ENANTIOSELECTIVE SYNTHESIS AND DETERMINATION OF THE CONFIGURATION OF STENUSINE, THE SPREADING AGENT OF THE BEETLE STENUS-COMMA

The enantioselective total synthesis of two of the four possible stere oisomers of stenusine (1), the spreading agent of the beetle Stenus co mma, is described. The silyl ether-substituted aldehyde SAMP hydrazone 2 was alkylated with (S)-1-bromo-2-methylbutane (3) yielding the hydr azone 4 in high diastereomeric purity (de >95 %). By several steps inc luding the reduction of the hydrazone functionality and the cleavage o f the N-N bond of the intermediates, 4 was converted into the BOC-prot ected amino alcohol 6. Subsequent cyclization of 6 afforded the (S,S) diastereomer of stenusine with 96.6 % de, >99.9 % ee, and in 11.3 % ov erall yield. Repetition of this synthesis using the aldehyde RAMP hydr azone (R)-2 as the starting material produced (SR)-1 with 95.0 % de, > 99 % ee, and in 8.2 % overall yield. The synthetic samples of 1 were e mployed to investigate the stereochemistry of natural stenusine by mea ns of GC analysis on both a chiral and an achiral, stationary phase. A s a result of these studies natural stenusine was found to be a mixtur e of all four stereoisomers in a ratio of (S,S)/(SR)/(RR)/(R:S) = 43:4 0:13:4.