Model Study toward Total Synthesis of Mytilipin C

• Published in: Bulletin of the Chemical Society of Japan Vol. 95; no. 10; pp. 1491 - 1500
• Main Authors: Umezawa, Taiki, Prakoso, Nurcahyo Iman, Tsuji, Koichi, Ogura, Yosuke, Sato, Takumi, Matsuda, Fuyuhiko
• Format: Journal Article
• Language: English
• Published: TOKYO The Chemical Society of Japan 2022; Chemical Soc Japan; Chemical Society of Japan
• Subjects: Chemistry; Chemistry, Multidisciplinary; Coupling (molecular); Ketones; Natural products; Physical Sciences; Reagents; Science & Technology; Substrates; Chlorosulfolipid; Weinreb amide; Turbo Grignard; ENANTIOSELECTIVE SYNTHESIS; LICL; STEREOCHEMISTRY; ABSOLUTE-CONFIGURATION; CARBON BOND; MALHAMENSILIPIN; DICHLORINATION; PROGRESS; CHLORINATION; CHLOROSULFOLIPIDS
• ISSN: 0009-2673; 1348-0634
• DOI: 10.1246/bcsj.20220196

Synthetic studies on mytilipin C, belonging to the chlorosulfolipid (CSL) family, with a model substrate are described. Although the isolation and structure determination of mytilipin C were first reported by Ciminiello and Fattorusso in 2002, the originally proposed structure possibly needs revision because the originally proposed structure of mytilipin B, a similar natural product, was revised through excellent work by Carreira. Our synthetic study includes three unique reactions: (1) preparation of a labile α,β-chlorinated Weinreb amide from an epoxide precursor, (2) nucleophilic addition of an acetylide to the resultant amide to give a labile α,β-chlorinated ketone, and (3) effective formation of a highly functionalized acetylide from the corresponding iodoalkyne by treatment with Turbo Grignard reagent. The vicinal coupling constants between α- and β-protons of syn- and anti-α,β-dichlorocarbonyl compounds show small and large values, respectively.