Enantioselective synthesis and determination of the configuration of stenusine, the spreading agent of the beetle Stenus comma

Abstract

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 >95 %). 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 96.6 % de, >99.9 % ee, and in 11.3 % overall yield. Repetition of this synthesis using the aldehyde RAMP hydrazone (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 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)/(SR)/(RR)/(R:S) = 43:40:13:4

Intrageneric differences in the four stereoisomers of stenusine in the rove beetle genus, Stenus (Coleoptera, Staphylinidae)

“…We used a reference (Gedig, unpublished data) that resembled the natural enantiomeric composition of S. comma, for testing its chromatographic behavior in our system. 1 It emerged as unresolved enantiomeric mixtures of the diastereomers in capillary GC with a nonchiral SE 52 phase but showed the same elution order as that achieved by Enders et al (1993) with a SE 30 phase. This meant that the first peak consisted of (2′R,3R)-and (2′S,3S)-configured stenusine; the second peak combined the (2′S,3R)-and (2′R,3S)-configurations.…”

“…2 Ia). Hence, our elution order of all four stereoisomers corresponds with that of Enders et al (1993).…”

“…The reliable assignment of the elution order in enantio-GC requires the injection of structurally well-defined references (Weinert et al 1998). Enders et al (1993) synthesized (2′S,3S)-and (2′S,3R)-stenusine with high de-values, and therefore, had suitable references for the determination of the elution order for the natural stenusine of S. comma. We used a reference (Gedig, unpublished data) that resembled the natural enantiomeric composition of S. comma, for testing its chromatographic behavior in our system.…”

“…It has two stereogenic centers with four stereoisomers: (2′R,3R)-, (2′S,3R)-, (2′S,3S)-, and (2′R,3S)-stenusine. The composition of these isomers was investigated by Enders et al (1993) on S. comma. The percentile ratio (in %) of the four isomers was determined to be 13:40:43:4.…”

Alkaloids in Animals

“…This compound has a high spreading power and can efficiently propel the beetle on water surfaces, thus providing it with an elegant escape mechanism (Schildknecht et aI., 1976). Enantioselective synthesis has shown that natural stenusine is a mixture of the four possible stereoisomers (Enders et al, 1993).…”