Process for the preparation of optically active 2-[6-hydroxymethyl)-1,3-dioxan-4yl]acetic acid derivatives

A process for producing a compound of the following general formula (I):

• wherein R1 represents hydrogen, an alkyl group of 1 to 12 carbon atoms, an aryl group of 6 to 12 carbon atoms or an aralkyl group of 7 to 12 carbon atoms, R4 and R5 each independently represents hydrogen, an alkyl group of 1 to 12 carbon atoms, an aryl group of 6 to 12 carbon atoms or an aralkyl group of 7 to 12 carbon atoms, and R4 and R5 may be bound to each other to form a ring, which comprises
• (1) reacting an enolate prepared by permitting either a base or a metal having a valency of 0 to act on an acetic ester derivative of the following general formula (II)
• wherein R1 represents hydrogen, an alkyl group of 1 to 12 carbon atoms, an aryl group of 6 to 12 carbon atoms an aralkyl group of 7 to 12 carbon atoms, and X2 represents hydrogen or a halogen atom, with a compound of the following general formula (III):
• wherein R2 represents an alkyl group of 1 to 12 carbon atoms, an aryl group of 6 to 12 carbon atoms or an aralkyl group of 7 to 12 carbon atoms, and X2 represents a halogen atom, at a temperature of not less than −30° C. to give a compound of the following general formula (IV):
• wherein R1 and X1 are as defined above,
• (2) reducing this compound with the aid of a strain of microorganism to give a compound of the following general formula (V):
• wherein R1 and X1 are as defined above,
• (3) treating this compound with an acetalizing agent in the presence of an acid catalyst to give a compound of the following general formula (VI):
• wherein R1 and X1 are as defined above, R4 and R5 each independently represents hydrogen, an alkyl group of 1 to 12 carbon atoms, an aryl group of 6 to 12 carbon atoms or an aralkyl group of 7 to 12 carbon atoms, and R4 and R5 may be bound to each other to form a ring,
• (4) acyloxylating this compound with an acyloxylating agent to give a compound of the following general formula (VII):
• wherein R1, R4 and R5 are as defined above, R3 represents hydrogen, an alkyl group of 1 to 12 carbon atoms, an aryl group of 6 to 12 carbon atoms or an aralkyl group of 7 to 12 carbon atoms, and
• (5) subjecting this compound to solvolysis in the presence of a base, wherein the strain of microorganism used in the step (2) is selected from the group of genera of microorganisms consisting of Hormoascus, Candida, Cryptococcus, Debaryomyces, Geotrichum, Kuraishia, Hansenulla, Kluyveromyces, Pichia, Yamadazyma, Rhodotorula, Saccharomyces, Schizoblastosporon, Zygosaccharomyces, Brevibacterium, Corynebacterium, and Rhodococcus.