Synthesis of chiral 2-alkyl amino acids

A method of preparing a compound represented by Structural Formula (I):

• or salts thereof;
• wherein, R1 is —H or a substituted or unsubstituted alkyl group;
• and
• R2 is a substituted or unsubstituted C1-C4 alkyl group;
• comprising the steps of:
• a) reacting a compound represented by Structural Formula (II):
• wherein R3 is —OH, a substituted or unsubstituted alkyloxy group, or a halogen;
• with a substituted or unsubstituted benzoic acid, thereby forming a substituted thiazoline represented by Structural Formula (III):
• wherein Ar is a substituted or unsubstituted phenyl group and R3 is as defined above;
• b) reacting the substituted thiazoline with a substituted oxazolidinone represented by Structural Formula (IV):
• wherein X is an aryl or an arylalkyl group, thereby forming a compound represented by Structural Formula (V):
• c) alkylating the product of step (b) with R2Y in the presence of a base in a polar, aprotic solvent, wherein R2 is as defined above and Y is a leaving group;
• thereby forming a compound represented by Structural Formula (VI):
• wherein R2 is as defined above;
• and
• d) hydrolyzing the product of step (c), thereby forming the compound represented by Structural Formula (I).

A method of preparing a compound represented by Structural Formula (VII):

• or salts thereof;
• wherein, R1 is —H or a substituted or unsubstituted alkyl group;
• and
• R2 is a substituted or unsubstituted C1-C4 alkyl group;
• comprising the steps of:
• a) reacting a compound represented by Structural Formula (VIII):
• wherein R3 is —OH, a substituted or unsubstituted alkyloxy group, or a halogen;
• with a substituted or unsubstituted benzoic acid, thereby forming a substituted thiazoline represented by Structural Formula (IX):
• wherein Ar is a substituted or unsubstituted phenyl group and R3 is as defined above;
• b) reacting the substituted thiazoline with a substituted oxazolidinone represented by Structural Formula (X):
• wherein X is an aryl or an arylalkyl group, thereby forming a compound represented by Structural Formula (XI):
• c) alkylating the product of step (b) with R2Y in the presence of a base in a polar, aprotic solvent, wherein R2 is as defined above and Y is a leaving group;
• thereby forming a compound represented by Structural Formula (XII):
• wherein R2 is as defined above;
• and
• d) hydrolyzing the product of step (c), thereby forming the compound represented by Structural Formula (VII).

A method of preparing a compound represented by Structural Formula (VII):

• comprising the steps of:
• a) reacting a compound represented by Structural Formula (II):
• wherein R3 is —OH, a substituted or unsubstituted alkyloxy group, or a halogen;
• with a substituted or unsubstituted benzoic acid, thereby forming a substituted thiazoline represented by Structural Formula (III):
• wherein Ar is a substituted or unsubstituted phenyl group and R3 is as defined above;
• b) reacting the substituted thiazoline with a substituted oxazolidinone represented by Structural Formula (IV):
• wherein X is an aryl or an arylalkyl group, thereby forming a compound represented by Structural Formula (V):
• c) alkylating the product of step (b) with R2Y in the presence of a base in a polar, aprotic solvent, wherein R2 is methyl and Y is a leaving group;
• thereby forming a compound represented by Structural Formula (VI):
• wherein R2 is methyl;
• and
• d) hydrolyzing the product of step (c), thereby forming the compound represented by Structural Formula (I):
• or salt thereof, where R1 is —H or a substituted or unsubstituted alkyl group, and
• R2 is methyl, and neutralizing the salt, if present;
• e) isolating the (S)-enantiomer from the enantiomers of the product of step (d);
• and
• f) coupling the (S)-enantiomer with 2,4-dihydroxybenzonitrile, thereby forming the compound represented by Structural Formula (VII).