Synlett 2015; 26(08): 1063-1068
DOI: 10.1055/s-0034-1379900
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of a Cyclic Analogue of Tuv N-Methyl Tubulysin

Authors

  • Yunjeong Park

    a   College of Pharmacy & Graduate School of Pharmaceutical Sciences, Global Top 5 Research Program, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemun-Gu, Seoul 120-750, Republic of Korea   Email: ryuj@ewha.ac.kr
  • Jae Kyun Lee

    b   Center for Neuro-Medicine, Korea Institute of Science & Technology, Hwarangro 14-gil, Seongbuk-Gu, Seoul 136-791, Republic of Korea
  • Jae-Sang Ryu*

    a   College of Pharmacy & Graduate School of Pharmaceutical Sciences, Global Top 5 Research Program, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemun-Gu, Seoul 120-750, Republic of Korea   Email: ryuj@ewha.ac.kr
Further Information

Publication History

Received: 16 January 2015

Accepted after revision: 09 February 2015

Publication Date:
09 March 2015 (online)


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Abstract

Tubulysins are the most potent antimitotic agents known so far. We are interested in the conformational effect of tubulysin and herein we report the design and synthesis of a conformationally rigid cyclic analogue of Tuv N-methyl tubulysin. A conformationally rigid tetrahydropyran moiety was incorporated into the Tuv fragment via enantioselective hetero Diels–Alder reaction to prevent the rotation of the Tuv chain. The following diastereoselective reductive amination yielded the (4-methylamino)tetrahydropyranyl Tuv fragment, which was coupled to d-Mep-l-Ile dipeptide fragment and Tup fragment sequentially.

Supporting Information