Structures, Biogenesis, and Activities

Since Hirata et al. began research into daphniphyllum alkaloids in 1966, a number of new alkaloids have been discovered. As a result, the number of known daphniphyllum alkaloids has grown markedly in recent years to a present count of 118 (compounds 1-118). These alkaloids, isolated chiefly by Yamamura and Hirata et al. are classified into six different types of backbone skeletons [1-3]. These unusual ring systems have attracted great interest as challenging targets for total synthesis or biosynthetic studies. This chapter covers the reports on daphniphyllum alkaloids that have been published between 1966 and 2006. Since the structures and stereochemistry of these alkaloids are quite complex and the representation of the structure formula has not been unified, all the natural daphniphyllum alkaloids (1-118) are listed. Classification of the alkaloids basically follows that of the previous reviews [1,2], but sections on the newly found skeletons have been added. 

It was of substantial interest when Heathcock and coworkers proposed a biogenetic pathway for daphniphyllum alkaloids [4,5] and demonstrated a biomimetic total synthesis of several of them. This review describes the recent studies on alkaloids isolated from the genus Daphniphyllum, the proposed biogenetic pathway, syntheses of daphniphyllum alkaloids based on these biogenetic proposals, and their activities. 

Modem Alkaloids Stmcture, Isolation, Synthesis and Biology. Edited by E. Eattorusso and O. Taglialatela-Scafati Copyright 2008 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 978-3-527-31521-5 

Section 18.2 surveys all the daphniphyllum alkaloids isolated so far, including our recent vork, while Sections 18.3-18.5 mainly deal with biogenetic pathways, total syntheses, the biomimetic synthesis, and the activities of these compounds. 

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I 18 Daphniphy/luin alkaloids Structures, Biogenesis, and Activities 18.3... 

Because of their suitable skeletal structure trans-CHD are applicable in the synthesis of compound classes of chemical, biological, and pharmaceutical interest. Regio- and stereoselective epoxidation of either one or two double bonds of 2, for example, opens up an approach to a group of naturally occurring cyclohexane epoxides which have attracted considerable attention because of their unusual structures, biogenesis, and biological activity [15]. 

Since a knowledge of the correct tautomeric form of the pyrimidines is a requisite for understanding the mode of binding to active sites, as well as nucleic acid structure and modification, the formulae of the conventionally-named 2- and 4-hydroxypyrimidines are presented in the correct lactam, or pyrimidone, form in this chapter. Other physical properties of the pyrimidines, such as dissociation constants, protonation sites, and distribution coefficients, are presented in cases where there is a known relation to drug activity. Biogenesis and enzyme control mechanisms are discussed where they relate to an understanding of inhibitor action. 

ABSTRACT This chapter provides a comprehensive overview of the sulfur-containing natural products that are non-sulfated and have been isolated from marine organisms. The overview covers the published literature from 1985 to 1999. A total of 482 compounds and 371 references are recorded. These secondary metabolites are organized in sections according to structural classifications by sulfur functional groups and by structural families of compounds. Comments on structural characterization, biogenesis, and biological activity have also been included. 

The simple coordination chemistry characteristic of the majority of protein-metal interactions is replaced in certain cases by irreversible covalent modifications of the protein mediated by the metal ion. These modifications are essential for the function and are templated by the structure of the protein, as no other proteins are required for the reaction to occur. These self-processing reactions result in the biogenesis of redox cofactors in some enzymes (amine oxidases, galactose oxidase, cytochrome c oxidase) and activation of hydrolytic sites in others (nitrile hydratase). The active sites of all of these enzymes are bifunctional, directing not only the catalytic turnover reaction of the mature enzyme but the modification steps required for maturation. 

An interesting aspect of the elucidation of the structure and mechanisms of TPQ biogenesis and function is that for these amine oxidases certain amino acid residues have multiple roles during cofactor biogenesis and catalysis. This is clearly true for the tyrosine residue, which is converted into TPQ, It has also been demonstrated by site-directed mutagenesis that a second strictly conserved tyrosine residue, which is present in the active site is also required for TPQ biogenesis and influences catalysis. Furthermore, the bound copper serves dual functions in cofactor biosynthesis, as shown in Scheme 4 as well as during catalysis. The latter function appears to be in stabilization of transient intermediates in the oxidative half reaction. ... 

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