A Divergent Synthetic Route to the Vallesamidine and Schizozygine Alkaloids: Total Synthesis of (+)‐Vallesamidine and (+)‐14, 15‐Dehydrostrempeliopine. (30th October 2019)

• Record Type: Journal Article
• Authors: Zhang, Xiangyu; Anderson, James C.
• Is Part Of: Angewandte Chemie. Volume 131:Number 50(2019)
• Page Start: 18208
• Page End: 18213
• Publication Date: 2019-10-30
• Subjects: Alkaloide -- Asymmetrische Synthesen -- Hydridtransfer/Cyclisierung -- Nitro-Mannich-Reaktion -- Totalsynthesen; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201910593
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: The total synthesis of representative members of the schizozygine alkaloids, (+)‐vallesamidine and (+)‐14, 15‐dehydrostrempeliopine, were completed from a late‐stage divergent intermediate. The synthesis took advantage of efficient nitro‐group reactions with the A/B/C ring skeleton constructed concisely on a gram scale through an asymmetric Michael addition, nitro‐Mannich/lactamisation, Tsuji–Trost allylation, and intramolecular C−N coupling reaction. Other key features of the synthesis are a novel [1, 4] hydride transfer/Mannich‐type cyclisation to build ring E and a diastereoselective ring‐closing metathesis reaction to construct ring D. This approach gave access to a late‐stage C14, C15 alkene divergent intermediate that could be simply transformed into (+)‐vallesamidine, (+)‐14, 15‐dehydrostrempeliopine, and potentially other schizozygine alkaloids and unnatural derivatives. Abstract : Not macht erfinderisch, besonders bei der Zielstruktursynthese. Die Totalsynthese von (+)‐Vallesamidin und (+)‐14, 15‐Dehydrostrempeliopin war aus einem gemeinsamen Zwischenprodukt möglich, das mit anderen Alkaloiden verwandt ist und die Entwicklung einer [1, 4]‐Hydridübertragung/Mannich‐Cyclisierung zum Aufbau von Ring E erfordert (siehe Schema).