Synthesis of steroidal derivatives bearing a small ring using a catalytic [2+2] cycloaddition and a ring-contraction rearrangement

TETRAHEDRON

卷:71

Article

Arichi, Norihito¹  Hata, Kenji¹  Takemoto, Yoshiji¹  Yamada, Ken-ichi¹  Yamaoka, Yousuke¹  Takasu, Kiyosei¹ 

[1] Kyoto Univ, Grad Sch Pharmaceut Sci, Sakyo Ku, Kyoto 6068501, Japan

关键词: Steroids;    Cyclopropanes;    Cyclobutanes;    [2+2] Cycloaddition;    Ring contraction;   

DOI  :  10.1016/j.tet.2014.11.065

来源: Elsevier

【 摘 要 】

Fixing conformation by introducing a ring structure is a common strategy in drug development We demonstrate a synthesis that installs a small carbocyclic ring as a structurally-rigid unit in drug lead compounds. Both trans- and cis-cyclobutane rings were constructed in excellent selectivities by controlling the reaction temperature of an EtAlCl2-catalyzed [2+2] cycloaddition between a silyl enol ether and an alpha,beta-unsaturated ester. Spirocyclopropane rings were stereospecifically formed by our previously reported ring-contraction rearrangement of fused cyclobutanols. This strategy allowed stereodivergent access to a new class of steroidal derivatives bearing a small ring. (C) 2014 Elsevier Ltd. All rights reserved.

【 授权许可】

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