Kouichi Yoshioka

An efficient synthesis of a key intermediate for optically active 5,6-cis-carbapenem antibiotics

Abstract A versatile intermediate (18) for optically active 5,6- cis -carbapenem antibiotics was synthesized with a highly regioselective intramolecular aldol condensation as a key step.

Synthesis of lactivicin analogues

Abstract Aza analogues of lactivicin (1), a recently discovered novel antibiotic, were prepared by an application of our earlier convenient synthesis of 1 and its derivatives. A 1-unsubstituted pyrazolidinone derivative bearing 2-aminothiazol-4-yl-(Z)-methoxyiminoacetyl group exhibited in vitro antibacterial activity.

The serini reaction of 16,17-dihydroxysteroid monoacetates

Abstract The Serini reaction of 16α-alkyl (or phenyl)-1β,17β-dihydroxysteroid monoacetates 5 and 10 gave stereospecifically 16β-substituted steroids 6 and 111 in good yields. This rearrangement was shown to proceed through 1,2 hydride shift. It was found that under the same reaction conditions, 16α-vinyl-16β,17β-diol 17-acetate 5c rearranged into Z -16-ethylidene compound 24 via 1,4 hydride shift.

Synthesis of lactivicin and its derivatives

Lactivicin, a new type of antibiotic having β-lactam-like activity, and its derivatives were synthesized starting from 4-benzyloxycarbonylamino-3-isoxazolidinones and 2-oxoglutaric acid.

Synthesis of the steroid (±)-17α-ethynyl-17β-hydroxy-13β-allylgon-4-en-3-one

The title compound was synthesized using various methods of protecting the C-13 allyl group from reducing agents.

Synthesis of 5,6-cis-carbapenems related to C-19393 H2

The synthesis of 6,7-cis-7-(1-hydroxy-1-methylethyl)-3-oxa-1-azabicyclo[4.2.0]octan-8-ones (3a, b), key intermediates for the preparation of the 5,6-cis-carbapenem antibiotic C-19393 H2{sodium (5R, 6R)-3-[(E)-(2-acetamidoethenyl)-(R)-sulphinyl]-6-(1-hydroxy-1-methylethyl)-7-oxo-1-azabicyclo-[3.2.0]hept-2-ene-2-carboxylate}(1a) and its derivatives, was investigated. Sulphenylation of the 3-oxa-1-azabicyclo[4.2.0]octan-8-ones (2a, b), followed by the aldol reaction with acetone, gave the 7-(1-hydroxy-1-methylethyl)-7-sulphenyl derivatives (7a—e). Reductive desulphurization of compounds (7a—e) with an organotin hydride (tri-n-butyltin hydride or triphenyltin hydride) in the presence of a radical initiator gave rise to stereoselective formation of the cis-azetidinones (3a, b). A total synthesis of (±)-C-19393 H2(1a) and its derivatives having other substituents at the C (3) position, (1b—e), starting from (3a, b)via a carbene insertion reaction, is also described.