No abstract

Abstract:A cycloaddition approach to the functionalized tricyclo[9.3.1 .~~.~]~e n t a d e c e n e skeleton contained in ~axol@ is described. The cyclohexenone 13 was converted as illustrated to the nitrile-aldehyde 24 to which the diene and acetylenic side chains were attached by sequential nucleophilic additions. Removal of the trimethylsilyl protecting group and Dess-Martin oxidation afforded the triene 35. Microwave-assisted thermal cyclization stereoselectively generated the tricyclic ketone 36 whose structure was further established by conversion to the aromatic system 37 upon treatment with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). An epoxidation sequence was developed to introduce the epimeric C 13 alcohol 47 as required for this cycloaddition strategy. Alternatively, an allylic oxidation (CrO,, 3,s-dimethylpyrazole) afforded the C13 ketone 49.Key words: ~axol@, Diels-Alder, synthesis, diterpene, alkaloid.RCsumC : On dCcrit une approche, impliquant une cycloaddition, au squelette du tricyclo[3.3.1 .~~.~]~entadCckne fonctionnalisC contenu dans le ~axol@. Tel que reprCsentC dans le diagramme 1, on transforme la cyclohexCnone 13 en nitrile-aldehyde 24 auquel on attache les chaines laterales diCnique et acCtylCnique par une sCquence d'additions nuclCophiles. Aprks enkvement du groupe protecteur trimCthylsilyle et oxydation de Dess-Martin, on a obtenu le trikne 35. Une cyclisation thermique sous l'effet de micro-ondes a fourni stCrCosClectivement la cCtone 36 dont la structure a Ct C reconfinnee par conversion en systkme aromatique 37 par traitement avec de la 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). On a dCveloppC une sCquence d'Cpoxydations (diagramme 2) qui permet d'introduire I'alcool Cpimtre en C,, (47) qui est requis par cette stratCgie de cycloaddition. D'une rnanikre alternative, une oxydation allylique (CrO,, 3,5-dimCthylpyrazole) a fourni la cCtone en C,,. 49.

The Pd(0) based synthesis of two disilyl synthons (Z-1-trimethylsilyl-6-tert-butyldiphenylsilylhex-3-ene-1,5-diyne (18) and Z-1-trimethylsilyl-6-triisopropylsilylhex-3-ene-1,5-diyne (19)) and the selective removal of the trimethylsilyl group (K2CO3, MeOH) to afford 24 and 25 is described. These building blocks are employed in the construction of the taxamycin-12 compound 38 (16,17,18-trimethyl-2-methyloxymethoxy-9-hydroxybicyclo[9.3.1]pentadec-5-ene-3,7-diyne). The final ring closure to the 12-membered ring utilizes an intramolecular Cr–Ni mediated condensation of the iodoalkyne 37 (1,3,3-trimethyl-2-(2-oxoethyl)-4-(Z-1-methyloxymethoxy-7-iodohept-4-ene-2,6-diynyl)cyclohexene). Keyword: cancer, enediynes, synthesis, Pd(0) coupling.

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ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.