Synthesis of 2-alkyl amino acids
OwnerMukund Chorghade, Mukund Gurjar +1inventors
InventorsMukund Chorghade, Mukund Gurjar, Bhanu Chanda
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Abstract
A method of preparing a 2-alkyl amino acid involves the aziridination of an alkylacrylate and the opening of the aziridine ring by addition of a side chain. This method can result in the preparation of enantiomeric excess of a 2-alkyl amino acid. The invention also discloses a method of preparing a class of iron chelating agents related to desferrithiocin, all of which contain a thiazoline ring. In this method, an aryl nitrile or imidate is condensed with cysteine, a 2-alkyl cysteine, or a cysteine ester.
Claims19
1-17. (canceled)
A method of preparing a compound represented by Structural Formula (VI):
- or a salt thereof;
- wherein:
- R6 and R7 are, independently, —H or a substituted or unsubstituted alkyl group;
- comprising the steps of:
- a.) aziridinating a compound represented by Structural Formula (VII):
- by reacting said compound with a source of nitrogen and an aziridination catalyst, thereby forming a compound represented by Structural Formula (VIII):
- wherein:
- L is a bond, sulfoxide (—S(O)—), or sulfone (—S(O)(O)—);
- R9 is a substituted or unsubstituted alkyl group or a substituted or unsubstituted aryl group;
- and
- R6 and R7 are as defined above;
- b.) reacting the compound represented by Structural Formula (VIII) with a nucleophile, A-S-Z, wherein A is —H;
- and Z is —H or a protecting group;
- thereby forming a compound represented by Structural Formula (IX):
- c.) cleaving Z and L-R9 from the compound represented by Structural Formula (IX), thereby forming the compound represented by Structural Formula (VI).
A method of preparing a compound represented by Structural Formula (XI):
- or a salt thereof;
- wherein:
- R11 and R12 are, independently, —H or a substituted or unsubstituted alkyl group;
- R13 is —H, —(CH2)nSH, —(CH2)nOH, —(CH2)nNH2, —COOH, —CONH2, a substituted or unsubstituted alkyl group, a substituted or unsubstituted aromatic group, or a substituted or unsubstituted heteroaromatic group;
- and
- x is an integer from 0-12;
- comprising the steps of:
- a.) aziridinating a compound represented by Structural Formula (XII):
- by reacting said compound with a source of nitrogen and a stereospecific aziridination catalyst, thereby forming a compound represented by Structural Formula (XIII):
- wherein:
- L is a bond, sulfoxide (—S(O)—), or sulfone (—S(O)(O)—);
- R14 is a substituted or unsubstituted alkyl group or a substituted or unsubstituted aryl group;
- and
- R11 and R12 are as defined above;
- b.) reacting the compound represented by Structural Formula (XIII) with a nucleophile, A-R13, wherein A is —H, —Li, —MgCl, —MgBr, or —MgI, provided that A and R13 are not each —H;
- and R13 is as defined above;
- thereby forming a compound represented by Structural Formula (XIV):
- c.) cleaving L-R14 and optionally the protecting group of R13 from the compound represented by Structural Formula (XIV), thereby forming the compound represented by Structural Formula (XI).
A method of preparing a compound represented by Structural Formula (XVI):
- comprising the steps of:
- a) reacting the compound represented by Structural Formula (XVIII):
- wherein:
- L is a bond, sulfoxide (—S(O)—), or sulfone (—S(O)(O)—);
- and
- R17 is a substituted or unsubstituted alkyl group or a substituted or unsubstituted aryl group;
- with a nucleophile, A-S-Z, wherein A is —H;
- and Z is —H or a protecting group;
- thereby forming a compound represented by Structural Formula (XIX):
- b) cleaving R16, Z, and L-R17 from the compound represented by Structural Formula (XIX), thereby forming 2-methylcysteine or a salt thereof;
- c) resolving the enantiomers of 2-methylcysteine or salts thereof;
- d) isolating (S)-2-methylcysteine or a salt thereof, and neutralizing the salt, if present;
- and
- e) coupling (S)-2-methylcysteine with 2,4-dihydroxybenzonitrile, thereby forming the compound represented by Structural Formula (XVI)
Dependencies are inferred from the claim text.