Synthesis and Biological Evaluation of Kendomycin and Its Analogues
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- 作者：Kyosuke Tanaka ; Hiroshi Matsuyama ; Masahito Watanabe ; Yukiko Fujimori ; Kodai Ishibashi ; Tomohiro Ozawa ; Tomoharu Sato ; Yoko Saikawa ; Masaya Nakata
- 刊名：Journal of Organic Chemistry
- 出版年：2014
- 出版时间：November 7, 2014
- 年：2014
- 卷：79
- 期：21
- 页码：9922-9947
- 全文大小：970K
- ISSN：1520-6904
文摘
Ansa compounds are gifts from microbes with intriguing molecular structures and highly potent bioactivities. One of the ansa compounds, kendomycin, has an oxa-metacyclophane skeleton with a quinone methide core and a fully substituted tetrahydropyran ring. Beyond a common synthetic strategy for construction of the ansa skeleton (i.e., elongation of an alkyl chain from an aromatic core followed by macrocyclization), we challenged a new method for construction of the ansa skeleton via simultaneous macrocyclization and benzannulation (using an intramolecular D枚tz benzannulation). Understanding the reactivity of various Fischer-type 蠅-alkynyloxy chromium carbene complexes with kendomycin analogue syntheses led to achievement of the total synthesis of kendomycin. Investigations of structure鈥揳ctivity relationships revealed the need for an ansa skeleton for antimicrobial activity. Therefore, we envisage that this intramolecular D枚tz benzannulation will enable divergent syntheses of ansa compounds which have important bioactive potential.