Marine polypropionates

Polypropionate chains with alternating methyl and hydroxy substituents are structural elements of many natural products with a broad spectrum of biological activities (e.g. antibiotic, antitumor). The anti-anti stereotriad is symmetric but is the most elusive one. Harada and Oku described the synthesis and the chemical desymmetrization of meso-polypropionates [152]. More recently, the problem of enantiotopic group differentiation was solved by enzymatic transesterification. The synthesis of the acid moiety of the marine polypropionate dolabriferol (Figure 6.58a) and the elaboration of the C(19)-C(27) segment of the antibiotic rifamycin S (Figure 6.58b) involved desymmetrization of meso-polypropionates [153,154]. 

Tridachiahydropyrone belongs to the family of marine polypropionates [69]. Efforts towards its total synthesis have recently led to a revision of the structure with the new proposal 2-147 [70]. The construction of the highly substituted cyclohex-enone moiety 2-146 which could be incorporated into this natural product [71] has been described by Perkins and coworkers (Scheme 2.33) [70, 72]. The conjugate addition/ Dieckmann-type cydization utilizing organocopper species as Michael donors afforded the enantiopure 2-145 in 68% yield. A further methylation of the (3-ketoester moiety in 2-145 followed by an elimination led to the desired cydohex-enone 2-146. 

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. 

Davies-Coleman MT, Garson MJ. Marine polypropionates. Nat. Prod. Rep. 1998 15 477-493. 

Ziegler EE, Becker MR. Total synthesis of (—)-denticulatins A and B marine polypropionates from Siphonaria denticu-lata.J. Org. Chem. 1990 55(9) 2800-2805. 

Paterson I, Chen DYK, Acena JL, Franklin AS. Studies in marine polypropionate synthesis total synthesis of (—)-baconipyrone C. Org. Lett. 2000 2(11) 1513-1516. 

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. 

In 1997 (-)-callystatin A (Fig. 1.2.2), a potent cytotoxic polyketide, was isolated from the marine sponge Callyspongia truncata and structurally elucidated by Ko-bayashi et al. [20] shortly afterward its absolute configuration was confirmed by the same authors by total synthesis [21]. The structure of (-)-callystatin A shows a polypropionate chain and a lactone ring connected to each other by two diene systems separated by two sp carbon atoms (Fig. 1.2.2). Since this arrangement is structurally related to several antitumor antibiotics and due to the fact that only very small amounts can be isolated from natural sources, callistatin A has been... 

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. 

Vardaro, R. R., Di Marzo, V., Marin, A., and Cimino, G., a and y pyrone polypropionates from the Mediterranean ascoglossan mollusc Ercolania funerea, Tetrahedron, 48, 9561, 1992. 

Brecknell, D. D., Collett, L., Davies-Coleman, M. T., Jones, D. D., and Garson, M. J., New noncontiguous polypropionates from marine molluscs a comment on their natural product status, Tetrahedron, 56, 2497, 2000. 

Tridachiahydropyrone (9) is produced by the marine mollusc Tridachia crispata [6], These molluscs, like many from which a wide range of y-pyrone polypropion-ate natural products has been isolated, are shell-less creatures and so are vulnerable to predation. They are known to exaete chemicals as a form of defence [19], with many of the y-pyrone polypropionates isolated showing biological activities [5],... 

Synthesis of polypropionate marine natural product (+)-membrenone C and its 7-epi-isomer has been reported using a key desymmetrization technique to create five contiguous chiral centers frombicyclic precursor 36. The diol was protected using di-f-butylsilyl bis(trifluoromethanesulfonate) and further elaborated into the natural product and its epimer (eq 14). In a separate communication, Perkins et al. utilized di-f-butylsilyl bis(trifluoromethanesulfonate) for synthesis of a model system en route to the pol)q)ropionate natural products auripyrones A and... 

Marine pulmonates of the genus Siphonaria are air breathing molluscs that resemble limpets with which they co-occur in the intertidal zone. Nearly all specimens examined contained polypropionate metabolites that are believed to be employed in chemical defense against predators. Siphonaria diemenensis collected intertidally in southeastern Australia contained two antibiotics, diemenensin-A ( 2) and -B (883)... 

Spongistatins 113, also referred to as altohyrtins in the literature, are complex marine macrolides that were isolated from marine sponges (Figure 19.10) [60]. Aside from the formidable structure, interest in these compounds has been stimulated due to their potent antitumor activity. Schwenter and Vogel, who have developed a new methodology for the preparation of polypropionates based on a double [4+3] cycloaddition, saw the spongistatins as an opportunity to... 

Sato, S., Iwata, F., Mukai, T, Yamada, S Takeo, J., Abe, A., and Kawahara, H. (2009) Indoxamycins A-F. Cytotoxic tricyclic polypropionates from a marine-derived actinomycete. J. Org. Chem., 74, 5502-5509. 

Beukes, D.R. and Davies-Coleman, M.T. (1999) Novel polypropionates from ihe South African marine mollusc Siphonaria capensis. Tetrahedron, 55, 4051-4-056. 

Cutignano, A., Cimino, G Villani, G., and Fontana, A. (2009) Origin of the Cj-unit in placidenes further insights into tax divergence of polypropionates biosynthesis in marine molluscs and fungi, Fusaripyrones. Tetrahedron, 65, 8161-8164. 

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