Method preparing amino acid-derived diaminopropanols

A method for forming a 1,3-diamino-3-substituted-2-propanol chemical intermediate represented by the structural formula ##STR14## or salts thereof, wherein:

• R.sup.1 is an amino protecting group;
• R.sup.2 is selected from the group consisting of --H, C1-C18 alkyl, aryl, acetyl and tosyl;
• R.sup.3 is a side-chain of an amino acid wherein said side-chain is located .alpha. to the amino group of the amino acid, and wherein said amino acid is selected from the group consisting of alanine, cysteine, 3,5-dibromotyrosine, 3,5-diiodotyrosine, glutamine, glycine, histidine, hydroxylysine, isoleucine, leucine, methionine, phenylalanine, serine, threonine, thyroxine, tryptophane, tyrosine, valine and .alpha.-aminobutyric acid;
• and
• R.sup.4 and R.sup.5 are each independently selected from the group consisting of --H, alkyl, aryl, nitrile and alkoxycarbonyl,
• from an amino acid comprising the steps of:
• a) reacting as obviously intended said amino acid with an activating component and an aprotic solvent under anhydrous conditions to form an activated amino acid;
• b) reacting, as obviously intended an anhydrous base with a nitromethane compound to form a nitromethane anion solution;
• c) reacting, as obviously intended said activated amino acid with the nitromethane anion solution under anhydrous conditions to form a 3-amino-3-substituted-2-oxo-1-nitropropane;
• d) reacting, as obviously intended said 3-amino-3-substituted-2-oxo-1-nitropropane with a carbonyl reducing agent, thereby forming a 1-nitro-3-amino-3-substituted-2-propanol compound;
• and
• e) contacting said 1-nitro-3-amino-3-substituted-2-propanol with a nitro reducing agent, thereby forming said 1,3-diamino-3-substituted-2-propanol chemical intermediate.

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

• R.sup.1 is an amino 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 an amino acid wherein said side-chain is located .alpha. to the amino group of the amino acid, and wherein said amino acid is selected from the group consisting of alanine, cysteine, 3,5-dibromotyrosine, 3,5-diiodotyrosine, glutamine, glycine, histidine, hydroxylysine, isoleucine, leucine, methionine, phenylalanine, serine, threonine, thyroxine, tryptophane, tyrosine, valine and .alpha.-aminobutyric acid;
• R.sup.4 and R.sup.5 are each independently selected from the group consisting of --H, alkyl, aryl, nitrile and alkoxycarbonyl;
• and
• R.sup.7 is selected from the group consisting of alkyl, hydroxyalkyl, alkoxyalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, heteroaralkyl, and aminoalkyl radicals,
• from a 3-amino-3-substituted-2-oxo-1-nitropropane, comprising the steps of:
• a) reacting obviously intended said 3-amino-3-substituted-2-oxo-1-nitropropane with a carbonyl reducing agent, thereby forming a 1-nitro-3-amino-3-substituted-2-propanol compound;
• b) reacting obviously intended said 1-nitro-3-amino-3-substituted-2propanol with a nitro reducing agent, thereby forming a first chemical intermediate;
• c) reacting, as obviously intended said first chemical intermediate with X.sup.1 --R.sup.7, wherein X.sup.1 is a halogen radical, and with a base, thereby forming said protease inhibitor synthetic intermediate.

A method for producing a protease inhibitor synthetic intermediate represented by the formula ##STR16## or salts thereof, wherein:

• R.sup.1 is an amino 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 an amino acid wherein said side-chain is located .alpha. to the amino group of the amino acid, and wherein said amino acid is selected from the group consisting of alanine, cysteine, 3,5-dibromotyrosine, 3,5-diiodotyrosine, glutamine, glycine, histidine, hydroxylysine, isoleucine, leucine, methionine, phenylalanine, serine, threonine, thyroxine, tryptophane, tyrosine, valine and .alpha.-aminobutyric acid;
• R.sup.4 and R.sup.5 are each independently selected from the group consisting of --H, alkyl, aryl, nitrile and alkoxycarbonyl;
• and
• R.sup.7 is selected from the group consisting of alkyl, hydroxyalkyl, alkoxyalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, heteroaralkyl, and aminoalkyl radicals,
• from a 3-amino-3-substituted-2-oxo-1-nitropropane, comprising the steps of:
• a) reacting said 3-amino-3-substituted-2-oxo-1-nitropropane with a carbonyl reducing agent, thereby forming a 1-nitro-3-amino-3-substituted-2-propanol compound;
• b) reacting said 1-nitro-3-amino-3-substituted-2-propanol with a nitro reducing agent, thereby forming a first chemical intermediate;
• c) reacting said first chemical intermediate with dimethyl sulfoxide and oxalyl chloride to form a reaction mixture;
• and
• d) reacting said reaction mixture with a base, thereby forming said protease inhibitor synthetic intermediate.