Method of producing an optically enriched tertiary alcohol from an epoxide using halohydrin dehalogenase
A process for the production of an optically enriched tertiary alcohol of the formula (2a) or (2b), by reacting an epoxide of the formula (1) with a nucleophilic agent Nu in the presence of halohydrin dehalogenase.
1. A process for the production of an optically enriched tertiary alcohol of formula (2a) or (2b), comprising reacting an epoxide of formula (1) with a nucleophilic agent Nu catalyzed by halohydrin dehalogenase
wherein R1 and R2 are chemically distinct and are independently selected from the group consisting of straight or branched alkyl groups having 1 to 15 carbon atoms and optionally substituted aryl groups, arylalkyl groups, alkenyl groups and cycloalkyl groups, and wherein Nu is selected from the group consisting of CN − , N 3 31 , NO 2 − , NO 3 − , SCN − , Cl − , Br − , I − , or HCOO − ;
and recovering the optically enriched alcohol.
2. The process of claim 1 , wherein R1 and R2 independently are —(CH 2 ) n —CH 3 , wherein n is 0 to 8; —C 6 H 5 ; —(CH 2 ) n —(C 6 H) 5 ; —C 6 H 11 ; or CH 2 CO 2 R3, wherein R3 is —CH 3 , —C 2 H 5 , or —C(CH 3 ) 3 .
3. The process of claim 1 , wherein the halohydrin dehalogenase is a polypeptide comprising the amino acid sequence of SEQ ID NOs: 1, 2, 3 or 4.
4. The process of claim 2 , wherein the halohydrin dehalogenase is a polypeptide comprising the amino acid sequence of SEQ ID NOs: 1, 2, 3 or 4.
5. The process of claim 1 , further comprising reacting the epoxide of formula (1) with the nucleophilic agent Nu in the presence of halohydrin dehalogenase at a temperature of 0° C. and 60° C.
6. The process of claim 2 , further comprising reacting the epoxide of formula (1) with the nucleophilic agent Nu in the presence of halohydrin dehalogenase at a temperature of 0° C. and 60° C.
7. The process of claim 1 , further comprising separating the optically enriched tertiary alcohol (2a) or (2b) from the epoxide (3a) or (3b) by crystallization.
8. The process of claim 2 , further comprising separating the optically enriched tertiary alcohol (2a) or (2b) from the epoxide (3a) or (3b) by crystallization.
9. The process of claim 1 , further comprising a subsequent step comprising reacting at least one of the epoxides (3a) or (3b) with a nucleophilic agent to the corresponding alcohol.
10. The process of claim 2 , further comprising a subsequent step comprising reacting at least one of the epoxides (3a) or (3b) with a nucleophilic agent to the corresponding alcohol.