Citation: Baobao Yu, Zhu-Jun Yao. A gram-scale laboratory synthesis of Annonaceous acetogenin mimic AA005[J]. Chinese Chemical Letters, ;2021, 32(1): 408-412. doi: 10.1016/j.cclet.2020.06.007 shu

A gram-scale laboratory synthesis of Annonaceous acetogenin mimic AA005

Baobao Yu ,
Zhu-Jun Yao ^*,

State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China

yaoz@nju.edu.cn

Received Date: 6 May 2020
Revised Date: 22 May 2020
Accepted Date: 3 June 2020
Available Online: 5 June 2020

Figures(5)

AA005 (1), a potent anticancer mimicking molecule of natural Annonaceous acetogenin, features a central C₂-symmetric triglycol moiety and three stereogenic centers. To support ongoing animal studies, a scalable 10-step synthesis of AA005 (1) has been studied, optimized and accomplished in this work, starting from commercially available economic materials ethylene glycol and (R)-epichlorohydrin. A regio- and stereo-controlled BF₃·Et₂O-promoted epoxide opening of (R)-epichlorohydrin with ethylene glycol was investigated, optimized and successfully applied to the scalable preparation of the crucial fragment 6a with C₂-symmetry. Further successive epoxide openings elaborated both two side chains and the whole skeleton with proper nucleophiles and electrophiles. Comparison and optimization of the reaction sequences finally led to completion of a new multi-gram synthesis of AA005 (1) with satisfactory enantiomeric and diastereomeric purity.
- AA005,
- Scalable synthesis,
- Annonaceous acetogenin mimic,
- Symmetry,
- Epoxide opening
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