A cyclopropanol approach to the synthesis of both enantiomers of the C13-C21 fragment of epothilones

Efficient syntheses of both enantiomers of the C13-C21 fragment of epothilone molecules have been performed by use of enantiomeric oxiranyl-substituted cyclopropylsulfonates as key intermediates. The latter were obtained by the cyclopropanation of easily available (R)-methyl 2,3-O-isopropylideneglycerate and subsequent manipulation of the functional groups. Asymmetric allylation of 1-formylcyclopropyl pivalate led to an alternative precursor of the target compounds with moderate enantioselectivity.     

Practical syntheses of the C12-C21 epothilone subunit via catalytic asymmetric reductions: Itsuno-Corey oxazaborolidine reduction and asymmetric Noyori hydrogenation

Two practical catalytic asymmetric reductions to introduce the epothilone C15 stereocenter are described (Itsuno-Corey reduction and Noyori hydrogenation).     

Chemical Biology of Epothilones

Only a few months after the disclosure of the absolute configuration of epothilones A (R=H, see picture on the right) and B (R=Me) the first total syntheses of these natural products were reported. Interest intensified with the realization of their potential as anticancer agents with a taxol-like mechanism of action. In addition to describing the most important total syntheses and biological properties of the naturally occurring epothilones A–E, this review also provides a systematic overview of numerous epothilone analogues that have been modified in the A – D regions in order to obtain information about structure–activity relationships.     

A Novel Aldol Condensation with 2-Methyl-4-pentenal and Its Application to an Improved Total Synthesis of Epothilone B

The stabilization of the transition state through a favorable interaction between the double bond of 1 and the carbonyl group of 2 appears to be responsible for the high diastereoface selectivity of the aldol reaction. This key step in the highly concise total synthesis of epothilone B is followed by a Suzuki coupling to introduce the thiazole domain, a Noyori reduction to control the stereochemistry at C3, and a final macrolactonization (see reaction scheme). X=protecting group.     

Optimization of Fermentation Medium for Epothilones Production with Sequential Statistical Approach

A sequential statistical approach was applied to optimizing the fermentation medium of epothilones(Epos) production by means of a mutant which was obtained by treating polyangium cellulosum ATCC 15384 with nitrite and ultraviolet. The effects of different carbon sources and nitrogen sources on the fermentation medium were tested, and the suitable ones were selected. Then a uniform design was employed to design the experiments. A linear model was developed for identifying the significant components in fermen...     

NEW AND CONVENIENT SYNTHESIS OF (R) AND (S) OF 2-METHYL-3-OXA-5-(TERT-BUTYLDIPHENYLSILYLOXYL) METHYLPENTANOATE AND 2-METHYL-3-OXA-5- (TERT-BUTYLDIMETHYLSILYLOXYL)METHYLPENTANOATE

Abstract

(R) and (S) of 2-Methy1-3-oxa-5-(tert-butyldiphenylsilyloxyl)methy1pentanoate (4a. 6a) and (R) and (S) of 2-methy1-3-oxa-5-(tert-butyldimethylsilyloxyl)methylpentanoate (4b, 6b) were synthesized by the reaction of the preparative compounds (2a, 2b) with (R) and (S) methy1lactate (3, 4) in the presence of a silver (1) oxide catalyst (Method B). The title compounds are useful for the synthesis of different natural products such as epothilones.     

A cyclopropanol approach to the synthesis of the C13-C21 fragment of epothilones from diethyl (S)-malate

A convenient new approach to the synthesis of the C13-C21 epothilone fragment using the cyclopropanation of the ethoxycarbonyl groups in O-THP protected diethyl (S)-malate with ethylmagnesium bromide in the presence of titanium(IV) isopropoxide followed by site-selective cyclopropane cleavage as the key steps has been performed.