Chemical defense of a dorid nudibranch,Glossodoris quadricolor, from the red sea

Mebs, Dietrich

doi:10.1007/bf00988300

Cited by 32 publications

(23 citation statements)

References 6 publications

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“…1) (2-6). These macrolides were later also found in taxonomically unrelated organisms from different locations, thus raising questions as to the actual producer of these intriguing secondary metabolites (7)(8)(9)(10)(11)(12). § In addition to the pronounced ichthyotoxic properties of 1-6, the latrunculins were found to be cytotoxic and antivirally active.…”

mentioning

confidence: 99%

Diverted total synthesis: Preparation of a focused library of latrunculin analogues and evaluation of their actin-binding properties

Fürstner

Kirk

Fenster

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Two largely catalysis-based and highly convergent total syntheses of latrunculin A (1) and B (2) were diverted to the preparation of a focused library of analogues of these potent actin-binding macrolides that enjoy widespread use in chemical biology. Because the chosen route allows for structural variations of all characteristic parts of the natural leads, it was possible to map the previously largely unknown structure͞activity profile of this class of bioactive natural products. This led to the discovery that the removal of the methyl branches decorating the macrocycle in 2 engenders a significant increase in potency, while streamlining the synthesis to a considerable extent. Moreover, compelling evidence is provided that the conspicuous 2-thiazolidinone ring present in all naturally occurring latrunculins may be an optimal but not an essential structural motif for actin binding because it can be replaced by an oxazolidinone moiety with only slight loss in efficacy. Likewise, the inversion of the absolute configuration of the chiral center at C.16 is well accommodated. From the purely chemical perspective, this investigation attests to the maturity of alkyne metathesis, a method that has received attention as efficient means for the formation of macrocycles only recently.alkyne metathesis ͉ natural products

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confidence: 99%

Diverted total synthesis: Preparation of a focused library of latrunculin analogues and evaluation of their actin-binding properties

Fürstner

Kirk

Fenster

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…Overviews of their phylogeny, diet, sophisticated defence strategies and the chemical structures of their feeding deterrents were provided by Faulkner and Ghiselin (1983), Mebs (1985), Cimino and Ghiselin (1999) and Wägele and Klussmann-Kolb (2004). McDonald and Nybakken (1996) compiled the available information on the diet of nudibranch species from all over the world.…”

Section: Introductionmentioning

confidence: 99%

Endobacteria in the tentacles of selected cnidarian species and in the cerata of their nudibranch predators

2011

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This is the first genetic analysis comparing cultured endobacteria discovered in the tentacles of cnidarian species (Tubularia indivisa, Tubularia larynx, Corymorpha nutans, Sagartia elegans) with those found in the cerata tips of selected nudibranch species (Berghia caerulescens, Coryphella lineata, Coryphella gracilis, Janolus cristatus, Polycera faeroensis, Polycera quadrilineata, Doto coronata, Dendronotus frondosus). Shared pathogenic activities were found among other microorganisms in the Pseudoalteromonas tetraodonis group (TTX), and the Vibrio splendidus group (haemolytic, septicaemic, necrotic activity). Specific autochthonous endobacteria of extremely low similarity to their next neighbours were detected in nudibranch cerata. These organisms are regarded as new and unknown endobacteria; among them were Pseudoalteromonas luteoviolacea (95%), Orientia tsutsugamushi (84%), Gracilimonas tropica (96%), Balneola alkaliphia (95%), Loktanella rosea (97%). SEM micrographs provide insight into endobacterial aggregates in cnidarian tentacles and nudibranch cerata. Since certain nudibranch predators prey on cnidarian species, it is assumed that cnidarian tentacle bacteria are directly transferred to nudibranch cerata. The pathogenic endobacteria may contribute to the chemical defence of both the nudibranch and cnidarian species investigated.

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“…[4] These marine natural products were originally isolated as the ichthyotoxic principles of the Red Sea sponge Negombata magnifica (formerly Latrunculia magnifica), but were later also found in a variety of taxonomically unrelated organisms from different habitats. [5][6][7][8][9][10][11][12] The most notable response of eukaryotic cells to incubation with low micromolar concentrations of 1 or 2 is the rapid and selective disassembly of existing actin filaments without damage to the microtubular system. [4,13] This striking effect can be explained by the selective formation of 1:1 complexes of latrunculin with the actin monomers (G-actin, globular actin) which thereby lose their ability to polymerize to intact protein fibers (F-actin, fibrous actin).…”

Section: Introductionmentioning

confidence: 99%

Total Syntheses of the Actin‐Binding Macrolides Latrunculin A, B, C, M, S and 16‐epi‐Latrunculin B

Fürstner

Souza

Turet

et al. 2006

Chemistry A European J

125

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The latrunculins are highly selective actin-binding marine natural products and as such play an important role as probe molecules for chemical biology. A short, concise and largely catalysis-based approach to this family of bioactive macrolides is presented. Specifically, the macrocyclic skeletons of the targets were forged by ring-closing alkyne metathesis (RCAM) or enyne–yne metathesis of suitable diyne or enyne–yne precursors, respectively. This transformation was best achieved with the aid of [(tBu)(Me₂C₆H₃)N]₃Mo (37) as precatalyst activated in situ with CH₂Cl₂, as previously described. This catalyst system is strictly chemoselective for the triple bond and does not affect the olefinic sites of the substrates. Moreover, the molybdenum-based catalyst turned out to be broader in scope than the Schrock alkylidyne complex [(tBuO)₃WCΞCMe₃] (38), which afforded cycloalkyne 35 in good yield but failed in closely related cases. The required metathesis precursors were assembled in a highly convergent fashion from three building blocks derived from acetoacetate, cysteine, and (+)-citronellene. The key fragment coupling can either be performed via a titanium aldol reaction or, preferentially, by a sequence involving a Horner–Wadsworth–Emmons olefination followed by a protonation/cyclization/diastereoselective hydration cascade. Iron-catalyzed C[BOND]C-bond formations were used to prepare the basic building blocks in an efficient manner. This synthesis blueprint gave access to latrunculin B (2), its naturally occurring 16-epimer 3, as well as the even more potent actin binder latrunculin A (1) in excellent overall yields. Because of the sensitivity of the 1,3-diene motif of the latter, however, the judicious choice of protecting groups and the proper phasing of their cleavage was decisive for the success of the total synthesis. Since latrunculin A and B had previously been converted into latrunculin S, C and M, respectively, formal total syntheses of these congeners have also been achieved. Finally, a previously unknown acid-catalyzed degradation pathway of these bioactive natural products is described. The cysteine-derived ketone 18, the tetrahydropyranyl segment 31 serving as the common synthesis platform for the preparation of all naturally occurring latrunculins, as well as the somewhat strained cycloalkyne 35 formed by the RCAM reaction en route to 2 were characterized by X-ray crystallography

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Chemical defense of a dorid nudibranch,Glossodoris quadricolor, from the red sea

Cited by 32 publications

References 6 publications

Diverted total synthesis: Preparation of a focused library of latrunculin analogues and evaluation of their actin-binding properties

Diverted total synthesis: Preparation of a focused library of latrunculin analogues and evaluation of their actin-binding properties

Endobacteria in the tentacles of selected cnidarian species and in the cerata of their nudibranch predators

Total Syntheses of the Actin‐Binding Macrolides Latrunculin A, B, C, M, S and 16‐epi‐Latrunculin B

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