Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Angew Chem Int Ed Engl. 2021 Apr 19;60(17):9666-9671. doi: 10.1002/anie.202016343. Epub 2021 Mar 11.
The total synthesis of haliclonin A was accomplished. Starting from 3,5-dimethoxybenzoic acid, a functionalized cyclohexanone fused to a 17-membered ring was prepared through a Birch reduction/alkylation sequence, ring-closing metathesis, intramolecular cyclopropanation, and stereoselective 1,4-addition of an organocopper reagent to an enone moiety. Reductive C-N bond formation via an N,O-acetal forged the 3-azabicyclo[3.3.1]nonane core. The allyl alcohol moiety was constructed by a sequence involving stereoselective α-selenylation of an aldehyde via an enamine, syn-elimination of a selenoxide, and allylation of the aldehyde with an allylboronate. Formation of the 15-membered ring containing a skipped diene was achieved by ring-closing metathesis, and final transformations led to the synthesis of haliclonin A.
完成了 haliclonin A 的全合成。从 3,5-二甲氧基苯甲酸开始，通过 Birch 还原/烷基化序列、闭环复分解、分子内环丙基化以及有机铜试剂对烯酮部分的立体选择性 1,4-加成，制备了与 17 元环融合的功能化环己酮。通过 N,O-缩醛的还原 C-N 键形成了 3-氮杂双环[3.3.1]壬烷核心。通过涉及通过烯胺立体选择性α-硒化醛、硒氧化物的顺消除以及烯丙基硼酸酯与醛的烯丙基化的序列构建了烯丙醇部分。通过闭环复分解形成包含跳过二烯的 15 元环，并且最后的转化导致 haliclonin A 的合成。
