Strategies toward the Total Synthesis of Calyciphylline B-type Alkaloids: A Computational Perspective Aided by DFT Analysis

Abstract

Herein we describe synthetic efforts toward the total synthesis of calyciphylline B-type alkaloids. In the process, we disclose a detailed DFT study of equilibrium geometries and transition states that explains the stereochemical outcome during the formation of critical intermediates. X-ray crystallographic analysis reveals interesting conformational features in the naturally occurring deoxycalyciphylline B and its synthetic congeners.

Mechanistic study on silver(I)-catalyzed aminofluorination of unactivated alkenes

“…Luckily, quantum chemical calculation, particularly the density functional theory, [27,28] is well suited for the mechanistic study. [29][30][31][32][33][34] With the continuing interest in the silver-catalyzed radical reactions, [35,36] in the present work, a systematic study will be conducted on the mechanism for the Ag(I)/Selectfluorcatalyzed aminofluorination of unactivated alkenes with density functional theory, including the rate-determining step and regioselectivity. The present work aims to explore the nature of the Ag(I)-catalyzed radical reaction.…”

“…At present, owing to the lack of effective means to directly capture the Ag(II) and Ag(III) intermediates in the reaction solution, the study on the mechanism for this reaction is still a difficult problem. Luckily, quantum chemical calculation, particularly the density functional theory, is well suited for the mechanistic study . With the continuing interest in the silver‐catalyzed radical reactions, in the present work, a systematic study will be conducted on the mechanism for the Ag(I)/Selectfluor‐catalyzed aminofluorination of unactivated alkenes with density functional theory, including the rate‐determining step and regioselectivity.…”

Calyciphylline B-Type Alkaloids: Total Syntheses of (−)-Daphlongamine H and (−)-Isodaphlongamine H

“…In this respect, synthetic and computational studies by Hanessian and co-workers have provided valuable insight. 15 Their efforts culminated in an elegant total synthesis of isodaphlongamine H ( 5 ) 16 starting from three chiral building blocks. Importantly, Hanessian’s studies introduced isodaphlongamine H ( 5 ) as possibly being the “missing” diastereomeric congener of the calyciphylline B-type alkaloid quartet that has yet to be isolated from natural sources.…”

“…The structural revision of 3 as 4 via total synthesis warrants further study of the proposed biosynthetic pathway for all members of the calyciphylline B-type alkaloids. 10,15,16,20…”

Construction of the Tetracyclic Core of Calyciphylline B-Type Daphniphyllum Alkaloids

“…Compared with calyciphylline A-type alkaloids, calyciphylline B-type alkaloids have been less studied synthetically. In 2015, Hanessian and co-workers reported a remarkable total synthesis of a possible natural product congener isodaphlongamine H in 24 steps, whereas recently, Sarpong and co-workers achieved the first total synthesis of (−)-daphlongamine H in 20 steps. Meanwhile, some synthetic strategies have also been developed.…”