Microbial alkaloids structure

Fig.l Molecular structures of some alkaloids that have been used and reported in microbial transformations in the last few years... 

Microbial transformations of ellipticine (15) and 9-methoxyellipticine (16) were reported by Chien and Rosazza (143, 144). Of 211 cultures screened for their abilities to transform 9-methoxyellipticine (16), several, including Botrytis alii (NRRL 2502), Cunninghamella echinulata (NRRL 1386), C. echinulata (NRRL 3655), and Penicillium brevi-compactum (ATCC 10418), achieved O-demethylation of 16 in good yield (Scheme 9). P. brevi-compactum was used to prepare 9-hydroxyellipticine (22) from the methoxylated precursor, and 150 mg of product was obtained from 400 mg of starting material (37% yield). The structure of the metabolite was confirmed by direct comparison with authentic 9-hydroxyellipticine (143). O-Demethylation is a common microbial metabolic transformation with 16 and many other alkaloids (143). Meunier et al. have also demonstrated that peroxidases catalyze the O-demethylation reaction with 9-methoxyellipticine (145). 

Scheme 20. Structures of dimeric Catharanthus alkaloids and their microbial or enzymatic transformation products.

Streptomyces punipalus converted thaicarpine (94) to hemandalinol (400), whose structure was proven by synthesis by reduction (H2/Pt-HOAc or excess NaBH4) of the alkaloid hemandaline (256). It was also shown that 256 is converted to 400 by S. punipalus, and therefore inferred that 256 is an intermediate in the overall transformation of 94. Of 22 microorganisms that were screened, 5 were shown to give metabolites from thalicarpine, but only S. punipalus was investigated in detail (237). The above microbial transformations have been reviewed (258). 

The biosynthetic studies undertaken to date on microbial marine natural products well illustrate the diversity of metabolic pathways encountered in cultured marine bacteria. Examples include brominated alkaloids such as pentabromopseudiline (Structure 2.1),19 polyketide or mixed polyketide metabolites such as oncorhyncholide (Structure 2.2),20 aplasmomycin (Structure 2.3),21 and andrimid (Structure 2.4),22 or the cyclic depsipeptide salinamide A (Structure 2.5).23 As researchers continue to define more specific culture media and a wider range of marine bacteria from diverse habitats are successfully placed into culture, the true biosynthetic potential of these prolific and adaptable microorganisms can be explored. 

Among the alkaloids, the most unusual example is an acaricidal (lethal to arachnids) monot-erpene derivative, altemicidin (Structure 18.3). This novel alkaloid was purified from amarine strain of Streptomyces sioyaensis SA-1758 isolated from marine sediments collected from the northern part of Japan. It yielded potent antitumor activity in vitro against L1210 murine leukemia and IMC carcinoma cell lines, but was toxic in vivo in mice. Altemicidin is a novel sulfur- and nitrogen-containing microbial metabolite with a monoterpene carbon skeleton.12... 

The area covered by natural products chemistry is boundless as it deals with nature itself. There is literally no limit to the topics to be dealt with. This volume 29 continues the tradition of supplying us with superb review articles written by experts. The articles in this volume deal with the screening, isolation, structure, synthesis, biosynthesis, and pharmacology of plant and microbial natural products that exhibit antimitotic, cancer chemotherapeutic, enzyme inhibitory, antiinflammatory, antibiotic and molting hormone activities. The compound types also cover a huge range of natural products, i.e., polyketides, terpenoids, sugars, alkaloids, proteins, and enzymes. 

In this review, all microbial species are named as published by the authors who first described the occurrence and chemical structures of benzodiazepine alkaloids. However, according to the modem taxonomic typification by Pitt (J. I. Pitt, The Genus Penicillium and Its Teleomorphic States EupenicUlium and Talaromyces." Academic Press, London, 1974), the names of some taxa have to be changed, as noted. 

Two alkaloids have been isolated from sponges of Plakina spp. They are the plakinamines A (106) and B (107), their structures being established mainly by comparison C-nmr-spectra with those of model from ergosterol. These bases, both microbial properties, are the first be encountered in a marine organism... 

Alkaloids represent one of the largest class of natural products with over 12000 defined structures [1], They can be summarized as nitrogen containing, mostly N-heterocyclic substances whose carbon skeleton is derived from amino acids. In a broader definition this group includes proto- and pseudoalkaloids and a number of microbial metabolites that are usually classified as antibiotics. In this review a broad definition of what to consider an alkaloid was chosen, albeit the emphasis is on alkaloids sensu strictu. 

The present volume reflects these developments, and there is a growing emphasis on bioactive natural products. Articles in this volume include those on structure-activity relationships of highly sweet natural products, chemical constituents of cchinodenns, diterpenoids from Rabdosia and Eremophila sp., structural studies on saponins, marine sesquiterpene quinoncs and antimicrobial activity of amphibian venoms. The reviews on bioactive metabolites of Phomopsis, cardenolide detection by ELISA, xenocoumacins and bioactive dihydroisocoumarins, CD studies of carbohydrate-molybdate complexes, oncogene function inhibitors from microbial secondary metabolites and Gelsemium and Lupin alkaloids present frontier developments in several areas of natural product chemistry. It is hoped that the present volume, which contains articles by eminent authorities in each field, will be received with the same enthusiasm as the previous volumes of this series. 

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