Synthesis of Clionastatins A and B through Enhancement of Chlorination and Oxidation Levels of Testosterone. Issue 23 (9th September 2022)

• Record Type: Journal Article
• Authors: Cui, Hao; Shen, Yang; Wang, Ruifeng; Wei, Haoxiang; Lei, Xin; Chen, Yanyu; Fu, Pengfei; Wang, Haoxiang; Bi, Ruihao; Zhang, Yandong
• Is Part Of: Chinese journal of chemistry. Volume 40:Issue 23(2022)
• Page Start: 2747
• Page End: 2755
• Publication Date: 2022-09-09
• Subjects: Steroids -- Semisynthesis -- Chlorination -- Oxidation -- Photochemistry; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/cjoc.202200425
• Languages: English
• ISSNs: 1001-604X

Abstract

Comprehensive Summary: A full account of semisyntheses of polychlorinated marine steroids clionastatins A and B is described. We have developed a unique two‐stage chlorination‐oxidation strategy that enabled concise and divergent semisyntheses of clionastatins A and B in 16 steps from inexpensive testosterone. Key transformations in chlorination stage include (a) conformationally controlled, stereospecific dichlorination through an unusual β‐chloronium intermediate to install the diequatorial C1, C2‐dichloride; (b) C4‐OH directed C19–H oxygenation followed by challenging neopentyl chlorination to install the C19–Cl. The high oxidation level was constructed through (a) the desaturation at C6–C7 through one‐pot photochemical dibromination–reductive debromination; (b) regioselective anti‐Markovnikov oxidation of the C6–C7 double bond by photoredox‐metal dual catalysis to forge the B ring enone; (c) late‐stage desaturation with SeO2 to introduce C8–C9 double bond. Wharton transposition was used to forge the D‐ring enone, and thermodynamically driven epimerization secured the cis ‐fused C/D ring system. Furthermore, we also provided a 14‐step approach to clionastatin A by optimizing the construction of the D‐ring enone with a dehydration‐oxidation sequence. Abstract :