Method of preparing sphingosine derivatives

A method of preparing a threo-isomer of a derivative of sphingosine, wherein said derivative of sphingosine comprises the formula:

• ##STR15## wherein X and Y are selected from the group consisting essentially of hydrogen, hydroxyl, alkoxy, amino, alkylamino and dialkylamino and wherein R.sub.1 is selected from the group consisting essentially of hydrogen, alkyl and aryl, comprising:
• a) reducing serine methyl ester by a hydride reagent to from an aldehyde or aldehyde derivative that is capable of forming said derivative of sphingosine in substantially the same manner as said aldehyde, said aldehyde having the formula:
• ##STR16## b) adding acetylide anions to said aldehyde or aldehyde derivative to form an erythro-isomer of propargyl alcohol;
• c) inverting said propargyl alcohol by S.sub.N 2 inversion to form a threo-isomer of propargyl alcohol;
• d) acidifying said threo-isomer to form a diol having the formula:
• ##STR17## wherein R is selected from the group consisting essentially of hydrogen, alkyl and aryl;
• e) cleaving said diol to form an amine having the formula:
• ##STR18## f) reducing said amine to form an alkene having the formula:
• ##STR19## and g) adding a functional group selected from the group consisting of hydrogen, hydroxyl, alkoxy, amino, alkylamino, and dialkylamino to the 4 and 5 position of said alkene to form said threo-isomer of a derivative of sphingosine.

A method of preparing an erythro isomer of a derivative of sphingosine, wherein said derivative of sphingosine comprises the formula:

• ##STR22## wherein X and Y are selected from the group consisting essentially of hydrogen, hydroxyl, alkoxy, amino, alkylamino and dialkylamino and wherein R.sub.1 is selected from the group consisting essentially of hydrogen, alkyl and aryl, comprising the steps of:
• a) adding acetylide anions to an aldehyde or a derivative of said aldehyde that is capable of forming said derivative of sphingosine in substantially the same manner as said aldehyde to form an erythro-isomer of propargyl alcohol, said aldehyde having the formula:
• ##STR23## b) acidifying said propargyl alcohol to form a diol having the formula:
• ##STR24## wherein R is selected from the group consisting essentially of hydrogen, alkyl and aryl;
• c) cleaving said diol to form an amine having the formula:
• ##STR25## d) reducing said amine to form an alkene having the formula:
• ##STR26## and e) adding a functional group selected from the group consisting of hydrogen, hydroxyl, alkoxy, amino, alkylamino, and dialkylamino to the 4 and 5 position of said alkene to form said erythro-isomer of a derivative of sphingosine.

A method of preparing an erythro isomer of a derivative of sphingosine, wherein said derivative of sphingosine comprises the formula:

• ##STR28## wherein X and Y are selected from the group consisting essentially of hydrogen, hydroxyl, alkoxy, amino, alkylamino and dialkylamino and wherein R.sub.1 is selected from the group consisting essentially of hydrogen, alkyl and aryl, comprising:
• a) reducing serine methyl ester by a hydride reagent to form an aldehyde or aldehyde derivitive that is capable of forming said derivative of sphingosine in substantially the same manner as said aldehyde, said aldehyde having the formula:
• ##STR29## b) adding acetylide anions to an aldehyde or aldehyde derivative to form an erythro-isomer of propargyl alcohol;
• c) acidifying said erythro-isomer to form a diol having the formula:
• ##STR30## wherein R is selected from the group consisting essentially of hydrogen, alkyl and aryl;
• d) cleaving said diol to form an amine having the formula:
• ##STR31## e) reducing said amine to form an alkene having the formula:
• ##STR32## and f) adding a functional group selected from the group consisting of hydrogen, hydroxyl, alkoxy, amino, alkylamino, and dialkylamino to the 4 and 5 position of said alkene to form said erythro-isomer of a derivative of sphingosine.

A method of preparing a threo-isomer of sphingosine or a derivative thereof, wherein said derivative of sphingosine comprises the formula:

• ##STR34## wherein R.sub.1 is selected from the group consisting essentially of hydrogen, alkyl and aryl, comprising the steps of:
• a) adding acetylide anions to an aldehyde or a derivative of said aldehyde that is capable of forming said sphingosine or derivative thereof in substantially the same manner as said aldehyde to form an erythro-isomer of propargyl alcohol, said aldehyde having the formula:
• ##STR35## b) inverting said propargyl alcohol by S.sub.N 2 inversion to form a threo-isomer of propargyl alcohol;
• c) acidifying said threo-isomer to form a diol having the formula:
• ##STR36## wherein R is selected from the group consisting essentially of hydrogen, alkyl and aryl;
• d) cleaving said diol to form an amine having the formula:
• ##STR37## and e) reducing said amine to form an alkene having the formula:
• ##STR38##

A method of preparing an erythro-isomer of sphingosine or a derivative thereof, wherein said derivative of sphingosine comprises the formula:

• ##STR40## wherein R.sub.1 is selected from the group consisting essentially of hydrogen, alkyl and aryl, comprising the steps of:
• a) adding acetylide anions to an aldehyde or a derivative of said aldehyde that is capable of forming said sphingosine or derivative thereof in substantially the same manner as said aldehyde to form an erythro-isomer of propargyl alcohol, said aldehyde having the formula:
• ##STR41## b) acidifying said propargyl alcohol to form a diol having the formula:
• ##STR42## wherein R is selected from the group consisting essentially of hydrogen, alkyl and aryl;
• c) cleaving said diol to form an amine having the formula:
• ##STR43## and d) reducing said amine to form an alkene having the formula:
• ##STR44##