Chemoenzymatic Synthesis of Cylindrocyclophanes A and F and Merocyclophanes A and D

• Published in: Angewandte Chemie International Edition Vol. 62; no. 46; pp. e202307602 - n/a
• Main Authors: Chen, Kai‐Yue, Wang, Hua‐Qi, Yuan, Ye, Mou, Shu‐Bin, Xiang, Zheng
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 13-11-2023
• Edition: International ed. in English
• Subjects: Alkylation; Alkyl–Alkyl Cross-Coupling; Chemical synthesis; Chemoenzymatic Synthesis; Cylindrocyclophanes; Friedel–Crafts Alkylation; Merocyclophanes; Natural products; Polyketides
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202307602

Incorporating enzymatic reactions into natural product synthesis can significantly improve synthetic efficiency and selectivity. In contrast to the increasing applications of biocatalytic functional‐group interconversions, the use of enzymatic C−C bond formation reactions in natural product synthesis is underexplored. Herein, we report a concise and efficient approach for the synthesis of [7.7]paracyclophane natural products, a family of polyketides with diverse biological activities. By using enzymatic Friedel–Crafts alkylation, cylindrocyclophanes A and F and merocyclophanes A and D were synthesized in six to eight steps in the longest linear sequence. This study demonstrates the power of combining enzymatic reactions with contemporary synthetic methodologies and provides opportunities for the structure–activity relationship studies of [7.7]paracyclophane natural products.
Cylindrocyclophanes A and F and merocyclophanes A and D were synthesized by a chemoenzymatic approach. The synthesis features an enzymatic Friedel–Crafts alkylation, reagent‐controlled lithiation–borylation chemistry, cobalt‐catalyzed asymmetric hydroboration, and Ni‐ or Pd‐catalyzed alkyl–alkyl cross‐coupling.