Optically pure and enriched isomers of chelating ligands and contrast agents
OwnerJohn Amedio, Peter Caravan +5inventors
InventorsJohn Amedio, Peter Caravan, Vincent Jacques, Kevin Zhou, Stuart Levy, Shirley Kalogeropoulos, Matthew Greenfield
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Abstract
Organic chelating ligands, organic chelating ligand precursors, and metal chelates are disclosed. Methods for synthesizing the same are also described, including methods for preparing optically-enriched or optically-pure compositions of the same.
Claims37
A composition comprising an organic chelating ligand having a formula selected from the group consisting of:
- where n can range from 1 to 4, and wherein said composition has an enantiomeric excess of greater than 50% of an (R) isomer at the 2 position of said chelating ligand.
A composition comprising an organic chelating ligand having a formula selected from the group consisting of:
- where n can range from 1 to 4, and wherein said composition has an enantiomeric excess of greater than 50% of an (S) isomer at the 2 position of said chelating ligand.
A composition comprising a metal chelate having a structure:
- said composition having an enantiomeric excess of greater than 50% of an (R) isomer of said chelate at the 2 position, wherein n can range from 1 to 4, and wherein M can be selected from the group consisting of:
- Gd(III), Fe(III), Mn(II), Mn(III), Cr(III), Cu(II), Dy(III), Ho(III), Er(III), Eu(III), Tb(II), Tb(III), Ce(III), Pr(III), Yb(III), Tm(III), Nd(III), and Tb(IV).
A composition comprising a metal chelate having a structure:
- said composition having an enantiomeric excess of greater than 50% of an (S) isomer at the 2 position of said chelate, wherein n can range from 1 to 4, and wherein M can be selected from the group consisting of:
- Gd(III), Fe(III), Mn(II), Mn(III), Cr(III), Cu(II), Dy(III), Ho(III), Er(III), Eu(III), Tb(II), Tb(III), Ce(III), Pr(III), Yb(III), Tm(III), Nd(III), and Tb(IV).
A composition comprising an organic chelating ligand precursor having a structure selected from the group consisting of:
- where n can range from 1 to 4, and wherein said composition has an enantiomeric excess of greater than 50% of an (R) isomer at the 2 position of said precursor.
A composition comprising an organic chelating ligand precursor having a structure selected from the group consisting of:
- where n can range from 1 to 4, and wherein said composition has an enantiomeric excess of greater than 50% of an (S) isomer at the 2 position of said precursor.
A method for synthesizing an organic chelating ligand precursor comprising:
- a) reacting a starting material compound having the structure:
- said starting material compound having an L-stereochemistry at the Cat carbon, where n can range from 1 to 4, to form a lactone;
- b) opening said lactone to yield a hydroxy-dioic acid ester;
- c) activating said hydroxy group of said hydroxy-dioic acid ester;
- and
- d) reacting said activated hydroxy group with an amine compound under conditions capable of alkylating said amine compound at one or more amine moieties to form an organic chelating ligand precursor, said organic chelating ligand precursor comprising one or more amine moieties.
A method for synthesizing an organic chelating ligand precursor comprising:
- a) reacting a starting material compound having the structure:
- said starting material compound having a D stereochemistry at the Cα carbon, where n can range from 1 to 4, to form a lactone;
- b) opening said lactone to yield a hydroxy-dioic acid ester;
- c) activating said hydroxy group of said hydroxy-dioic acid ester;
- and
- d) reacting said activated hydroxy group with an amine compound under conditions capable of alkylating said amine compound at one or more amine moieties to form an organic chelating ligand precursor, said organic chelating ligand precursor comprising one or more amine moieties.
A method for converting an organic chelating ligand comprising one or more carboxylic acid esters to a metal chelate comprising:
- a) providing said organic chelating ligand;
- b) deprotecting one or more of said one or more carboxylic acid esters of said organic chelating ligand to yield one or more carboxylic acid moieties;
- and
- c) chelating a metal ion to result in said metal chelate;
- wherein said deprotection and said chelating steps are performed without purification of intermediates.
A method for converting an organic chelating ligand precursor to a metal chelate comprising:
- a) providing said organic chelating ligand precursor, said organic chelating ligand precursor comprising one or more amines;
- b) providing a carboxylic acid ester having a leaving group located at the α-carbon;
- c) reacting said carboxylic acid ester with said precursor under conditions in which one or more of said one or more amines of said precursor are alkylated to form an organic chelating ligand;
- and
- d) chelating a metal ion to said organic chelating ligand to result in a metal chelate;
- wherein said reacting and said chelating steps are performed without purification of intermediates.
A composition comprising an activated ester of an organic chelating ligand, said activated ester having a structure selected from the group consisting of:
- wherein n can range from 1 to 4, wherein X is selected from the group consisting of:
- and wherein said composition has an enantiomeric excess of greater than 50% of an (R) isomer at the 2 position of said chelating ligand.
A composition comprising an activated ester of an organic chelating ligand, said activated ester having a structure selected from the group consisting of:
- wherein n can range from 1 to 4, wherein X is selected from the group consisting of:
- and wherein said composition has an enantiomeric excess of greater than 50% of an (S) isomer at the 2 position of said chelating ligand.
A composition comprising an activated ester of a metal chelate having the following general formula:
- where n can range from 1 to 4 and X can be selected from the group consisting of:
- and wherein said composition has an enantiomeric excess of greater than 50% of an (R) isomer at the 2 position of said activated ester metal chelate.
A composition comprising an activated ester of a metal chelate having the following general formula:
- where n can range from 1 to 4 and X can be selected from the group consisting of:
- and wherein said composition has an enantiomeric excess of greater than 50% of an (S) isomer at the 2 position of said activated ester metal chelate.
A composition comprising a compound having the structure of Compound 26, 28, or 30, wherein said composition has an enantiomeric excess of greater than 50% of an (R) isomer at the 2 position of each conjugated chelating ligand or metal chelate.
A composition comprising a compound having the structure of Compound 26, 28, or 30, wherein said composition has an enantiomeric excess of greater than 50% of an (S) isomer at the 2 position of each conjugated chelating ligand or metal chelate.
Dependencies are inferred from the claim text.