C-nucleosides. Part 2. Preparation of 2-[(1R,2S,3R,4R)-2,3-dihydroxy-4-(hydroxymethyl)cyclopentyl]thiazole-4-carboxamide (‘carbocyclic’ tiazofurin) and its antipode

Abstract

Benzyl β-aminopenicillanate 1β-oxide 9c underwent N-acylation with (1R*,2S*,3R′,4R*)-2,3-dibenzoyloxy-4-(benzoyloxymethyl)cyclopentanecarbonyl chloride 11b—assembled in nine steps from trinorbornadiene—to give a mixture of the penicillins 10d and 13c, which were readily separated by chromatography. The less polar material, identified as the diastereoisomer 10d by its conversion into (1R,5R,6R,7S)-6,7-isopropylidenedioxy-3-oxabicyclo[3.2.1]octan-2-one 24, was transformed into the title compound 1b by a four-step sequence. In a similar manner, the penicillin 13c was converted into carbatiazofurin enantiomer ent-1b. Both carbatiazofurin 1b and its enantiomer displayed cytotoxicity against a breast carcinoma cell line.