Methods Of Preparing Thiazolidines
The present invention provides methods of preparing thiazolidines, and in particular methods of preparing ribose-cysteine.
1 . A method of preparing a thiazolidine comprising:
a) contacting a sugar and a cysteine with an aqueous solution under suitable conditions to form the thiazolidine;
b) isolating the thiazolidine; and
c) optionally drying the thiazolidine for a sufficient period of time to yield an anhydrous thiazolidine.
2 . The method of claim 1 wherein the sugar is aldose or ketose monosaccharide, wherein said aldose or ketose monosaccharide is glyceraldehyde, glucose, ribose, or fructose.
3 . The method of claim 1 wherein the cysteine is free of cystine.
4 . The method of claim 1 wherein:
a) the sugar is contacted with the aqueous solution before the cysteine is contacted with the aqueous solution; or
b) wherein the cysteine is contacted with the solution after the sugar is completely dissolved.
5 . The method of claim 1 further comprising contacting the solution with an alcohol.
6 . The method of claim 5 wherein cysteine and an alcohol are contacted with the solution after the sugar is completely dissolved or the cysteine and an alcohol are contacted with the solution simultaneously.
7 . The method of claim 6 wherein the method comprises in the following order:
i) contacting the sugar with the aqueous solution to form a sugar solution;
ii) contacting the cysteine with the sugar solution of i); and
iii) contacting the alcohol with the solution of ii).
8 . The method of claim 1 wherein the isolating comprises precipitating the thiazolidine, wherein the thiazolidine is precipitated by contacting the solution with an alcohol and optionally, wherein the precipitated thiazolidine is washed with a washing agent.
9 . The method of claim 1 wherein the method yields at least 95% of a calculated theoretical yield and/or the thiazolidine is at least 99% pure as determined by HPLC.
10 . The method of claim 1 wherein the thiazolidine comprises less than 225 ppm of an alcohol.
11 . The method of claim 1 wherein the isolated thiazolidine comprises a monohydrate thiazolidine.
12 . The method of claim 1 wherein the isolated thiazolidine consists of anhydrous thiazolidine.
13 . The method of claim 1 wherein the thiazolidine is RibCys, GlcCys, GlycCys, FruCys, GlcNH 2 Cys, GlcNHAcCys, and/or any combination thereof.
14 . A method of preparing a thiazolidine comprising:
a) contacting an aldose or ketose monosaccharide or an amino sugar, and a cysteine with an aqueous solution under conditions to form the thiazolidine;
b) precipitating the thiazolidine; and
c) vacuum drying the thiazolidine at a temperature that is less than or equal to 65° C.,
wherein the aqueous solution optionally comprises ethanol.
15 . The method of claim 14 wherein the thiazolidine is RibCys, GlcCys, GlycCys, FruCys, GlcNH 2 Cys, GlcNHAcCys, and/or any combination thereof.
16 . A method of preparing a thiazolidine comprising in the following order:
a) contacting an aldose or ketose monosaccharide or an amino sugar with an aqueous solution;
b) contacting the solution of step a) with a cysteine and ethanol;
c) precipitating the solution of step b) to yield a thiazolidine precipitate; and
d) vacuum drying the thiazolidine precipitate.
17 . The method of claim 16 wherein step b) comprises in the following order:
i) contacting the solution of step a) with the cysteine; and
ii) contacting the solution of step i) with the ethanol.
18 . The method of claim 16 wherein the thiazolidine is RibCys, GlcCys, GlycCys, FruCys, GlcNH 2 Cys, GlcNHAcCys, and/or any combination thereof.