9 ATPアーゼ活性化作用を有するペナレシジンA及びBの合成研究(口頭発表の部)

抄録

In 1991, penaresidin A (1) and B (2), the actomyosin ATPase activators, were isolated by Kobayashi et al. from the Okinawan marine sponge Penares sp., and characterized as a mixture of the corresponding tetraacetyl derivatives. Because nothing was known about the absolute configuration of penaresidins, we attempted the synthesis of the enantiomerically pure stereoisomers of 1 and 2 so as to determine the absolute configuration of the natural products. Three stereoisomers of penaresidin A, (2S,3R,4S,15R,16S)-, (2S,3R,4S,15S,16S)- and (2S,3R,4S,15R,16R)-1, were synthesized. The corresponding three tetraacetyl derivatives were all dextrorotatory. Because the mixture of tetraacetyl derivatives of the natural products was reported to be dextrorotatory, the stereochemistry of the azetidine ring portion of the natural 1 must be 2S,3R,4S. Then we carefully compared the 500MHz ^1H NMR spectrum of the natural tetraacetyl derivatives with those of the stereoisomers of 15 and concluded that penaresidin A is either (2S,3R,4S,15R,16R)-1 or its (15S,16S)-isomer. As for penaresidin B, we proposed the revised structure as 2' on the basis of a careful study of ^<13>C NMR spectrum of the acetyl derivative of the natural penaresidin B. We then synthesized (2S,3R,4S,15R)- and (2S,3R,4S,15S)-2'. However, we could not determine the absolute configuration of penaresidin B. In the course of the ^1H and ^<13>C NMR analysis of the stereoisomers of 15 and 26, we found each of them to exist as a mixture of two rotational isomers concerning the N-Ac bond. Indeed 15 gave back the starting single isomer of 1 upon hydrolysis. ^1H NMR study of 15 also supports our speculation. The present interpretation of the NMR properties of 15 is different from that proposed by Kamikawa. For the unambiguous determination of the stereochemistry of penaresidin A and B, we must await the reisolation of the pure material so that we shall be able to compare its chiroptical and biological properties with those of our synthetic samples.