Manoalide synthesis

Ketones can be prepared by trapping (transmetallation) the acyl palladium intermediate 402 with organometallic reagents. The allylic chloride 400 is car-bonylated to give the mixed diallylic ketone 403 in the presence of allyltri-butylstannane (401) in moderate yields[256]. Alkenyl- and arylstannanes are also used for ketone synthesis from allylic chlorides[257,258]. Total syntheses of dendrolasin (404)f258] and manoalide[259] have been carried out employing this reaction. Similarly, formation of the ketone 406 takes place with the alkylzinc reagent 405[260],... 

The application of the AE reaction to kinetic resolution of racemic allylic alcohols has been extensively used for the preparation of enantiomerically enriched alcohols and allyl epoxides. Allylic alcohol 48 was obtained via kinetic resolution of the racemic secondary alcohol and utilized in the synthesis of rhozoxin D. Epoxy alcohol 49 was obtained via kinetic resolution of the enantioenriched secondary allylic alcohol (93% ee). The product epoxy alcohol was a key intermediate in the synthesis of (-)-mitralactonine. Allylic alcohol 50 was prepared via kinetic resolution of the secondary alcohol and the product utilized in the synthesis of (+)-manoalide. The mono-tosylated 3-butene-1,2-diol is a useful C4 building block and was obtained in 45% yield and in 95% ee via kinetic resolution of the racemic starting material. 

A 1,2-metalate rearrangement of a higher order cuprate, known as a Kodenski rearrangement [64], was used as a key step in the synthesis of the marine antiinflammatory sesterterpenoid manoalide 95 (Scheme 9.20) [65]. Treatment of the alkenyl lithium 89 (prepared from the alkenylstannane 88 with s-BuLi in a diethyl ether-pentane mixture) with the homocuprate 91 (produced from iodoalkane 90) gave the iodoalkene 94 in 72% overall yield from 88. The reaction proceeds as fol-... 

Syntheses and uses of isotopically labelled compounds 3. Synthesis of carbon-14 and tritium labelled analogues of manoalide... 

An intramolecular Heck-carbonylation/cyclization of the vinyl iodide 881 provides the 5,6-dihydropyran-2-one 882 during a total synthesis of manoalide (Equation 354) <1997CC1139>. The reaction of but-3-yn-l-ol with diaryl sulfides and carbon monoxide in the presence of a palladium(O) catalyst leads to a novel thiolactonization and hence arylthiosubstituted 5,6-dihydropyran-2-one 883 (Equation 355). Similar results are obtained with diaryl diselenides (Equation 355) <1997JOC8361>. Hydrozirconation of O-protected homopropargylic alcohols followed by carbonyla-tion and quenching with iodine provides a simple route to 5,6-dihydropyran-2-ones <1998TA949>. 

Acid chlorides couple with arylstannanes to form ketones in HMPA solution in the presence of chlo-robis(triphenylphosphinebenzyl)palladium. The same methodology has been used as part of a very efficient synthesis of manoalide and its seco derivative. The coupling of aroyl chlorides with benzylzinc bromides also produces arylbenzyl ketones under palladium catalysis.The benzylzinc bromides are formed in situ. ... 

Total synthesis of manoalide, an inhibitor of phospholipase A2, is achieved by using the present methodology as the key step (Scheme 15). ... 

Izzo, 1., Avallone, E.A., Della Monica, C., Casapullo, A., Amigo, M., Bifulco, G., and De Riccardis, F. (2004) Synthesis of potentially antiinflammatory lPL576,092-contignasterol and lPL575,092-manoalide hybrids. Tetrahedron, 60, 5587-5593. 

Katsumura, S., Fujiwara, S., and Isoe, S. (1985) Total synthesis of manoalide and seco-manoalide. Tetrahedron Lett., 26, 5827-5830. 

Amoo, V.E., De Bernardo, S., and Weigele, M. (1988) Synthesis of (S)-manoalide diol and the absolute configuration of natural manoalide. Tetrahedron Lett., 29, 2401-2404. 

Bury, P., Hareau, G., Kocienski, P., and Dhanak, D. (1994) Two synthesis of manoalide via heteroatom-assisted alkyne carbomet-allation. Tetrahedron, 50,8793-8808. 

Soriente, A., De Rosa, M., Scettri, A., and Sodano, G. (1996) A new approach to pyranofuranones, advanced intermediates for the synthesis of manoalide, cacospongionolides and their analogues. Tetrahedron Lett., 37,8007—8010. 

Pommiei A. and Kodenski, P.J. (1997) Synthesis of manoalide using a 1,2-metaIlate rearrangement. Chem. Common., 1139-1140. 

De Rosa, M., Soriente, A., Sodano, G., and Scettri, A. (2000) Enantioselective synthesis of pyranofuranone moieties of manoalide and cacospongionolide B by enzymatic and chemical approach. Tetrahedron, 56, 2095-2102. 

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