18 シガトキシンの合成戦略(口頭発表の部)

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Our concept of the total synthesis toward the marine polyether ciguatoxin is based on acetylene biscobalthexacarbonyl complex-mediated ether cyclizations. The cyclization of medium size ether rings according to Scheme 1 is recently established in our laboratory. The reaction proceeds via a biscobalthexacarbonyl complex-stabilized cationic intermediate, which subsequently undergoes endo cyclization to give syn/trans products. Medium size ether rings with 7-9 members have been synthesized along this line and thus the applicability in the ciguatoxin synthesis is given. Decomplexation of cobalt-acetylene was carried out under high pressure H_2-atmosphere in the presence of Wilkinson catalyst; more recently with tributyltin hydride or triethylsilane to provide olefin compounds. The ABC-fragment was synthesized starting with the BC-system 15, derived from α-methyl-D-glucose in several steps (Scheme 4). After a Lewis acid catalyzed glycosylation that coupled fragment 15 with the pentose derivative 16, the acetylenic intermediate 18 was obtained. Treatment with Co_2(CO)_8 lead to the precursor for a cyclization reaction that yielded the 7-membered A-ring with the adjacent side chain. In model studies focussing on the EFG-fragment the 7- and 9-membered ether rings 4, 8 and 25 were constructed using tri-O-acetyl-D-glucal as a commercially available precursor. The 6/7-ring system 4 was achieved after treating the Co-complex 2 with BF_3・OEt_2 to produce the 7-membered ring in compound 3, which was decomplexed using a Rh-catalyst (Scheme 1, 2, 3). The 6/9-ring system 8 was obtained in a similar procedure. The 6/7-ring system 25 that will lead to the EFG-fragment was obtained after acid catalyzed cyclization of Co-complex 23 and subsequent treatment with RhCl(PPh_3)_3/H_2 (100atm)(Scheme 5). The retrosynthetic study of the JKLM-fragment was also based on a Co-complex mediated cyclization to build the 7-membered K-ring. The key intermediate for this step will be accomplished with the connection of the J-ring 35 and the LM-fragment 37, derived from tri-O-acetyl-D-galactal and 5-menthyloxy-2-furanone, respectively. The various stereogenic centers were introduced by a stereoselective epoxidation followed by a regioselective epoxide opening and a heteroconjugate addition in the case of the compound 35 (Scheme 6). A stereoselective Michael addition to 5-menthyloxyfuranone provided the two methyl groups in fragment 37. Since a migration of the double bond, formed during the decomplexation process, occurred sometimes as a side reaction, a new method for the transformation of acetylene Co-complexes into olefins was developed. Treatment of the Co-complex with either nBu_3SnH or HSiEt_3 leads to cis olefins or vinyl silanes, respectively, in good yields without migration of the resulting double bond (Scheme 7).
1997-07-20

18 シガトキシンの合成戦略(口頭発表の部)

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