Total Syntheses of Calyciphylline A-Type Alkaloids (−)-10-Deoxydaphnipaxianine A, (+)-Daphlongamine E and (+)-Calyciphylline R via Late-Stage Divinyl Carbinol Rearrangements

Abstract

Among the famous Daphniphyllum alkaloids family, the calyciphylline A-type subfamily has triggered particular interest from the organic synthesis community in recent years. Here, we report divergent total syntheses of three calyciphylline A-type alkaloids, namely, (−)-10-deoxydaphnipaxianine A, (+)-daphlongamine E, and (+)-calyciphylline R. Our work highlights an efficient, divergent strategy via late-stage divinyl carbinol rearrangements, including an unprecedented oxidative Nazarov electrocyclization using an unfunctionalized tertiary divinyl carbinol and an unusual allylic alcohol rearrangement. A highly efficient “donor–acceptor” platinum catalyst was used for a critical nitrile hydration step. Moreover, the power of selective amide reductions has also been showcased by novel and classic tactics.

Total Synthesis of (±)- and (−)-Daphnillonin B

“…Daphniphyllum alkaloids (>13 subfamilies, >300 members), which have complex and diverse structures and interesting biological activities, have attracted considerable attention from the chemical synthesis community . Following Heathcock’s ground-breaking work, the groups of Carreira, A. Li, Smith, Fukuyama, Hanessian, Dixon, Zhai, Qiu, Xu, Gao, Sarpong, C. Li, and Lu have accomplished the outstanding total syntheses of several Daphniphyllum alkaloids. Remarkably, most of the polycyclic Daphniphyllum alkaloids synthesized previously have a [6-7] fused carbocyclic core (highlighted in red in Figure A; see Figure S1 in the Supporting Information (SI) for details).…”

Total Synthesis of Yuzurine-type Alkaloid Daphgraciline

“…These alkaloids have attracted great interest from synthetic chemists . After Heathcock’s pioneering work, the groups led by Carreira, A. Li, Smith, Fukuyama, Hanessian, Dixon, Zhai, Qiu, Xu, Gao, Sarpong, C. Li, and Lu have completed the remarkable total syntheses of a number of Daphniphyllum alkaloids. Notably, the yuzurine-type subfamily (Figure , 1 ), one of the largest subfamilies in Daphniphyllum alkaloids, includes ∼50 members .…”

Total Synthesis and Structural Revision of the 6,11-Epoxyisodaucane Natural Sesquiterpene Using an Anionic 8π Electrocyclic Reaction

“…E lectrocyclic reactions have long been used as powerful methods for constructing the carbocyclic moieties in natural products. 1 To date, a number of natural product syntheses that use 6π electrocyclization, 2 8π electrocyclization, 3 or cationic 4π electrocyclization (e.g., Nazarov cyclization) 4 as key steps have been reported. However, anionic 8π electrocyclization chemistry for the formation of seven-membered carbocycles appears not to have been developed.…”