Method of forming amino acid-derived diaminopropanols useful as chemical intermediates for protease-inhibitors

A method for producing a protease inhibitor synthetic intermediate represented by the formula ##STR15## and salts thereof, wherein:

• R.sup.1 is a protecting group;
• R.sup.2 is selected from the group consisting of --H, C1-C18 alkyl, aryl, heteroaryl, acetyl and tosyl;
• R.sup.3 is a side-chain of a naturally occurring amino acid or a side chain of a naturally occurring amino acid substituted with a halogen, hydroxyl, sulfonate, C1-C3 alkyl, C1-C3 alkoxy or acyl;
• R.sup.4 and R.sup.5 are each independently selected from the group consisting of --H, alkyl, aryl, nitrile and alkoxycarbonyl;
• and
• each R.sup.10 is independently selected from the group consisting of hydrogen, lower alkyl, halo-substituted lower alkyl, alkaryl, arylalkyl, aryl and heteroaralkyl radicals,
• from a 3-amino-3-substituted-2-oxo-1-nitropropane represented by the following structural formula:
• ##STR16## comprising the steps of:
• a) reacting said 3-amino-3-substituted-2-oxo-1-nitropropane with a carbonyl reducing agent, whereby the carbonyl group is reduced to form a 1-nitro-3-amino-3-substituted-2-propanol compound represented by the following structural formula:
• ##STR17## b) reacting said 1-nitro-3-amino-3-substituted-2-propanol with a nitro reducing agent, whereby the nitro group is reduced to form a first chemical intermediate represented by the following structural formula:
• ##STR18## c) reacting said first chemical intermediate with an aldehyde or a ketone, having a formula R.sup.10 (O)R.sup.10, in an anhydrous solvent, whereby R.sup.10 (O)R.sup.10 is condensed to form an imino compound;
• and
• d) reacting said imino compound with an imino reducing agent whereby the the first chemical intermediate is reductively aminated, thereby forming said protease inhibitor synthetic intermediate.