24 ヘミブレベトキシンBの全合成(口頭発表の部)

抄録

Hemibrevetoxin B (1), isolated from cultured cells of the red tide organism Gymnodinium breve by Prasad and Shimizu in 1989, has a 6,6,7,7-tetracyclic ether skeleton and contains 10 stereocenters. Much attention has been paid to the synthesis of polycyclic ethers including hemibrevetoxin B owing to their unusual structural framework, novel functionalities, and biological activities. Recently, Nicolaou and coworkers have reported the first total synthesis of hemibrevetoxin B. We have reported stereocontrolled synthesis of the 6,6,7,7-tetracyclic ether skeleton of 1 via the intramolecular allylic tin-aldehyde (and ketone) condensation. Chain elongation to the left-hand side aldehyde from this intermediate was difficult, and therefore we utilized 2 having hydroxypropyl side chain as a starting material. The total synthesis of 1 has been accomplished via the allylic tin methodology. The 6,6-ring system 11 prepared via the modified Nicolaou method was converted to 18. Cyclization of 18 with BF_3・OEt_2, proceeded quite smoothly and stereoselectively to give 19 in 94% yield. No diastereoisomers were detected in the cyclization step. The BF_3・OEt_2 mediated cyclization of 25 prepared from 19 by usual transformation provided the 6,6,7,7 system 26 as a single stereoisomer. Oxidation followed by Grignard reaction gave methyl carbinol derivative as a 1:1 mixture of diasteroisomers. After silyl protection, the desired isomer 27 was isolated by column chromatography. Diene side chain was introduced by Wittig olefination followed by elimination to give 30. Construction of the α-methylene aldehyde moiety was achieved by Mannich reaction with Eschenmoser's salt. ^1H and ^<13>C-NMR spectra of synthetic hemibrevetoxin B(1) was identical with those of natural product.