N. K. Selezneva

Cautions in the synthesis of prostaglandins. C9→C15 acetate migration

In the present communication we would like to focus on some difficulty which may be encountered in the final steps of the classical prostaglandin E1 synthesis through enone I (Scheme 1) [1–5]. This approach implies a sequence of reactions, namely reduction of the keto group in enone I to hydroxy, protection of diol IV as bis-tetrahydropyranyl (THP) ether, hydrolysis of the acetate and ester groups, oxidation of the 9-hydroxy group, and removal of the THP protecting groups. The synthesis of PGE1 according to this reaction sequence was described in [6]. The necessity of careful adherence to the conditions at the step of protection of diol IV should also be noted. It is desirable to use freshly distilled anhydrous reagents and solvents and ensure fairly fast reaction completion (in ~1–2 h). In some experiments during the THP protection of diol IV, especially when the reaction was slow, partial migration of the acetyl group from C to C with formation of C-acetate VI was possible (Scheme 2). The resulting bis-THP ethers V and VI were mixtures of diastereoisomers detected as a diffuse spot by TLC. After alkaline hydrolysis, Collins oxidation, and deprotection of the hydroxy groups, that mixture was converted into a mixture of PGE1 and enone VII which cannot be separated by silica gel chromatography. When mixture V/VI was subjected in succession to alkaline and acid hydrolysis, prostaglandin F1α (VIII) was obtained with a good overall yield. Examples of 1,2 and long-range acyl group migrations, including those occurring in prostaglandins, have been well documented [7–11]. However, despite obvious structural and functional differences between PGE1 and enone VII, it is surprising that these compounds are characterized by very similar Rf values in TLC with different eluent systems and that they almost cannot be separated by chromatography using simple columns with different lengths and efficiencies. ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 1, pp. 140–142.

New disaccharide blocks for OSW-1 and its analogs

A new disaccharide block for OSW-1 natural steroidal antitumor agent was described. Regioisomeric 2- and 3-O-p-methoxybenzoyl derivatives of phenyl 1-thio-β-d-xylopyranoside and phenyl 2-O-acetyl-1-thio-β-l-arabinopyranoside derivatives blocked at positions 3 and 4 by R3Si groups were synthesized with a view to use them in the preparation of OSW-1 analogs modified at the disaccharide fragment.

Synthesis of 6-Hydroxycarvone Derivatives and Their Oxidative Decyclization with Lead Tetraacetate

Abstract6-Hydroxy derivatives of R-(−)-carvone and 7,8-epoxycarvone were synthesized and subjected to oxidative ring cleavage by the action of lead tetraacetate. These reactions followed different patterns, depending on the substrate structure.

Carvone hydrochloride in the synthesis of thiazole-containing C11–C21-block of epithilones gem-dimethylcyclopropane analogs

Starting with R-(−)-carvone hydrochloride a synthesis was developed of the key chiral block for the epothilones gem-dimethylcyclopropane analog.

Singular features of hydrolysis of partially blocked β,δ-dihydroxy enol ether from pantolactone

Enol ether from pantolactone, 5-hydroxy-4,4-dimethyl-1-methoxy-3-methoxymethyloxy-1-pentene in hydrolysis reactions catalyzed by ions H+ and Hg++ afforded the corresponding products of methoxymethanol elimination.

Pyrrolidine synthons for β-lactams

Fused tricyclic aziridines, methyl rel-(2R,2aR,3R,4R,4aR,4bS)- and rel-(2S,2aR,3R,4R,4aR,4bS)-4-hydroxy-2,4a-dimethoxyhexahydro-1-oxa-2b-azacyclopropa[cd]pentalene-3-carboxylates, have been synthesized as possible precursors to β-lactams. The product structure has been determined by two-dimensional NMR techniques in combination with computational methods.

Functionalized β-lactams based on ( E )-1-(furan-2-yl)- N -[(4-methoxyphenyl)methyl]methanimine and its imine–imine rearrangement initiated by potassium hydride

Functionalized β-lactams were synthesized by reaction of (E)-1-(furan-2-yl)-N-[(4-methoxyphenyl)-methyl]methanimine with ketenes generated in situ from chloro- and dichloroacetic acids and 3-(methoxyimino) butanoic acid. (E)-1-(Furan-2-yl)-N-[(4-methoxyphenyl)methyl]methanimine underwent imine–imine rearrangement by the action of potassium hydride to give thermodynamically more stable (E)-N-[(furan-2-yl)-methyl]-1-(4-methoxyphenyl)methanimine.

Reaction of (2S,3S)-2-benzyloxybutane-1,2,4-triol with N,N′-carbonyldiimidazole

Abstract(2S,3S)-2-Benzyloxybutane-1,2,4-triol reacted with N,N′-carbonyldiimidazole to give a mixture of the expected 1,2-carbonate and the corresponding bis-carbonate.

Synthesis of vespertilin conjugates with OSW-1 disaccharide blocks

The reaction of vespertilin with 2-O-acetyl-3,4-bis-O-(triethylsilyl)-α-l-arabinopyranosyl trichloroacetimidate gave the corresponding glycoside. Removal of the silyl protecting group from the latter and glycosylation of the resulting diol with trichloroacetimidate derived from D-xylose afforded 3,4-regioisomeric glycosides containing OSW-1 disaccharide blocks.

Synthesis of 2-nitrogenous derivatives of methyl (2E)-(2,3-dichloro-4-oxocyclopent-2-en-1-ylidene)acetate

Methyl (2E)-(2,3-dichloro-4-oxocyclopent-2-en-1-ylidene)acetate reacted with N-nucleophiles to give the corresponding 2-substituted derivatives via replacement of the vinylic chlorine atom according to the AdNE scheme.