PROCESS FOR THE SYNTHESIS OF ALPHA-METHYLENE-GAMMA-BUTYROLACTONE
Abstract:
The present application provides a process for the preparation of α-methylene-γ-butyrolactone, said process comprising the steps of: a) acetylating the C1-hydroxyl group of isoprenol to yield isoprenyl acetate; b) forming 4-acetoxy-2-methylene-butan-1-ol from said isoprenyl acetate by whole cell biotransformation, said step comprising: i) contacting a cell (CB) with a culture medium containing said isoprenyl acetate or with a culture medium contiguous with an organic phase containing said isoprenyl acetate under conditions that enable the cell to form 4-acetoxy-2-methylene-butan-1-ol from isoprenyl acetate; and, ii) optionally isolating the resultant 4-acetoxy-2-methylene-butan-1-ol, wherein said cell (CB) exhibits activity of at least one alkane monooxygenase enzyme which catalyzes the formation of 4-acetoxy-2-methylene-butan-1-ol from isoprenyl acetate; c) oxidizing said 4-acetoxy-2-methylene-butan-1-ol to yield 4-acetoxy-2-methylene butyric acid; and, d) converting said 4-acetoxy-2-methylene butyric acid to α-methylene-γ-butyrolactone by hydroxylysis to γ-hydroxy-α-methylenebutyric acid and subsequent cyclization of said γ-hydroxy-α-methylenebutyric acid.
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