Diverse synthesis of the C ring fragment of bryostatins via Zn/Cu-promoted conjugate addition of α-hydroxy iodide with enone

• Published in: Chinese chemical letters Vol. 32; no. 1; pp. 1 - 4
• Main Authors: Chu, Zhiwen, Tong, Ruiqi, Yang, Yufan, Song, Xuanyi, Hu, Tian bao, Fan, Yu, Zhao, Chen, Gao, Lu, Song, Zhenlei
• Format: Journal Article
• Language: English
• Published: NEW YORK Elsevier B.V 01.01.2021; Elsevier; Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province,Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology,West China School of Pharmacy,Sichuan University,Chengdu 610041,China
• Subjects: 1,5-Hydroxy ketones; Bryostatins; Chemistry; Chemistry, Multidisciplinary; Enones; Physical Sciences; Science & Technology; Zn/Cu-promoted conjugate addition; α-Hydroxy iodide; Bryostatins; Zn/Cu-promoted conjugate addition; α-Hydroxy iodide; Enones; 1,5-Hydroxy ketones; alpha-Hydroxy iodide
• ISSN: 1001-8417; 1878-5964
• DOI: 10.1016/j.cclet.2020.11.039

A convergent approach to 1,5-hydroxy ketones, the general precursors for constructing the C ring of bryostatins, has been developed via a Zn/Cu-promoted conjugate addition of α-hydroxy iodides with enones. The approach not only leads to diverse synthesis of C ring analogs, but also enables a more concise synthesis of the known C ring intermediate in our total synthesis of bryostatin 8. [Display omitted] A convergent approach to 1,5-hydroxy ketones, the general precursors for constructing the C ring of bryostatins, has been developed via a Zn/Cu-promoted conjugate addition of α-hydroxy iodides with enones. The reaction leads to direct formation of the C21-C22 bond and tolerates diverse functionalities at the C17-, C18- and C24-positions. The approach also enables a more concise synthesis of the known C ring intermediate (10 longest linear steps and 14 total steps), in contrast to its previous synthesis (17 longest linear steps and 22 total steps) in our total synthesis of bryostatin 8.