Natural products marine

N. Ikekawa, in H. Danielsson and. Sjovah, eds.. Steroids andBile Acids, Elsevier Science Pubhshers BV, Amsterdam, the Nethedands, 1985, pp. 199—230 C. Djerassi, in P. Krogsgaard-Larsen, S. Brogger Christensen, and H. Kofod, eds., Alfred Benpon Symposium 20 Natural Products and Drug Development, Munksgaard, Copenhagen, Denmark, 1984, pp. 164—176 N. W. Withers, in P. J. Scheuer, ed.. Marine Natural Products, Vol. V, Academic Press, Inc., New York, 1983, pp. 87—130 C. Djerassi, Pure Appl Chem. 53, 873 (1981). 

P. J. Scheuer, Chemistry of Marine Nature Products, Academic Press, New York, 1973. 

The held of marine natural products chemistry, which encompasses the study of the chemical structures and biological activities of secondary metabolites produced by marine plants, animals, and microorganisms, began in earnest in the early 1960s. " This is in stark contrast to the study of terrestrial plant natural... 

Several analyses of known marine natural products according to the phylum of the source organism have revealed the richest sources of marine secondary metabolism (Figure It is clear from the data that marine algae and... 

Figure 3 Distribution of marine natural products reported in 1997 according to the phylum of the source organism...

The underlying assumption driving marine natural products chemistry research is that secondary metabolites produced by marine plants, animals, and microorganisms will be substantially different from those found in traditional terrestrial sources simply because marine life forms are very different from terrestrial life forms and the habitats which they occupy present very different physiological and ecological challenges. The expectation is that marine organisms will utilize completely unique biosynthetic pathways or exploit unique variations on well established pathways. The marine natural products chemistry research conducted to date has provided many examples that support these expectations. 

K. L. Erickson, in Marine Natural Products, Chemical and Biological Perspectives, ed. P.J. 

After a bioactive marine natural product lead structure has been identihed,... 

Figure 11 Antiinflammatory or anti-cancer marine natural products and synthetic analogs that are in commercial use or in clinical and preclinical evaluation...

The majority of promising drug candidates emerging from marine natural products research to date are potential cancer treatments. Six anti-cancer compounds that are either marine natural products or synthetic analogs of marine natural products have made it to clinical trials. The first of these compounds to enter clinical trials was didemnin B (43), one of a family of cyclic depsipetides isolated from the Caribbean tunicate Trididemnum solidum Didemnin B was advanced to Phase II clinical trials for treatment of small cell lung cancer, myeloma, prostate cancer, and melanoma. Unfortunately, no favorable responses were found so the compound has been withdrawn. Crude extracts of another Caribbean tunicate, Ecteinascidia turbinata, showed extremely... 

Pseudopterosin A is a member of a group of marine natural products which show potent antiinflammatory properties, but which are not prostaglandin biosynthesis inhibitors. Structurally similar to phosphatidyl inositol, they may function as phospholipase inhibitors, and, as such, may be the forerunners of a new class of therapeutic agents. 

Bryostatins are another class of compounds that bind to the Cl domain and result in acute activation of PKC. However, unlike phorbol esters, these marine natural products have antitumor effects. Bryostatins are currently in phase II clinical trials and show promise as anticancer drugs, particularly when combined with other adjuvant therapy. 

The novel marine natural product laulimalide (65), a metabolite of various sponges, has received attention as a potential antitumor agent due to its taxol-like ability to stabilize microtubules. There has been considerable synthetic effort toward 65, culminating within not more than 2 years in as many as ten... 

The marine natural product dynosin A (92) is a new member of the aerugi-nosin family and a novel inhibitor of thrombin and Factor Vila. In Hanessian s total synthesis of 92 [66], both the dihydroxyoctahydroindole 88 and the A3 pyrroline moiety 91 were prepared by RCM-based routes (Scheme 17). 

Nakadomarin A ((-)-145) is a marine natural product with a unique hexa-cyclic structure (Scheme 26). Recently, the first total synthesis of its enantiomer... 

Scheme 31 Efficient RCM to A4-oxocene 167 in Crimmins total syntheses of the marine natural products laurallene (168) and prelaureatin (169) [86]...

The first examples of macrocyclization by enyne RCM were used in Shair s impressive biomimetic total synthesis of the cytotoxic marine natural product longithorone A (429) [180]. This unique compound features an unusual hep-tacyclic structure which, in addition to the stereogenic centers in rings A-E, is also chiral by atropisomerism arising from hindered rotation of quinone ring G through macrocycle F (Scheme 85). It was assumed that biosynthesis of 429 could occur via an intermolecular Diels-Alder reaction between [12]paracy-... 

Heckrodt TJ, Mulzer J (2005) Marine Natural Products from Pseudopterogorgia Elisabe-thae Structures, Biosynthesis, Pharmacology and Total Synthesis. 244 1-41 Heinmaa I, see Samoson A (2005) 246 15-31 Helm L,see Toth E (2002) 221 61-101 Helmboldt H, see Hiersemann M (2005) 243 73-136 Hemscheidt T (2000) Tropane and Related Alkaloids. 209 175-206... 

A similar method was later used by the group of Tomioka [10] for the asymmetric addition of thiazolylhthium 44 to prochiral aldimines (Scheme 10) for the preparation of (S)-Boc-Doe 46, a component of antileukemic marine natural product dolastatin 10. In this case, sparteine 1 was... 

This chapter deals with single crystal x-ray diffraction as a tool to study marine natural product structures. A brief introduction to the technique is given, and the structure determination of PbTX-1 (brevetoxin A), the most potent of the neurotoxic shellfish poisons produced by Ptychodiscus brevis in the Gulf of Mexico, is presented as an example. The absolute configuration of the brevetoxins is established via the single crystal x-ray diffraction analysis of a chiral 1,2-dioxolane derivative of PbTX-2 (brevetoxin B). 

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