the four possible stereoisomers of stenusine (1), the spreading agent of the beetle Stenus comma, is described.The silyl ether-substituted aldehyde SAMP hydrazone 2 was alkylated with (S)-1-bromo-2-methylbutane (3) yielding the hydrazone 4 in high diastereomeric purity (de>95percent).By several steps including the reduction of the hydrazone functionality and the cleavage of the N-N bond of the intermediates, 4 was converted into the BOC-protected amino alcohol 6.Subsequent cyclization of 6 afforded the (S,S) diastereomer of stenusine with 96.6percent de, >99.9percent ee, and in 11.3percent overall yield.Repetition of this synthesis using the aldehyde RAMP hydrazone (R)-2 as the starting material produced (S,R)-1 with 95.0percent de, >99percent ee, and in 8.2percent overall yield.The synthetic samples of 1 were employed to investigate the stereochemistry of natural stenusine by means of GC analysis on both a chiral and an achiral, stationary phase.As a result of these studies natural stenusine was found to be a mixture of all four stereoisomers in a ratio of (S,S)/(S,R)/(R,R)(R,S)=43:40:13:4.