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Convergent Total Synthesis of (+)-Cotylenin A

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Middle Molecular Strategy

Abstract

Herein, the convergent total synthesis of (+)-cotylenin A is described. A retrosynthetic analysis of cotylenin A generated three fragments—A- and C-ring fragments, and a sugar moiety fragment. The A-ring fragment was prepared via a catalytic asymmetric intramolecular cyclopropanation developed in our laboratory, while the C-ring fragment was prepared via the modified acyl radical cyclization of a known chiral compound. The two fragments were successfully assembled by the Utimoto coupling reaction, while the B-ring, a carbocyclic eight-membered ring, was efficiently constructed by palladium-mediated cyclization, which was discovered during our synthesis of taxol. All hydroxy groups in the 5-8-5 tricyclic scaffold were stereoselectively introduced. Moreover, a new modified reducing reagent, Me4NBH(O2CiPr)3, was developed during the course of this study. The sugar moiety fragment was successfully prepared for the first time via the consecutive carbon–oxygen bond-forming reactions and was terminated by an epoxide opening reaction. Finally, the first enantioselective total synthesis of cotylenin A was successfully accomplished in a highly convergent manner via glycosylation using Wan’s protocol. Moreover, this is the first report to investigate the specific rotation of cotylenin A through the total synthesis.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, Faculty of Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku-ku, Tokyo, 169-8555, Japan

    Masahiro Uwamori, Ryunosuke Osada, Ryoji Sugiyama, Kotaro Nagatani & Masahisa Nakada

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  1. Masahiro Uwamori
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  2. Ryunosuke Osada
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  3. Ryoji Sugiyama
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  4. Kotaro Nagatani
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  5. Masahisa Nakada
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Correspondence to Masahisa Nakada .

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  1. Graduate School of Science, Osaka University, Toyanaka, Osaka, Japan

    Koichi Fukase

  2. Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan

    Takayuki Doi

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Uwamori, M., Osada, R., Sugiyama, R., Nagatani, K., Nakada, M. (2021). Convergent Total Synthesis of (+)-Cotylenin A. In: Fukase, K., Doi, T. (eds) Middle Molecular Strategy. Springer, Singapore. https://doi.org/10.1007/978-981-16-2458-2_7

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