Daphniphyllum Alkaloids: Recent Findings on Chemistry and Pharmacology

Abstract

The unique polycyclic fused ring systems of Daphniphyllum alkaloids, along with their extensive bioactivities, make this family of alkaloids especially attractive targets for total synthesis and biogenetic studies. Successive discoveries of new alkaloids with unprecedented skeletons have made a great contribution to structural diversities of alkaloids elaborated by plants of the genus Daphniphyllum. By the end of 2008, more than 200 alkaloids belonging to 14 different skeletal types have been isolated from different parts of plants of thirteen Daphniphyllum species. These alkaloids show cytotoxic, antioxidant, vasorelaxant, and antiplatelet activating factor effects. The plausible biosynthetic pathways for Daphniphyllum alkaloids have been proposed and biomimetic total syntheses of some alkaloids completed. To provide an update of the previous reviews published in 2009, new structures, synthesis, and bioactivity of Daphniphyllum alkaloids reported in recent years are presented in this article. In the meantime, an additional 54 novel alkaloids have been isolated and identified. Among them, some possess unprecedented frameworks. Several inspired organic syntheses were completed.

Divergent Total Syntheses of (−)‐Daphnilongeranin B and (−)‐Daphenylline

“…So far, over 320 Daphniphyllum alkaloids with more than 20 different structure types have been isolated from this genus (Figure ),, some of which displayed a diverse range of bioactivities, including anticancer, antioxidation, elevation of nerve growth factor, vasorelaxation, and anti‐HIV properties. Owing to their fascinating architecture and promising bioactivities,, the calyciphylline A type alkaloids are among the most studied classes in the family ,. Their biosynthesis is thought to begin with the formation of secodaphnane‐type alkaloids that undergo cyclization to form yuzurimine‐type alkaloids, from which calyciphylline A type alkaloids are produced by a unique rearrangement (Figure ) .…”

Chemical constituents from Daphniphyllum macropodum

“…Daphniphyllum is the sole genus of Daphniphyllaceae, including about 30 species of evergreen trees and shrubs distributed from India to Japan and from central China to New Guinea (Kobayashi and Kubota, 2009;Wu et al, 2013). Some species of genus Daphniphyllum are used as folk medicines in China, such as Daphniphyllum macropodum and Daphniphyllum calycinum.…”

“…The previous studies on the chemical constituents of genus Daphniphyllum resulted in the isolation of hundreds of compounds belonging to alkaloids (Morita et al, 1999;Kobayashi et al, 2002;Jossang et al, 2003;Zhan et al, 2004;Li et al, 2007b;Cao et al, 2012), glucosides (Bai and Hu, 2006;Kong et al, 2007) and flavonoids (Gamez et al, 1998;Zhang et al, 2011). The fact is widely accepted that Daphniphyllum alkaloids are the chemotaxonomic makers of genus Daphniphyllum.…”

“…Up to now, more than two hundred alkaloids belonging to 14 different skeletal types have been isolated from genus Daphniphyllum (Kobayashi and Morita, 2003;Kobayashi and Kubota, 2009;Wu et al, 2013).…”

Asymmetric total synthesis of yuzurimine-type Daphniphyllum alkaloid (+)-caldaphnidine J

“…T he plant family of genus Daphniphyllum has produced a wide range of complex caged natural products-the Daphniphyllum alkaloids [1][2][3][4] . Owing to their challenging chemical structures and interesting biological profiles (such as anticarcinogenic, neurotrophic, and anti-HIV activity) 5,6 , these alkaloids have drawn much attention from the synthetic community 1,3,4 . Depending on the taxonomy, the diversified structures of the Daphniphyllum alkaloids can be categorized into 13-35 subfamilies 1,4,7 .…”