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A catalytic asymmetric synthesis of ethyl (2R,3S)-N-(p-toluenesulfonyl)-3-amino-4-cyclohexyl-2-hydroxybutyrate 7 in 96% ee from cheaply available cyclohexanone is described employing Sharpless asymmetric aminohydroxylation as the key step.

Efficient syntheses of statine and its analogues have been attained from aziridine diols 3 and ent- 3 , which were prepared via iodocyclization of trichloroacetimidates of chiral 3-buten-1,2-diols 1 and ent- 1 .

A catalytic asymmetric synthesis of ethyl (2R,3S)-N-(p-toluenesulfonyl)-3-amino-4-cyclohexyl-2-hydroxybutyrate 7 in 96% ee from cheaply available cyclohexanone is described employing Sharpless asymmetric aminohydroxylation as the key step.

The title compound was produced diastereoselectively in racemic and optically active forms by employing the [2+2] cycloaddition reaction of an imine with benzyloxyketene followed by acidic alcoholysis of the formed 3,4-cis-disubstituted β-lactam with isopropanol

Cyclohexylnorstatine [(2R, 3S)-3-amino-4-cyclohexyl-2-hydroxybutyric acid] (1) and allocyclohexylnorstatine [(2S, 3S)-3-amino-4-cyclohexyl-2-hydroxybutyric acid] (2), designed as key amino acids in renin inhibitors, were synthesized diastereoselectively and simply from Boc-L-phenylalaninol.

The title compound was produced diastereoselectively in racemic and optically active forms by employing the [2+2] cycloaddition reaction of an imine with benzyloxyketene followed by acidic alcoholysis of the formed 3,4-cis-disubstituted β-lactam with isopropanol

In our continuing search for low molecular weight, human renin inhibitors, a dipeptide derivative, morpholino-naphthyl-acyl-histidyl-cyclohexyl-norstatine (KRI-1314), was newly synthesized and estimated for oral effectiveness. This compound inhibited plasma renin from humans and from Japanese monkeys in vitro, with 50% inhibitory concentrations (IC50) of 4.7 x 10(-9) and 2.4 x 10(-8) mol/l, respectively. The mean blood pressure of sodium-depleted Japanese monkeys was lowered significantly after intravenous injection or oral administration of KRI-1314. The maximum reduction was attained 3 h after oral administration at a dose of 10 mg/kg. Plasma renin activity (PRA) was halved 1 h after oral administration of KRI-1314, and this inhibition persisted for more than 5 h. results suggest that KRI-1314, a potent, orally effective and long-lasting renin inhibitor, may become one of a new class of antihypertensive agent.

Cyclohexylnorstatine [(2R, 3S)-3-amino-4-cyclohexyl-2-hydroxybutyric acid] (1) and allocyclohexylnorstatine [(2S, 3S)-3-amino-4-cyclohexyl-2-hydroxybutyric acid] (2), designed as key amino acids in renin inhibitors, were synthesized diastereoselectively and simply from Boc-L-phenylalaninol.

An orally potent human renin inhibitor (1a) containing a novel amino acid, (2R,3S)-3-amino-4-cyclohexyl-2-hydroxybutyric acid named cyclohexylnorstatine, has been designed from the angiotensinogen transition-state and synthesized.