Preparation of Methionine or Selenomethionine from Homoserine via a Lactone Intermediate

Abstract

Provided herein are processes for the production of methionine or selenomethionine from homoserine. In particular, the processes proceed via the production of lactone intermediates.

1 . A process for preparing a compound comprising Formula (III) or a pharmaceutically acceptable salt thereof, the process comprising:
 a. contacting a compound comprising Formula (I) with an acyl donor comprising R to form a compound comprising Formula (IIb):   b. contacting the compound comprising Formula (IIb) with a compound comprising MeZ to form a compound comprising Formula (IIIb): and   c. contacting the compound comprising Formula (IIIb) with a deacylating agent to form the compound comprising Formula (III) or pharmaceutically acceptable salt thereof:   
       
         
           
           
               
               
           
         
         wherein:
 the compound comprising MeZ is an alkali metal methaneselenoate or methyl selenol; 
 Me is methyl; 
 R is chosen hydrogen, hydrocarbyl, and substituted hydrocarbyl; and 
 Z is selenium. 
 
       
     
     
         2 . The process of  claim 1 , wherein R is chosen from hydrogen, alkyl, alkene, alkoxy, aryl, substituted alkyl, substituted alkene, substituted alkoxy, and substituted aryl. 
     
     
         3 . The process of  claim 1 , wherein the acyl donor is chosen form an acyl halide, an acid anhydride, and a carbamate; and the molar ratio of the compound comprising Formula (I) to the acyl donor is from about 1:0.5 to about 1:10. 
     
     
         4 . The process of  claim 1 , wherein the reaction of step (a) further comprises a proton donor chosen from HCl, HBr, HI, HClO 3 , HClO 4 , HBrO 4 , HIO 3 , HIO 4 , HNO 3 , H 3 PO 4 , poly H 3 PO 4 , H 2 SO 4 , MeSO 3 H, CF 3 SO 3 H, and p-toluene sulfonic acid; and, optionally, further comprises a catalyst 
     
     
         5 . The process of  claim 1 , wherein the molar ratio of the compound comprising Formula (IIb) to the alkali metal methaneselenoate or methyl selenol is from about 1:0.5 to about 1:5. 
     
     
         6 . The process of  claim 1 , wherein the deacylating agent is a proton acceptor chosen from an alkali metal hydroxide, an alkaline earth metal hydroxide, a alkali metal carbonate, an amide, and a hydride; or the deacylating agent is a proton donor chosen from HCl, HBr, HI, HClO 3 , HClO 4 , HBrO 4 , HIO 3 , HIO 4 , HNO 3 , H 2 SO 4 , MeSO 3 H, CF 3 SO 3 H, and p-toluene sulfonic acid. 
     
     
         7 . The process of  claim 1 , wherein steps (a)-(c) are conducted in the presence of a solvent at a temperature of about 20° C. to about 100° C. and at ambient pressure; the solvent being chosen from an aprotic solvent, a protic solvent, and combinations thereof; and the molar ratio of the solvent to the compound comprising Formula (I) is from about 1:1 to about 50:1. 
     
     
         8 . The process of  claim 1 , wherein the compound comprising Formula (III) has an L configuration, a D configuration, or mixture thereof. 
     
     
         9 . The process of  claim 1 , wherein R is ethoxy; the acyl donor is chloroformate; the proton donor is hydrochloric acid; the compound comprising MeZ is lithium methyl selenide, and the deacylating agent is sodium hydroxide. 
     
     
         10 . A process for preparing a compound comprising Formula (III) or a pharmaceutically acceptable salt thereof, the process comprising:
 a. contacting a compound comprising Formula (I) with a proton donor (HX) to form a compound comprising Formula (II); and   b. contacting the compound comprising Formula (II) with a compound comprising MeZ to form the compound comprising Formula (III) or pharmaceutically acceptable salt thereof:   
       
         
           
           
               
               
           
         
         wherein:
 the compound comprising MeZ is chosen from an alkali metal methaneselenoate and methyl selenol; 
 Me is methyl; 
 X is an anion; and 
 Z is selenium. 
 
       
     
     
         11 . The process of  claim 10 , wherein the proton donor is chosen from HCl, HBr, HI, HClO 3 , HClO 4 , HBrO 4 , HIO 3 , HIO 4 , HNO 3 , H 2 SO 4 , MeSO 3 H, CF 3 SO 3 H, and p-toluene sulfonic acid; and the molar ratio of the compound comprising Formula (I) to the proton donor is from about 1:0.1 to about 1:10. 
     
     
         12 . The process of  claim 10 , wherein the step (a) is conducted in the presence of a protic solvent chosen from water, a C 104  alcohol, and combinations thereof; the molar ratio of the solvent to the compound comprising Formula (I) is from about 1:1 to about 50:1; and the reaction is conducted at a temperature from about 50° C. to about 150° C. 
     
     
         13 . The process of  claim 10 , wherein the molar ratio the compound comprising Formula (II) to the alkali metal methaneselenoate is from about 1:0.5 to about 1:10; the reaction is conducted in the presence a solvent chosen from an aprotic solvent, a protic solvent, and combinations thereof; the molar ratio of the solvent to the compound comprising Formula (II) is from about 1:1 to about 50:1; and the reaction is conducted at a temperature from about 20° C. to about 200° C., at ambient pressure, and under an inert gas chosen from nitrogen and argon. 
     
     
         14 . The process of  claim 10 , wherein the molar ratio the compound comprising Formula (II) to methyl selenol is from about 1:10 to about 1:150; the reaction is conducted in the presence of a solvent chosen from a protic solvent, an aprotic solvent, an organic solvent, and combinations thereof; the molar ratio of the solvent to the compound comprising Formula (IIa) is from about 1:1 to about 50:1; and the reaction is conducted at a temperature from about 20° C. to about 200° C., at ambient pressure, and under an inert gas chosen from nitrogen and argon. 
     
     
         15 . A process for preparing a compound comprising Formula (III) or a pharmaceutically acceptable salt thereof, the process comprising:
 a. contacting a compound comprising Formula (I) with a first proton donor (HX) to form a compound comprising Formula (II);   b. contacting the compound comprising Formula (II) with RC(O)R′ to form a compound comprising Formula (IIa);   c. contacting the compound comprising Formula (IIa) with a compound comprising MeZ to form a compound comprising Formula (IIIa) or a pharmaceutically acceptable salt thereof; and   d. contacting the compound comprising Formula (IIIa) or pharmaceutically acceptable salt thereof with a second proton donor to form the compound comprising Formula (III) or a pharmaceutically acceptable salt thereof:   
       
         
           
           
               
               
           
         
         wherein:
 Me is methyl; 
 R is hydrocarbyl or substituted hydrocarbyl; 
 R′ is hydrogen, hydrocarbyl, or substituted hydrocarbyl; 
 X is an anion; and 
 Z is sulfur or selenium. 
 
       
     
     
         16 . The process of  claim 15 , wherein R is chosen from alkyl, alkene, aryl, substituted alkyl, substituted alkene, and substituted aryl; and R′ is chosen from hydrogen, alkyl, alkene, aryl, substituted alkyl, substituted alkene, and substituted aryl. 
     
     
         17 . The process of  claim 15 , wherein the first proton donor is chosen from HCl, HBr, HI, HClO 3 , HClO 4 , HBrO 4 , HIO 3 , HIO 4 , HNO 3 , H 2 SO 4 , MeSO 3 H, CF 3 SO 3 H, and p-toluene sulfonic acid; and the molar ratio of the compound comprising Formula (I) to the first proton donor is from about 1:0.5 to about 1:5. 
     
     
         18 . The process of  claim 15 , wherein RC(O)R′ is chosen from acetaldehyde, propionaldehyde, benzaldehyde, propionaldehyde, acetophenone, and benzophenone; and the molar ratio of the compound comprising Formula (I) to RC(O)R′ is from about 1:0.1 to about 1:10. 
     
     
         19 . The process of  claim 15 , wherein steps (a) and (b) are conducted in the presence a solvent chosen from an aprotic solvent, a protic solvent, an organic solvent, and combinations thereof; the molar ratio of the solvent to the compound comprising Formula (I) is from about 1:1 to about 50:1; and steps (a) and (b) are conducted at a temperature from about 50° C. to about 150° C. 
     
     
         20 . The process of  claim 15 , wherein the compound comprising MeZ is chosen from an alkali metal methanethiolate, an alkali metal methaneselenoate, methyl mercaptan, and methyl selenol. 
     
     
         21 . The process of  claim 20 , wherein the molar ratio of the compound comprising Formula (IIa) to the alkali metal methanethiolate or the alkali metal methaneselenoate is from about 1:0.25 to about 1:5; the reaction is performed in the presence of a solvent chosen from an aprotic solvent, a protic solvent, and combinations thereof; the molar ratio of the solvent to the compound comprising Formula (IIa) is from about 1:1 to about 50:1; and the reaction is conducted at a temperature of about 20° C. to about 200° C., at ambient pressure, and under an inert gas chosen from nitrogen and argon. 
     
     
         22 . The process of  claim 20 , wherein the molar ratio the compound comprising Formula (IIa) to methyl mercaptan or methyl selenol is from about 1:10 to about 1:150; the reaction is performed in the presence of a solvent chosen from an aprotic solvent, a protic solvent, an organic solvent, and combinations thereof; the molar ratio of the solvent to the compound comprising Formula (IIa) is from about 1:1 to about 50:1; and the reaction is conducted at a temperature of about 20° C. to about 200° C., at ambient pressure, and under an inert gas chosen from nitrogen and argon. 
     
     
         23 . The process of  claim 15 , wherein the second proton donor is chosen from HCl, HBr, HI, HClO 3 , HClO 4 , HBrO 4 , HIO 3 , HIO 4 , HNO 3 , H 3 PO 4 , poly H 3 PO 4 , H 2 SO 4 , MeSO 3 H, CF 3 SO 3 H, and p-toluene sulfonic acid; and the molar ratio of the compound comprising Formula (IIIa) to the second proton donor is from about 1:0.5 to about 1:10. 
     
     
         24 . The process of  claim 15 , wherein step (d) is conducted in the presence of a protic solvent; the molar ratio of the solvent to the compound comprising Formula (IIIa) is from about 1:1 to about 50:1; and the reaction is conducted at a temperature of about 20° C. to about 100° C.