Bugula neritina Bryostatins

Two additional members of this series have been reported recently from Bugula neritina bryostatin 14, 13, was obtained in 1.02 x 10 %... 

Sudek S, LopanikNB, Waggoner LE, Hildebrand M, Anderson C, Liu HB, Patel A, Sherman DH, Haygood MG (2007) Identification of the putative bryostatin polyketide synthase gene cluster from Candidatus endobugula sertula , the uncultivated microbial symbiont of the marine bryozoan Bugula neritina. J Nat Prod 70 67-74... 

Reeves MR Eberwein RM, Rodgers LL, Testerman RR Snader KM, Forenza S. (1991) The large-scale isolation of bryostatin 1 from Bugula neritina following current good manufacturing practices. J Nat Prod 54 1265-1270. 

Marine organisms represent a largely unexplored source of unique toxic chemicals. These toxins are produced by the organisms as defense weapons against their predators. Several potent compounds demonstrating antitumor activity in vitro and in vivo have been isolated from marine organisms, e. g., the bryostatins (from Bugula neritina), dolastin 10 (from Dolabella auricularia) and halichondrine B (from Halichondria okadat) [61]. 

Davidson, S. K. and Haygood, M. G. (1999). Identification of sibling species of the Bryozoan Bugula neritina that produce different anticancer bryostatins and harbor distinct strains of the bacterial symbiont Candidatus Endobugula sertula". Biol. Bull. 196, 273-280. 

Bryostatins are a unique family of emerging cancer chemotherapeutic candidates isolated from marine bryozoa [457], They were first discovered in the bryozoan Bugula neritina, but problems with supply of sufficient quantities of this natural product hampered the study of this interesting group of marine metabolites for many years. Although the biochemical basis for their therapeutic activity is not known, these macrolactones exhibit high affinities for PKC isoenzymes, compete for the phorbol ester binding site on PKC and stimulate kinase activity in vivo and in vitro. Bryostatin 1, Fig. (54), one member of this family, is a PKC modulator in a variety of tumor systems [458,459], Bryostatin 1 is currently in phase II... 

Kerr, R. G., Lawry, J., and Gush, K. A., In vitro biosynthetic studies of the bryostatins, anticancer agents from the marine bryozoan Bugula neritina, Tetrahedron Lett., 37, 8305, 1996. 

FIGURE 3.9 Selected metabolites from bryozoans and a brachiopod. 3.9.1 Securine A from Securiflustra securirons.209 3.9.2 Bryostatin 18 from Bugula neritina,210 3.9.3 Glycerol ethers from the brachiopod... 

Davidson, S.K., Allen, S.W., Lim, G.E., Anderson, C., and Haygood, M.G., Evidence that the bacterial symbiont Candidatus endobugula sertula plays a role in bryostatin biosynthesis in the bryozoan Bugula neritina, Abstract AMS Meeting, 2000. 

Protein kinase C (calcineurin) Bryostatin 1 (Structure 16.9) Bryozoan, Bugula neritina Anticancer20... 

Bryostatin 7 (3) was the first member of the bryostatin family that was accessible by total synthesis. Its preparation was described by Masamune et al. already briefly after its isolation from Bugula neritina [8]. Their concept was based on a combination of the four synthons 4-7 (Figure 2) The (R,R)-2,5-dimethylborolanyl triflate mediated aldol reaction of aldehyde 4 with the enolate derived from ketone 5 leads after a sequence of deprotection steps, cycliza-... 

Bugula neritina) and related organisms produce substances with antibacterial, antitumor (e.g. bryostatins, didemnin B, dolastatin, girodazol, halichondrin B), anti-inflammatory (e.g. pseudopterosin E, manoalide derivatives), antifungal, antiviral, or immuno-suppressive (e.g. microcolin A and B) activity [399,400]. These compounds and/or their synthetic derivatives may be important novel bioactive pharmaceutical substances. It is also very Hkely that some new natural marine substances or their derivatives can be used as antifouling compounds, insecticides, or fungicides. 

Bryostatins are medicinally important macrolides discovered from the cosmopohtan bryozoan Bugula neritina (2). Twenty bryostatins, which all possess a 20-membered ring, are known to date. Bryostatin 1 (33) showed good antitumor activity it selectively modulates protein kinase C (12). 

Four compounds are currently under clinical investigation for their use as anticancer agents (Fimre 1). These are ecteinascidin 743 (1), from the tunicate Ecteinascidia turbinateaplidine (dehydrodidemnin B, 2) from the ascidian Aplidium albicans dolastatin 10 (3) from the sea hare Dolabella auratium and bryostatin 1 (4) from the bryozoan Bugula neritina The marine environment has also been the source of a number of anti-inflammatory compounds such as pseudopterosin E, (5). The pseudopterosins constitute the major active components in a popular line of skin care products. ... 

Bryostatins are naturally occurring antineoplastic macro-cyclic lactones derived from the marine invertebrate Bugula neritina, different varieties being isolated from different populations of the same species. More than 13 structurally related compounds have been isolated (1,2), and there is a variety of synthetic analogues (3). The bryostatins modulate the activity of protein kinase C. 

The bryostatins have been isolated from marine materials, bryozoan Bugula neritina [4] (Fig. 2b). They are macrolides with intermediate polarities. They show significant activity against lymphocytic leukemia in vitro. 

By extraction from 1000 kg of Bugula neritina 906.5 g of lymphocytic leukemia cell line active fraction was obtained. Further purification was performed with HSCCC. Bryostatins have intermediate polarity, so that n-hexane-ethyl acetate-methanol-water (3 7 5 5,... 

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