Polypropionate metabolites

B. striata, its secondary metabolic pattern, consisting of a series of uncommon polypropionates, is almost identical to that of its prey [36,37], On the contrary, if the mollusc, under maintenance in an aquarium, feeds on Haminoea navicula, it discharges [5] in the form of a yellow secretion two Haminoea metabolites, the haminols (8,9), structurally related to navenone-A (I), which possess alarm pheromone properties [38] for H. navicula. Studies on a third Aglajidae mollusc [39, 40], Philinopsis speciosa, led to the characterization of a 2-alkyl-pyridine, pulo upone (10), as a minor constituent co-occurring with two polypropionates closely related to the metabolites from the pair P. depicta-B. striata. 

Pulmonates are air-breathing molluscs that do not include many families and genera [68]. Siphonaria species from many distinct geographical areas possess a series of secondary metabolites with polypropionate skeletons characterized by the presence of ketal, pyrone and furanone moieties [47]. A rigorous biosynthetic experiment [69] proved that Siphonaria denticulata is able to... 

Biogenetic considerations [71], and a correlation of all polypropionates from pulmonate molluscs led to revision of the relative stereochemistry of pectinatone (20) and nor-pectinatone (21), metabolites of the pulmonate Siphonaria pectinata [72, 73] the point had already been questioned by Oppolzer s synthesis [74] and was definitively confirmed by two independent X-ray diffraction studies [71, 75] of pectinatone (20). 

Chemical bias toward certain molecular arrangements may also determine the commonness of certain metabolites (Pietra 1995), such as the aplysinopsins (indole alkaloids of many sponges, cnidarians, and mollusks. Chart 8.2. A), bis-indole and guanidine alkaloids (Chart 8.2.A), isoprenoids (Pietra 1995, Chart 8.2.1), and polypropionates of mollusks, sponges, and fungi (Chart 8.2.FA/PO). 

In the mollusks, only marine species are known for unusual metabolites. However, while polypropionates of marine pulmonates have de novo origin (Table 9.1), the secondary metabolites isolated from opisthobranch mollusks derive mostly from dietary cyanobacteria, seaweeds, and invertebrates. 

Norte, M., Cataldo, F., and Gonzalez, A. G., Siphonarienedione and siphonarienolone, two new metabolites from Siphonaria grisea having a polypropionate skeleton, Tetrahedron Lett., 29, 2879, 1988. 

Manker, D. C., Garson, M. J., and Faulkner, D. J., De novo biosynthesis of polypropionate metabolites in the marine pulmonate Siphonaria denticulata, J. Chem. Soc. Chem. Commun., 1061, 1988. 

FIGURE 3.1 Main classes of secondary metabolites. Fatty acids and acetogenins are derived from acetyl Coenzyme A, which forms the isopentyl diphosphate that forms terpenes. The (unusual) polypropionates derive from propionyl CoA. Alkaloids are typically modified amino acids. 

Also secondary are shifts to other kinds of food, abandonment of chemical defense, and de novo synthesis. In any event, the animals almost (but not quite) always continue to specialize upon food organisms that contain such metabolites. When the animals evolve the capacity for de novo synthesis, they may produce variants of the ancestral compound, but these variants are more physiologically active than the originals. Finally, like some other opisthobranchs, they sometimes use polypropionates synthesized de novo (see below). 

The order Anaspidea (sea hares) has already been discussed in connection with the derivation of metabolites from algae and cyanobacteria upon which these animals feed. There has been some question as to how well defended they are by metabolites in the skin. Part of the answer is that defensive metabolites do occur in the integument. Dolabella auricularia contains cyclopeptides called auripyrones (Figure 3.13.12).156 Dolabrifera dolabrifera and Petalifera petalifera contain the polypropionate dolabriferol (Figure 3.13.7).157... 

Dawe, R. D. andWright, J. L. C., The major polypropionate metabolites from the sacoglossan mollusc Elysia chlorotica, Tetrahedron Lett., 27, 2559, 1986. 

The most prominent source of marine polypropionates are mollusks, in particular opisthobranchs (13). Among a variety of polypropionates, the simplest one is possibly siphonarienal (9) isolated from Siphonaria grisea, whereas such unusual pyrone-containing metabolites as siphonarin A (10) were isolated from S. zelandica. Marine polypropionates not only play defensive roles in mollusks, but also they show antimicrobial, anti vial, and cytotoxic activities. 

A chemical study of an acetone extract of the Mexican, maura (collected at Sayulita, Mexico) resulted in the isolation of two polypropionate metabolites, vallartanone A [ 15 5] and vallartanone B [156](114) which have structures quite different from other polypropionate metabolites of the genus Siphonaria. An unrelated polypropionate, maurenone [150] which was previously isolated from the Mexican 5. maura was also present along with vallartanone A and B. It appears that pulmonates of the genus Siphonaria synthesize similar metabolites derived fiom the condensation... 

In addition to siphonarin A [140], the fljian mollusk Siphonaria normalis has been reported to contain an unusual tricyclic ketal with a trioxaadamantane ring skeleton. The structure of muamvatin 2 [161] was determined by nmr spectroscopy (118). The possible roles of the polypropionate metabolites isolated from S honaria species could be associated with its trailfollowing habits along with defense against predators. 

The total synthesis of (-)-denticulatin A, a polypropionate metabolite, was accomplished in the laboratory of F.E. Ziegler. To establish the absolute stereochemistry at C12, they utilized the Enders SAMP/RAMP hydrazone alkylation. To this end, the RAMP hydrazone of 3-pentanone was successfully alkylated with 1-bromo-2-methyl-2( )-pentene. Hydrolysis of the hydrazone under standard acidic conditions led to loss of the enantiomeric purity. This problem was avoided by using cupric acetate for the cleavage. 

Snails of the genus Siphonaria live as lung-breathing mollusks in tidal zones of the oceans. They contain secondary metabolites biosynthetically formed by condensation of polypropionate units e.g.,D.A from S. den-ticulata, C23H40O5, Mr 396.57, oil, [aJu -30.7° and siphonarin A from S. zelandica and S. atra, C28H42O8, Mr 506.64, cryst., mp. 164-166 °C, [a]o +21.7°. 

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