Ken Osanai

Total synthesis of (+)-brefeldin C via Lewis acid mediated cyclization of an epoxy-allylsilane

Abstract An enantioselective synthesis of (+)-brefeldin C has been achieved using Lewis acid mediated cyclization of a chiral epoxy-allylsilane as a key step.

Synthesis of diaminobutane derivatives as potent Ca2+-Permeable AMPA receptor antagonists

We synthesized diaminobutane derivatives as potent Ca(2+)-permeable AMPA receptor antagonists with non-hypotensive activity. Compound 10c showed selective Ca(2+)-permeable AMPA receptor antagonist activity and neuroprotective effects in transient global ischemia models in gerbils.

Potent inhibitors of neutral endopeptidase. 2-Biphenyl- methylglutaric acid amide derivatives

Abstract A series of glutaric acid amide derivatives were synthesized and tested for NEP inhibitory activity. Compounds 14a, 14b, 16a and 22, with a biphenylmethyl group at P′1 position, showed potent inhibitory activity.

Diastereoselective palladium(0)-catalyzed reactions of lithium enolates of chiral N-acyloxazolidinones. Asymmetric synthesis of 2-substituted (E)-4-alkylidenepentanedioates

The palladium(0)-catalyzed reactions of lithium enolates 1 of N-acyloxazolidinones with 3-acetoxy-2-methylenealkanoates 2, easily prepared via DABCO-catalyzed coupling of corresponding aldehydes with acrylates, proceeded diastereoselectively and regioselectively to give chiral N-[(E)-4-alkoxycarbonyl-4-pentenoyl]oxazolidinones3, useful intermediates of metallopeptidase inhibitors.

Studies of steroids. Part CCL. Chemical conversion of corticosteroids to 3.ALPHA.,5.ALPHA.-tetrahydro derivatives. Synthesis of allotetrahydrocortisol glucuronides and allotetrahydrocortisone glucuronides.

The synthesis of the 3- and 21-glucuronides of allotetrahydrocortisol (allo-THF) and allotetrahydrocortisone (allo-THE) is described. 5 alpha-Dihydrocortisol (5) was prepared by selective hydrogenation of 21-acetoxy-3, 11 beta, 17 alpha-trihydroxy-3,5-pregnadien-20-one 3-ethyl ether (3), followed by acid hydrolysis and saponification. When 5 alpha-dihydrocortisol 21-tetrahydropyranyl ether (6) was treated with potassium tri-sec-butylborohydride in tetrahydrofuran under mild conditions, regioselective and stereoselective reduction at C-3 took place to give allo-THF 21-tetrahydropyranyl either (7). This compound was converted into the 3- and 21-monoacetates of allo-THF and allo-THE, key intermediates. Introduction of the glucuronyl residue at C-3 or C-21 was carried out by means of the Koenigs-Knorr reaction. Prior to saponification yielding the 3-glucuronides (20,23), the alkali-sensitive ketol side chain at C-17 was protected as 20-semicarbazones.

Enantioselective synthesis of a C/D-ring synthon for the preparation of vitamin D3 metabolites

The hydrindanol (2), a C/D-ring synthon of vitamin D3 metabolites, has been synthesized enantioselectively by the use of stereoselective epoxy alcohol-initiated polyalkene cyclisation as a key step.