The present application relates to enantioselective enzymatic reduction of keto compounds to the corresponding chiral hydroxy compounds. Specifically the present application describes enantioselective enzymatic reduction of ethyl-4-chloroacetoacetate (compound of formula I) into (R)-ethyl-4-chloro-3-hydroxybutyrate (compound of formula II). The present application also covers use of (R)-ethyl-4-chloro-3-hydroxybutyrate prepared by the enantioselective enzymatic reduction process in the preparation of SGLT2 inhibitor empaglifiozin.

##STR00001##

The invention relates to the field of pharmaceutical synthesis, in particular to the preparation method of hexahydrofuro-furanol derivative, intermediates thereof and preparation methods thereof. The preparation methods comprises the steps of halogenation reaction, acylation reaction, enzymatic reduction reaction, reaction with amine compounds, reduction ring closure reaction (A1, A2, B, Cp1, C.sub.L, Cf)

##STR00001##

wherein, R.sub.1, R.sub.2, R.sub.3 are hydrogen or hydroxy protecting groups; R.sub.4 and R.sub.5 are the same or different and are phenyl, alkyl or substituted phenyl. In the preparation process of hexahydrofuro-furanol derivatives, the chirality is constructed by enzymatic method, and the product can be prepared with very high optical purity by adopting such technical means. The preparation method can be used to prepare the key intermediate, (3R, 3aS, 6aR)-hexahydrofuro[2,3-b]-3-ol, of Darunavir, in commercial production, which is a very economical route suitable for industrial production.

The invention relates to the field of pharmaceutical synthesis, in particular to the preparation method of hexahydrofuro-furanol derivative, intermediates thereof and preparation methods thereof. The preparation methods comprises the steps of halogenation reaction, acylation reaction, enzymatic reduction reaction, reaction with amine compounds, reduction ring closure reaction (A1, A2, B, Cp1, C.sub.L, Cf)

##STR00001##

wherein, R.sub.1, R.sub.2, R.sub.3 are hydrogen or hydroxy protecting groups; R.sub.4 and R.sub.5 are the same or different and are phenyl, alkyl or substituted phenyl. In the preparation process of hexahydrofuro-furanol derivatives, the chirality is constructed by enzymatic method, and the product can be prepared with very high optical purity by adopting such technical means. The preparation method can be used to prepare the key intermediate, (3R, 3aS, 6aR)-hexahydrofuro[2,3-b]-3-ol, of Darunavir, in commercial production, which is a very economical route suitable for industrial production.

Provided herein are methods for making gamma lactones comprising reacting a carboxylic acid substrate with a heterologous cytochrome P450 (CYP450) protein with carboxylic acid 4-hydroxylase activity.

Provided herein are methods for making gamma lactones comprising reacting a carboxylic acid substrate with a heterologous cytochrome P450 (CYP450) protein with carboxylic acid 4-hydroxylase activity.

The present disclosure relates to a transformant for producing 2,5-furandicarboxylic acid. The transformant for producing 2,5-furandicarboxylic acid includes a Pseudomonas putida and at least one exogenous gene. The exogenous gene is an HmfH gene or an HMFO gene, and the exogenous gene is integrated into the chromosome of the Pseudomonas putida.

The present disclosure relates to a transformant for producing 2,5-furandicarboxylic acid. The transformant for producing 2,5-furandicarboxylic acid includes a Pseudomonas putida and at least one exogenous gene. The exogenous gene is an HmfH gene or an HMFO gene, and the exogenous gene is integrated into the chromosome of the Pseudomonas putida.

The present disclosure relates to processes that combine microbial production of organic intermediates and subsequent synthetic transformation to provide compounds of industrial value, including compounds used in fragrances.

The present disclosure relates to processes that combine microbial production of organic intermediates and subsequent synthetic transformation to provide compounds of industrial value, including compounds used in fragrances.

There is provided SHC/HAC derivatives, amino acid sequences comprising the SHC/HAC derivatives, nucleotide sequences encoding the SHC/HAC derivatives, vectors comprising nucleotide sequences encoding the SHC/HAC derivatives, recombinant host cells comprising nucleotide sequences encoding the SHC/HAC derivatives and applications of the recombinant host cells comprising either SHC/HAC derivatives or WT SHC/HAC enzymes in methods to prepare (−)-Ambrox and SHC/HAC enzymes in methods to prepare (−)-Ambrox.