Biosynthesis daphniphyllum alkaloid

Tetracyclization. The Heathcock group1 has described a remarkably short and efficient synthesis of the skeleton of Daphniphyllum alkaloids (2) by reaction of the dialdehyde 1 with gaseous ammonia and then dissolution in acetic acid at 70°. The yield is 77%, based on the diol precursor to 1. The azadiene a and the imine b have both been isolated and identified. The conversion of a to b is an intramolecular Diels-Alder type reaction. The tetracyclization may well be involved in the biosynthesis of alkaloids such as Daphnilactone A (3). 

Two novel alkaloids with an unprecedented fused-pentacyclic skeleton, daphmanidins C (68) and D (69), consisting of l-azabicyclo[5.2.2]undecane, hexahy-dronaphthalen-l-one, and cyclopentane rings, have been isolated from the leaves of D. tdjsmanii [79]. Daphmanidin C elevated the activity of NGF biosynthesis. New daphniphyllum alkaloids, daphmanidins E (70) and F (71), have also been isolated from the leaves of D. teijsmannii, and Daphmanidins E and F showed a moderate vasorelaxant effect on rat aorta [80]. 

Four alkaloids belong to a group of secodaphniphylline-type ones represented by secodaphniphylline (2), which is considered to be the central biosynthesis precursor to the triterpenoid alkaloids that constitute the daphniphyllum alkaloids. Of them, daphniteijsmanine (18) (Fig. 3) has been newly isolated from the species Daphniphyllum teijsmanni, and its structure also been elucidated as follows (9). 

Some of these alkaloids belong to the known skeleton, while others possess unprecedented frameworks. In addition, several state -of-the-art total syntheses through cascade reaetions were also completed. To provide an update of the previous reviews by Kobayashi [25], this chapter focuses on isolation, biosynthesis, synthesis and biological activities of Daphniphyllum alkaloids reported in the past few years (2009-2012). 

Total syntheses of Daphniphyllum alkaloids are still ongoing, and the biosynthesis of Daphniphyllum alkaloids requires thorough studies to elucidate the intermediates and the relevant enzymes. The biological activities of Daphniphyllum alkaloids should be extensively investigated. In addition, plants of the genus Daphniphyllum produce the structurally diverse and complex alkaloids, which should play an important role for the plant itself from the evolutionary perspective. Biological/ecological role of these alkaloids in the life cycle of the plant should be paid much more attentions. 

C. H. Heathcock, S. Piettre, R. B. Ruggeri, J. A. Ragan, J. C. Kath, Daphniphyllum alkaloids. 12. A proposed biosynthesis of the pentacylic skeleton, proto-Daphniphylline, The Journal of Organic Chemistry 57 (1992) 2554-2566. 

K. T. Suzuki, S. Okuda, H. Niwa, M. Toda, Y. Hirata, S. Yamamma, Biosynthesis of Daphniphyllum alkaloids. Tetrahedron Lett. 14 (1973) 799-802. 

Keywords alkaloids, Daphniphyllum biosynthesis, total synthesis, pharmaeological activities... 

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