Divergent Total Syntheses of (−)‐Huperzine Q, (+)‐Lycopladine B, (+)‐Lycopladine C, and (−)‐4‐epi‐Lycopladine D. Issue 13 (8th June 2017)

• Record Type: Journal Article
• Authors: Hong, Benke; Hu, Dachao; Wu, Jinbao; Zhang, Jing; Li, Houhua; Pan, Yingming; Lei, Xiaoguang
• Is Part Of: Chemistry, an Asian journal. Volume 12:Issue 13(2017)
• Page Start: 1557
• Page End: 1567
• Publication Date: 2017-06-08
• Subjects: aldol reaction -- alkaloids -- metathesis -- natural products -- total synthesis; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/asia.201700364
• Languages: English
• ISSNs: 1861-4728

Abstract

Abstract: We report herein our synthetic efforts towards the divergent syntheses of (−)‐huperzine Q (1 ), (+)‐lycopladine B (2 ), (+)‐lycopladine C (3 ), and (−)‐lycopladine D (4 ). The 10‐step total synthesis of (−)‐huperzine Q (1 ) and the first total syntheses of (+)‐lycopladines B (2 ) and C (3 ) were accomplished through a series of cascade reactions. Our approach involved a Michael addition/aldol/intramolecular C‐alkylation sequence to forge the 6/9 spirocycle ring, and this was followed by an ethylene‐accelerated carbonyl–olefin metathesis to construct the common 6/5/9 ring system. Finally, late‐stage enamine bromofunctionalization enabled us to access (−)‐huperzine Q (1 ), (+)‐lycopladine B (2 ), and (+)‐lycopladine C (3 ), and a tandem C4‐epimerization/retro‐Claisen condensation furnished (−)‐4‐ epi ‐lycopladine D (63 ). Abstract : Divergent : Structurally complex lycopodium alkaloids are obtained by employing a unified synthetic strategy featuring Michael/aldol/C‐alkylation, ethylene‐accelerated carbonyl–olefin metathesis, late‐stage enamine bromofunctionalization, and C4‐epimerization/retro‐Claisen condensation.