42 ネオカルジノスタチンクロモフォアおよび10員環アナログの合成研究(口頭発表の部)

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The antitumor antibiotic neocarzinostatin consists of an apoprotein and the chromophore 1. We describe herein a synthetic study of 1 and the 10-membered ring analog 2. An expeditious synthesis of trans-4,5-dihydroxy-2-cyclopenten-1-one 7, a key intermediate for the synthesis of 1 and 2, was achieved via an enzymatic desymmetrization of meso compounds 5 and 8. Construction of the 9-membered epoxydiyne core was accomplished by intramolecular cyclization of the aldehyde 12 with CeCl_3/LiHMDS. However, a conversion of the resultant diol 13 to the dienediyne 14 was unsuccessful. We then examined a dehydration of the secondary alcohol 19, which was successfully achieved using Tf_2O/Et_3N to give a 9-membered dienediyne 20. Glycosylation of 21 provided 23 in moderate yield, but subsequent coupling reaction of 24 with epoxydiyne fragment 25 did not proceed at all. Therefore, the coupling was conducted before glycosylation. The glycosylation of 29 with 22-β proceeded stereoselectively to give 30-α in good yield. Further synthetic study directing toward 1 is now in progress. An advanced 10-membered ring analog 39, which possesses an important functional groups in 1, such as an epoxide, naphthoate and N-methylfucosamine moieties, were synthesized. It was remarkable that 39 showed a very high DNA cleaving activity compared to the analogs which have no sugar moiety, and a different base sequence selectivity from 1. Synthesis and the DNA cleavage of 2 will be also described.
天然有機化合物討論会の論文
1998-08-31

42 ネオカルジノスタチンクロモフォアおよび10員環アナログの合成研究(口頭発表の部)

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