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Epothilones are natural products present in the myxobacterium Sorangium cellulossum strain 90. Due to their antitumoral activity, they are good candidates for the treatment of various forms of cancer, and epothilones B and D and some synthetic analogs are actually under advanced clinical trials. This review describes the synthesis of epothilones A and B and some of their analogs. synthetic methodologies reported in the literature to prepare epothilones A and B and some of their analogs. TOTAL SYNTHESIS OF EPOTHILONES The Danishefsky Group StrategiesThe first total synthesis of both epothilones A and B, including their respective deoxy precursors C and D, were carried out in the working group of S. J. Danishefsky [8-10].The main strategies used for the construction of the macrocycle include a macroaldolization reaction [9][10][11], an olefin metathesis approach [11,12], and a macrolactonization procedure [11]. Three key step reactions were employed: Suzuki-type coupling, aldol reaction and a stereoselective Noyori reduction [12] (Fig. 2). Metathesis (Approach I, Fig. 2) Initially, a strategy in which the C9-C10 bond would be formed during the macrocyclization reaction was chosen. The First Generation Ring-Closing OlefinTwo key intermediates 11 [11,12] and 18 [10,11] were synthesized as shown in scheme 1. Compound 11 was synthesized from β-benzyloxy(isobutyraldehyde) 7: a titanium cyclocondensation, followed by a reduction with lithium aluminum hydride provided glycal 8. Compound 9 was obtained by oxidative solvolytic fragmentation of a cycloproprane intermediate. After reductive deiodination of 9 and triphenylsilylation, cleavage of the pyran ring afforded dithioacetal 10. Protection of alcohol, followed by olefin formation and liberation of the aldehyde function led to intermediate 11. 50

Five new nitrogen heterocycles, mono-and disubstituted tetrazoles with potential synthetic and pharmacological interest, were synthesized from a, a-trehalose via the alkylation of commercial tetrazoles. This method appears to have broad scope with respect to the variations at positions 1 and 2 of tetrazole.

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Organic chemistryOrganic chemistry Z 0200 Synthetic Methodologies for the Preparation of Epothilones and Analogues -[56 refs.]. -(LUDUVICO, I.; LE HYARIC, M.; DE ALMEIDA, M. V.; DA SILVA, A. D.; Mini-Rev. Org. Chem. 3 (2006) 1, 49-75; Dep. Quim., ICE, UFJF, 36036 Juiz de Fora, Minas Gerais, Brazil; Eng.) -Lindner 40-241