Latrunculins

Latrunculins A and B are macrolides from the sponge Latrunculia magnified. Latrunculin A (>50 11M) binds close to the nucleotide binding site of G-actin and blocks the assembly with F-actin without promoting disassembly. 

In the synthesis of a macrolide 17A, known as latrunculin A, the intermediate 17B was assembled from components 17C, 17D, and 17E in a one-pot tandem process. By a retrosynthetic analysis, show how the synthesis could occur and identify a sequence of reactions and corresponding reagents. 

The involvement of the actin cytoskeleton in liposome endocytosis is studied by using cytochalasins, latrunculin, or toxin C2 to polymerize actin filaments. For a review on actin assembly and endocytosis, see Ref. (135). 

The marine macrolides latrunculin A and the less potent variation latrunculin B (5-25 pg/mL, 60 minutes) bind to actin and disrupt the cytoskeleton at low concentrations (90,91). Their mechanism of action includes binding to and sequestering actin monomers, resulting in filament depolymerization (89). 

Spector I, Shochet NR, Blasberger D, Kashman Y. Latrunculins—novel marine macrolides that disrupt microfilament and affect cell growth L Comparison with cytochalasin D. Cell Motil Cytoskeleton 1989 13 127-144. 

In the search for bioactive marine secondary metabolites, drugs or drug leads with new modes of action, many invertebrates with new modes of action have been explored and tested in a variety of assays. Many marine natural products were found to be cytotoxic to an assortment of tumor cells, Some parts of the marine natural products were also found to be ichthyotoxic so as to defend themselves. Two examples, out of many, are the latrunculins and sarcophine. ... 

Notable, from the ecological point of view, is the transfer of latrunculins in the food chain from the pray sponge to a predator nudibranch. ... 

Spector I, Shochet N, Kashman Y, Groweiss A, Latrunculins Novel marine toxins that disrupt microfilament organization in cultured cells, Science... 

Cross-cyclization of epoxides with homoallylic amines is an easy way to access tetrahydropyran moieties, which form the core structure of many biologically important natural products such as avermectins, aplysiatoxin, oscillatoxins, latrunculins, talaromycins, acutiphycins, and apicularens. Even though many methods are available for the synthesis of this moiety [14—24], its importance and wide applicability demands further methods. 

Several reactions of latrunculin B (204) were carried out as part of a study on structure-activity relationships but the biological activities of the products were not reported [403]. Two quite different total syntheses of latrunculin A (205) were briefly communicated [404,405] and full experimental details were reported later [406,407]. 

Epoxy-latrunculin A (478) and latrunculin M (479) were isolated from L. magnified. The structures were established by chemical and spectral methods [408]. Latrunculin A (205) was isolated from Fasciospongia rimosa collected in Okinawan waters and the absolute configuration was determined by X-ray analysis [409]. F. rimosa also contained the cytotoxic latrunculin S (480) and the structure was elucidated by NMR spectroscopy and chemical correlation with known congeners [410]. 

White and Kawasaki have employed a three-component strategy to access an advanced dienyl fragment in their total synthesis of (+)-latrunculin A 102 (Scheme... 

Scheme 12.16. Synthesis of latrunculin A using a three-component nucleophilic addition/Wittig olefination on dienyl phosphonium salt, by White and Kawasaki [49],...

Latrunculins A (272) and B (273) are two fish toxins first isolated from the Red Sea sponge Latrunculia magnifica (220,221). Two minor toxins named latrunculins C (274) and D (275) were isolated from the same sponge (222). Latrunculin A (272) was isolated from the Pacific nudibranch Chro-modoris elisabethina (223), and latrunculin B (273) was obtained from a nudibranch Glossodoris quadricolor (224) these nudibranchs are known... 

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