US 2021/0380503 A1 · METHOD FOR THE STEREOISOMERIZATION OF CHIRAL COMPOUNDS

Abstract

The present invention provides a novel method for the controlled stereoisomerization (comprising the stereo-conversion of chiral compounds to racemates, non-racemic mixtures and mixtures of epimers). The method of the invention provides the fully controlled generation of mixtures of different ratios of (S) and (R) stereoisomers, both enantiomers and diastereomers, of a given compound or a mixture of compounds. Such mixtures and isotopically labeled variants of said mixtures provided by the present invention are useful as an authenticity or external or internal standards in various biochemical and medical applications. Further, with the method of the invention it is possible to generate specific stereoisomers from some amino acids as well as degradation and oxidation products thereof which were previously not available. Thence, the invention provides in additional aspects the generation of a group of previously unavailable stereoisomers (enantiomers, epimers, and mixtures thereof such as a racemate) with amino acid type structures.

Claims21

Dependent claims

A method for the stereoisomerization (racemization or epimerization) of a chiral compound, the method comprising the steps:

a) providing a mixture comprising:
(aa) the chiral compound which contains at least one stereogenic carbon atom;
(bb) a stereoisomerization tag;
and
(cc) optionally a buffer;
and
(b.1) heating the mixture to a temperature from 50 to 200° C. for 30 minutes to 24 hours;
or
(b.2) treating the mixture in a microwave at 200 to 400 W for 1 min to 6 h, at a temperature from 50 to 300° C.

6 more elements

A compound, which is a stereoisomer, selected from:

(i) a proteinogenic amino acids selected from D-13C5,15N-Valine, D-13C6-Leucine, D-13C6,15N-Leucine, D-13C6-Isoleucine, D-13C6,15N-Isoleucine, DL-13C6-Isoleucine, DL-13C6,15N-Isoleucine, D-13C5-Methionine, D-13C5,15N-Methionine, DL-13C5-Methionine, DL-13C5,15N-Methionine, D-13C5-Proline, D-13C5,15N-Proline, DL-13C5-Proline, D-13C3-Serine, D-13C3,15N-Serine, D-13C4-Threonine, D-13C4,15N-Threonine, DL-13C4-Threonine, DL-13C4,15N-Threonine, D-13C3-Cystein, D-13C3,15N-Cystein, D-13C6-Cystine, D-13C6,15N-Cystine, D-13C9-Phenylalanine, DL-13C9-Tyrosine, DL-13C9,15N-Tyrosine, D-13C11-Tryptophane, D-13C11,15N2-Tryptophane, DL-13C11-Tryptophane, DL-13C11, 15N2-Tryptophane, DL-13C5,15N-Glutamic acid, D-13C4,15N-Aspartic acid, DL-13C4,15N-Aspartic acid, D-13C5-Glutamine, DL-13C5-Glutamine, DL-13C5,15N-Glutamine, DL-13C5,15N2-Glutamine, D-13C4,15N2-Asparagine, DL-13C4-Asparagine, DL-13C4,15N-Asparagine, DL-13C4,15N2-Asparagine, D-13C6-Histidine, D-13C6,15N-Histidine, D-13C6,15N2-Histidine, D-13C6,15N3-Histidine, DL-13C6-Histidine, DL-13C6,15N-Histidine, DL-13C6,15N2-Histidine, DL-13C6,15N3-Histidine, D-13C6,15N-Lysine, D-13C6,15N2-Lysine, DL-13C6,15N-Lysine, DL-13C6,15N2-Lysine, D-13C6-Arginine, D-13C6,15N-Arginine, D-13C6,15N2-Arginine, D-13C6,15N3-Arginine, D-13C6,15N4-Arginine, DL-13C6-Arginine, DL-13C6,15N-Arginine, DL-13C6,15N2-Arginine, DL-13C6,15N3-Arginine;
(ii) an oxidation product selected from Met:
L-13C5,15N-Methionine sulfoxide (S—(S)), L-13C5,15N-Methionine sulfoxide (S—(R)), D-13C5,15N-Methionine sulfoxide (R—(S)), D-13C5,15N-Methionine sulfoxide (R—(R)), DL-13C5,15N-Methionine sulfoxide (RS—(S)), DL-13C5,15N-Methionine sulfoxide (RS—(R)), L-13C5,15N,18O-Methionine sulfoxide (S—(S)), L-13C5,15N,18O-Methionine sulfoxide (S—(R)), D-13C5,15N,18O-Methionine sulfoxide (R—(S)), D-13C5,15N,18O-Methionine sulfoxide (R—(R)), DL-13C5,15N,18O-Methionine sulfoxide (RS—(S)), DL-13C5,15N,18O-Methionine sulfoxide (RS—(R)), L-13C5,15N-Methionine sulfone (S), D-13C5,15N-Methionine sulfone (R), DL-13C5,15N-Methionine sulfone (RS), L-13C5,15N,18O-Methionine sulfone (S), D-13C5,15N,18O-Methionine sulfone (R), DL-13C5,15N,18O-Methionine sulfone (RS), L-13C5,15N,18O2-Methionine sulfone (S), D-13C5,15N,18O2-Methionine sulfone (R), DL-13C5,15N,18O2-Methionine sulfone (RS), L-13C5-Methionine sulfoxide (S—(S)), L-13C5-Methionine sulfoxide (S—(R)), D-13C5-Methionine sulfoxide (R—(S)), D-13C5-Methionine sulfoxide (R—(R)), DL-13C5-Methionine sulfoxide (RS—(S)), DL-13C5-Methionine sulfoxide (RS—(R)), L-13C5,18O-Methionine sulfoxide (S—(S)), L-13C5,18O-Methionine sulfoxide (S—(R)), D-13C5,18O-Methionine sulfoxide (R—(S)), D-13C5,18O-Methionine sulfoxide (R—(R)), DL-13C5,18O-Methionine sulfoxide (RS—(S)), DL-13C5,18O-Methionine sulfoxide (RS—(R)), L-13C5-Methionine sulfone (S), D-13C5-Methionine sulfone (R), DL-13C5-Methionine sulfone (RS), L-13C5,18O-Methionine sulfone (S), D-13C5,18O-Methionine sulfone (R), DL-13C5,18O-Methionine sulfone (RS), L-13C5,18O2-Methionine sulfone (S), D-13C5,18O2-Methionine sulfone (R), DL-13C5,18O2-Methionine sulfone (RS);
(iii) a decomposition product selected from Trp:
L-13C10,15N2-Kynurenine, D-13C10,15N2-Kynurenine, DL-13C10,15N2-Kynurenine, L-13C10,15N-Kynurenine, D-13C10,15N-Kynurenine, DL-13C10,15N-Kynurenine, L-13C10-Kynurenine, D-13C10-Kynurenine, DL-13C10-Kynurenine;
(iv) an uncommon amino acid selected from D-13C6-allo-Isoleucine, D-13C6,15N-allo-Isoleucine, DL-13C6-allo-Isoleucine, DL-13C6,15N-allo-Isoleucine, D-13C4-allo-Threonine, D-13C415N-allo-Threonine, DL-13C4-allo-Threonine, DL-13C415N-allo-Threonine, D-13C4-Homoserine, D-13C415N-Homoserine, DL-13C4-Homoserine, DL-13C415N-Homoserine, D-13C4,15N-Homocystein, D-13C4-Homocystein, DL-13C4,15N-Homocystein, DL-13C4-Homocystein, D-13C815N2-Homocystine, D-13C815N-Homocystine, D-13C8-Homocystine, DL-13C8N2-Homocystine, DL-13C8N-Homocystine, DL-13C8-Homocystine, D-13C5,15N2-Ornithine, D-13C5,15N-Ornithine, D-13C5-Ornithine, DL-13C5,15N2-Ornithine, DL-13C5,15N-Ornithine, DL-13C5-Ornithine, D-13C6,15N3-Citrulline, D-13C6,15N2-Citrulline, D-13C6,15N-Citrulline, D-13C6-Citrulline, DL-13C6,15N3-Citrulline, DL-13C6,15N2-Citrulline, DL-13C6,15N-Citrulline, DL-13C6-Citrulline, D-13C5,15N-Norvaline, D-13C5-Norvaline, DL-13C5,15N-Norvaline, DL-13C5-Norvaline, D-13C6,15N-Norleucine, D-13C6-Norleucine, DL-13C6,15N-Norleucine, DL-13C6-Norleucine, D-13C4,15N-2-Aminobutyric acid, D-13C4-2-Aminobutyric acid, DL-13C4,15N-2-Aminobutyric acid, DL-13C4-2-Aminobutyric acid, D-13C4,15N-Aminoisobutyric acid, D-13C4-Aminoisobutyric acid, DL-13C4,15N-Aminoisobutyric acid, DL-13C4-Aminoisobutyric acid, D-13C10,15N3-Hypusine (R), D-13C10,15N3-Hypusine (S), D-13C10,15N2-Hypusine (R), D-13C10,15N2-Hypusine (S), D-13C10,15N-Hypusine (R), D-13C10,15N-Hypusine (S), DL-13C10,15N3-Hypusine (R), DL-13C10,15N3-Hypusine (S), DL-13C10,15N2-Hypusine (R), DL-13C10,15N2-Hypusine (S), DL-13C10,15N-Hypusine (R), DL-13C10,15N-Hypusine (S), D-13C10,15N3-Deoxyhypusine, D-13C10,15N2-Deoxyhypusine, D-13C10,15N-Deoxyhypusine, D-13C10-Deoxyhypusine, DL-13C10,15N3-Deoxyhypusine, DL-13C10,15N2-Deoxyhypusine, DL-13C10,15N-Deoxyhypusine, DL-13C10-Deoxyhypusine.

3 more elements

Dependencies are inferred from the claim text.

Method for the stereoisomerization of chiral compounds

Life of this patent

Method for the stereoisomerization of chiral compounds

Life of this patent

Abstract

Claims21