Sarkomycin A methyl esters and functionalized cyclopentane blocks for brefeldin A were synthesized starting from diastereoisomeric (1R,2S)-and (1S,2R)-2-hydroxymethyl-N-[(1R)-1-phenylethyl]cyclopent-3-ene-1-carboxamides. III, V, VIII, R = α-OH; IV, VI, VII, R = β-OH. Chiral cyclopentene blocks are key synthons for the preparation of natural cyclopentanoids and their analogs [1-3]. We previously described [4] a practical procedure for the synthesis of individual vicinally functionalized diastereoisomeric cyclopentenes I and II which were used to develop rational synthetic approaches to enantiomeric cyclosarkomycins [5]. Up to now interest in sarkomycin A [6] and brefeldin A [7] as antimicrobial, anticancer, and antiviral antibiotics remains fairly strong. Studies are performed to improve methods of their synthesis [8-12], and new aspects of their application are revealed [13].In the present work we demonstrated the possibility of using compounds I and II as chiral templates by the synthesis of enantiomeric sarkomycin A methyl esters and most important cyclic precursors of brefeldin A. The structures of the target products and the retrosynthetic sequence starting from compounds I and II are shown in Scheme 1.We initially examined functionalization of the double bond in lactone IX which was obtained by acid hydrolysis of compound I in dioxane-9 N H 2 SO 4 [4]. However, seemingly promising approaches to blocks V-VIII directly from compound IX via epoxidationreduction to X, IV, and VI, reduction with BH 3 and oxidation to XI [14], and bromohydroxylation to XII and XIII turned out to be inappropriate; all these reactions led to the formation of isomer mixtures which
Diastereoisomeric [(1R,5S)-5-{[(1R)-1-phenylethyl]aminocarbonyl}cyclopent-2-en-1-yl]methyl acetate and [(1S,5R)-5-{[(1R)-1-phenylethyl]aminocarbonyl}cyclopent-2-en-1-yl]methyl acetate reacted with m-chloroperoxybenzoic acid to give the corresponding stereoisomeric α-and β-epoxy derivatives, which were identified on the basis of their spectral parameters.In the preceding communication we described the synthesis of individual bicyclic hydroxy lactams Ia and Ib [1] from readily accessible dichlorobicyclobutanone derivative II and (+)-α-methylbenzylamine (Scheme 1). Chiral functionalized cyclopentene building blocks are increasingly used in target-oriented syntheses [2][3][4]. In the present work we examined epoxidation of compounds Ia and Ib with m-chloroperoxybenzoic acid. It is known that the synthetic potential of epoxy compounds, especially cyclic ones, is very broad (isomerization, nucleophilic cleavage, electrophile-promoted rearrangements, etc. [5-7]), so that versatile functionalization of the cyclopentene fragment in Ia and Ib becomes possible.However, epoxidation of Ia and Ib was not selective. Therefore, compounds Ia and Ib were reduced with sodium tetrahydridoborate, and alcohols IIIa and IIIb thus obtained were converted into acetates IVa and IVb that are more convenient to handle with (Scheme 2).Acetates IVa and IVb smoothly and rapidly reacted with m-chloroperoxybenzoic acid to produce two couples of stereoisomeric epoxides V/VI and VII/VIII (Scheme 3); in each couple, the more polar stereoisomer slightly prevailed (~8 : 7). Compounds V and VI, as well as VII and VIII, were characterized by anomalously strongly different R f values, and they were readily separated by column chromatography on silica gel.Although allylic BocNH and trichloroacetamide groups, as well as homoallylic hydroxy group, are known to act as cis directors in the epoxidation of cyclopentene systems with m-chloroperoxybenzoic acid [8][9][10], the corresponding effect in dihomoallylic amides IVa and IVb is insignificant. Presumably, the stereoselectivity in the epoxidation of IVa and IVb is determined not only by the effect of heteroatom but also by steric factors, which act in the opposite directions.The structures of stereoisomeric epoxy derivatives V/VI and VII/VIII were assigned on the basis of their 1 H and 13 C NMR spectra. In the 1 H NMR spectrum of cis-epoxide V, the 2-H signal (δ 3.03 ppm) is located in a weaker field (see figure) than the corresponding
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