Recent Progress in the Chemistry of Daphniphyllum Alkaloids

Abstract

Daphniphyllum is an evergreen species known since 1826. After initial systematic investigations, more than 320 members of this family have been isolated, which comprise complex and fascinating structures. Unique azapolycyclic architectures containing one or more quaternary stereocenters render these alkaloids synthetically challenging. This review covers efforts toward the synthesis of Daphniphyllum alkaloids spanning the period from 2005 to the beginning of 2016, including reported biological activities as well as the isolation of new members of this genus.

Total Synthesis of (−)‐Daphenylline

“…Plants of the Daphniphyllum genus have been used in Chinese herbal medicine for their curative properties and they have been a rich source of bioactive natural products . More than 320 Daphniphyllum alkaloids have been isolated from this genus to date . These architecturally diverse and complex natural products (Figure ) display a remarkable range of biological activities, such as anticancer and antioxidant properties, and promotion of nerve growth factors and vasorelaxation.…”

“…For example, logeracemin A showed significant anti‐HIV activities with an EC 50 of 4.5±0.1 μ m . The structural complexity and the biological activities of the Daphniphyllum alkaloids have attracted considerable attention from the synthetic community since the 1960s ,. Biosynthetically, the majority of these natural products are believed to arise from a daphniphylline ( 1 )‐type skeleton.…”

“…In the 1980s, Heathcock and co‐workers proposed an innovative biosynthetic pathway for these alkaloids, which led to several remarkably elegant biomimetic syntheses . Since then, significant efforts toward the synthesis of the core structures of the Daphniphyllum alkaloids have been reported by over twenty groups . However, the total synthesis of other members of the Daphniphyllum family such as daphmanidin E ( 7 ), calyciphylline N ( 8 ), longeracinphyllin A ( 9 ), himalensine ( 10 ), daphnilongeranin B ( 11 ), and daphenylline ( 12 ) were only achieved recently by the groups of Carreira, Smith, Li, Zhai, and Dixon, respectively.…”

A Concise Total Synthesis of (−)‐Himalensine A

“…The genus daphniphyllum has long been used in traditional Chinese medicine and diverse biological properties have been identified from various daphniphyllum alkaloids . The congested polycyclic ring systems of these alkaloids, along with their promising bioactivities, make them highly attractive synthetic targets ,,. Since the pioneering syntheses of several daphniphyllum alkaloids by the Heathcock group, impressive total syntheses of various daphniphyllum alkaloids have been reported by the Carreira, Smith, Li, Hanessian, Fukuyama, Zhai, Dixon, and Qiu groups …”

Glaulactams A–C, daphniphyllum alkaloids from Daphniphyllum glaucescens

“…A number of novel structures from the Daphniphyllaceae family of plants were recently reported, including himalensine A, with its 13,14,22-trinorcalyciphylline A backbone 2 , himalensine B with its 22-nor-1,13-secodaphnicyclidin framework 2 , and macropodumines A–C with fused pentacyclic ring systems 3 . The complex and fascinating structures of these alkaloids render them synthetically challenging 4 . Many types of alkaloid are reported to be produced by Daphniphyllum glaucescens , including daphniglaucin C, which has a novel structure that contains hexahydroazulene and octahydroindole ring systems 5 and daphniglaucins A and B, which have unique 1-azoniatetracyclo[5.2.2.0 1,6 0.…”