Processing for preparing monoprotected diols from symmetric diols
View Patent ↗This invention provides a two-step enzymatic process for the synthesis of monoprotected diols from symmetric diols.
1. A process for producing a compound of the formula:
wherein n=1–5
which comprises
(a) mixing a compound of the formula:
with an effective amount of a first lipase which acts on anacyl donor, an acyl donor, and an optional organic solvent to yield a crude mixture of monoacetate and diacetate of the formulas:
(b) suspending the crude mixture in a buffer with a second lipase which acts on the acyl acceptor to yield an extractable monoacetate and diacetate of formulas (I) and (III); and
(c) purifying the extracted monoacetate to a compound of formula (I) having a purity of at least 98% and a yeild of at least 50%.
2. The process of claim 1 wherein the temperature in step (a) is about 20° C. to about 70° C.
3. The process of claim 1 wherein the temperature in step (a) is about 30° C. to about 55° C.
4. The process of claim 1 wherein the temperature in step (a) is about 40° C.
5. The process of claim 1 wherein the time in step (a) is about 3 hours to about 15 hours.
6. The process of claim 1 wherein the time in step (a) is about 5 hours to about 10 hours.
7. The process of claim 1 wherein the time in step (a) is about 8 hours.
8. The process of claim 1 wherein the organic solvent comprises tetrahydrofuran, ethyl acetate, acetonitrile, toluene, hexane, ethyl ether, tert-butylmethyl ether (TBME).
9. The process of claim 1 wherein the acyl donor is isopropenyl acetate.
10. The process of claim 1 wherein the acyl donor is vinyl acetate.
11. The process of claim 1 wherein the first lipase is a hydrolytic enzyme acting on an acyl donor.
12. The process of claim 1 wherein the second lipase is a hydrolytic enzyme acting on an acyl acceptor.
13. The process of claim 1 wherein the temperature of step (b) is about 20° C. to about 55° C.
14. The process of claim 1 wherein the temperature of step (b) is about 24° C.
15. The process of claim 1 wherein the time of step (b) about 4 hours to about 12 hours.
16. The process of claim 1 wherein the time is about 5 hours to about 10 hours.
17. The process of claim 1 wherein the time is about 8 hours.
18. The process of claim 1 wherein the pH is about 5.0 to about 8.5.
19. The process of claim 1 wherein the pH is about 6.8 to about 6.85.
20. The process of claim 1 wherein the compound of formula (I) is 4-hydroxy2-butynyl acetate.