Synthesis of a Cyclic Analogue of Tuv N-Methyl Tubulysin
- 주제(키워드) antitumor agents , peptides , Diels-Alder reaction , asymmetric catalysis , medicinal chemistry , asymmetric synthesis
- 등재 SCIE, SCOPUS
- 발행기관 GEORG THIEME VERLAG KG
- 발행년도 2015
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000115631
- 본문언어 영어
- Published As http://dx.doi.org/10.1055/s-0034-1379900
초록/요약
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.
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