Science of Synthesis

de Gonzalo, G.; van Berkel, W. J. H.; Fraaije, M. W., Science of Synthesis: Biocatalysis in Organic Synthesis, (2015) 3, 225.

3-Alkyl-3,4-dihydro-1H-2-benzopyran-1-ones ‌82‌ are valuable compounds that can be prepared from the corresponding 2-alkyl-2,3-dihydro-1H-inden-1-ones under mild reaction conditions using the purified Met446Gly mutant of phenylacetone monooxygenase (M446G PAMO) and the secondary enzymatic system glucose 6-phosphate/glucose 6-phosphate dehydrogenase (G6PDH) for NADPH regeneration.[‌82‌] These ketones can be easily racemized by using a high pH, while the biocatalyst regioselectively affords the abnormal lactones ‌82‌ (‌Scheme 29‌). Process optimization shows that the best results are achieved when using the biocatalyst at pH 10.0 and 40 °C, while the presence of 5% hexane as an organic cosolvent has a positive effect on the enzyme selectivity for some of the substrates. Oxidations are performed at a 50-mg scale under these conditions, obtaining the final optically active 3-alkyl-3,4-dihydro-1H-2-benzopyran-1-ones ‌82‌ with good yields and high optical purities. The oxidation of racemic 2-methyl-2,3-dihydro-1H-inden-1-one has also been performed on a larger scale by employing a cell-free extract preparation of M446G PAMO.

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References