Synthesis of Dihydromotuporamine C via 3‐Azonia‐Cope Rearrangement of 11‐Membered Cyclic α‐Vinylamine. Issue 46 (10th December 2020)

• Record Type: Journal Article
• Authors: Song, Zijie; Meng, Shuyu; Wang, Quanrui
• Is Part Of: ChemistrySelect. Volume 5:Issue 46(2020)
• Page Start: 14661
• Page End: 14665
• Publication Date: 2020-12-10
• Subjects: 3-azonia-Cope rearrangement -- macrocycles -- natural products -- ring expansion -- total synthesis; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202004019
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: A new synthesis of dihydromotuporamine C (dhMotC), a synthetic analogue of cytotoxic marine alkaloid, has been achieved from inexpensive starting materials. The first stage was the preparation of cyclodecanone by sequential [2+2]‐cycloaddition of N ‐(1‐cycloocten‐1‐yl)pyrrolidine with methyl propiolate and electrocyclic ring‐opening, followed by basic hydrolysis. Beckmann rearrangement of cyclodecanone oxime and several step manipulations afforded the pivotal intermediate of the N ‐benzylated 11‐membered cyclic α‐vinylamine. The final synthesis of dihydromotuporamine C involved tandem nucleophilic addition with ethynyl p ‐tolyl sulfone and 3‐azonia‐Cope rearrangement to form the 15‐membered aza‐macrocycle and reductive amination to install the appended spermidine‐like moiety. Abstract : A new pathway to dihydromotuporamine C, a highly potent anticancer synthetic analogue of marine alkaloid, was established from cyclooctanone and methyl propiolate starting materials. Key reactions involve three ring enlargements: consecutive [2+2] cycloadditions and electrocyclic ring opening, Beckmann rearrangement, and 3‐azonia‐Cope rearrangement. All the reagents required for the reaction are inexpensive and readily available, making this an advantageous synthesis strategy.