Process for Manufacture of Optically Active 2-(Acyloxymethyl)-1,3-Oxathiolanes
AssigneeThesis Chemistry, LLC
InventorJohn R. Peterson
Life of this patent
Estimating the term…
Abstract
There is provided a process for manufacture of optically-active, 2-(acyloxymethyl)-1,3-oxathiolanes of Formula I comprising a preparation of a racemic compound and an enzyme-catalyzed kinetic resolution of the enantiomers. The invention may further provide for the esterification and racemization of the by-product of the enzymatic reaction. In this manner, 2(R)-(benzoyloxymethyl)-1,3-oxathiolane is prepared as a useful intermediate for manufacture of the anti-HIV drug Apricitabine.
Claims31
A method for enzymatic kinetic resolution of 2-(acyloxymethyl)-1,3-oxathiolanes of Formula I
- comprising the steps of:
- (i) exposing a compound of Formula I to a hydrolytic enzyme and (ii) allowing said enzyme to catalyze an enzymatic reaction wherein said reaction preferentially forms an enantiomer of Formula I where R1 is a group selected from among hydrogen, alkyl, alkenyl, alkynyl, aralkyl, aryl, cycloalkenyl, cycloalkenyl-alkyl, cycloalkyl, cycloalkyl-alkyl, heteroaryl, heteroaryl-alkyl, heterocycloalkyl, or heterocycloalkyl-alkyl.
A process for esterification and racemization of a 2(S)-(hydroxymethyl)-1,3-oxathiolane compound of Formula IIIa;
- or a 2(R)-(hydroxymethyl)-1,3-oxathiolane compound of Formula IIIb;
- comprising the steps of:
- (i) an esterification reaction of said compound of Formula IIIa or said compound of Formula IIIb with an esterification agent, so as to generate a 2(S)-(acyloxymethyl)-1,3-oxathiolane compound of Formula Ib
- or a 2(R)-(acyloxymethyl)-1,3-oxathiolane compound of Formula Ia
- where R1 is a group selected from among hydrogen, or alkyl, or alkenyl, or alkynyl, or aralkyl, or aryl, or cycloalkenyl, or cycloalkenyl-alkyl, or cycloalkyl, or cycloalkyl-alkyl, or heteroaryl, or heteroaryl-alkyl, or heterocycloalkyl, or heterocycloalkyl-alkyl, and
- (ii) an acid-mediated racemization of said compound of Formula Ia or said compound of Formula Ib yielding a compound of Formula I of lower enantiomeric enrichment than said compound of Formula Ia or said compound of Formula Ib.
Dependencies are inferred from the claim text.