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Chinese Journal of Organic Chemistry >

2020 , Vol. 40 >Issue 11: 3858 - 3865

DOI: https://doi.org/10.6023/cjoc202007021

Exploratory Studies on a New Strategy for the Asymmetric Total Synthesis of the Arrow Poison-Frog Alkaloid Batrachotoxin: Asymmetric Synthesis of a Functionalized CD Ring

  • Wang Xiaogang ,
  • Huang Peiqiang
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  • Fujian Provincial Key Laboratory of Chemical Biology, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005

Received date: 2020-07-07

  Revised date: 2020-08-02

  Online published: 2020-08-11

Supported by

Project supported by the National Key R&D Program of China (No. 2017YFA0207302), the National Natural Science Foundation of China (No. 21672176), and the Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT) of the Ministry of Education.

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Abstract

Among the more than 800 alkaloids isolated from skins of arrow poison-frog, batrachotoxin had attracted the most widespread attention of scientists from several fields, due to its potent cardio and nerve toxicities and challenging structure. A new strategy, which is different from all the previous total syntheses (one racemic and two enantioselective), is disclosed. This strategy features the formation of the CDE skeleton and then the ABCDE core of batrachotoxin by a key Diels-Alder reaction between A ring and CDE framework. Because A ring segment is a known compound, the first key of synthesis resides in the construction of the CDE framework. Thus, in addition to the new synthetic strategy, the synthesis of a functionalized CD ring system is developed. The synthesis started from the preparation of 2-allylcyclopentane-1,3-dione and its Michael addition with hex-1-en-3-one. The Hajos-Wiechert-type reaction of the adduct was investigated under optimized conditions using L-phenylalanine as an organocatalyst and D-camphorsulfonic acid (D-CSA) as an additive, the desired Robinson annulation proceeded smoothly to give the desired cyclization product in 75% yield and 81% ee. The latter was converted into a functionalized CD skeleton that bears all elements for elaborating to CDE framework in seven steps.

Key words： batrachotoxin; Hajos-Wiechert reaction; alkaloids; synthetic strategy; asymmetric synthesis; Tsuji-Trost reaction; Michael addition; ozonolysis

Cite this article

Wang Xiaogang , Huang Peiqiang . Exploratory Studies on a New Strategy for the Asymmetric Total Synthesis of the Arrow Poison-Frog Alkaloid Batrachotoxin: Asymmetric Synthesis of a Functionalized CD Ring[J]. Chinese Journal of Organic Chemistry, 2020 , 40(11) : 3858 -3865 . DOI: 10.6023/cjoc202007021

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