Method for preparing phosphorylated keto polyols, derivatives thereof and uses thereof

A method for preparing a phosphorylated keto polyol of formula (I)

• or a cyclic hemiketal isomer thereof,
• comprising a step of reacting dihydroxyacetone phosphate (DHAP) with a ketone of formula (III) selected from a 1,2-diketone and a ketone having a substituent X at a position alpha of the carbonyl group:
• in the presence of a class II DHAP aldolase,
• wherein R1 and R2 are such that:
• the molecular weight of the ketone of formula (III) is less than 600 g·mol−1,
• neither R1 nor R2 are H, and
• the carbonyl group shown in formula (III) is included in a moiety selected from:
• wherein X is selected from the group consisting of
• OH, F, Cl, Br, I, —N3, cyano, nitro, —COOH, —SO3H, —C(F)3, —C(Cl)3, —C(Br)3, —C(I)3,
• —NHC(═O)R, —NHC(═O)OR, —OR, —SR, —SO2R, —C(═O)R, —C(═O)OR, —C(═O)NHR, —OC(═O)OR, —C(═O)SR, wherein R is a substituted or unsubstituted C1-C10 alkyl, a substituted or unsubstituted C5-C10 aryl or a substituted or unsubstituted C4-C10 heteroaryl group,
• —N(R3)3+ wherein each R3 is independently selected from H, C1-C10 alkyl and C5-C10 aryl,
• OP(═O)(R4)2 and P(═O)(R4)2 wherein each R4 is independently selected from H, a substituted or unsubstituted C1-C10 alkyl, a substituted or unsubstituted C5-C10 aryl, a substituted or unsubstituted C4-C10 heteroaryl group, substituted or unsubstituted C1-C10 alkoxy and substituted or unsubstituted C5-C10 aryloxy.

A compound selected from:

• a phosphorylated keto polyol of formula (I)
• and
• a keto polyol of formula (II)
• wherein R1 and R2 are such that
• the compound comprises a moiety selected from:
• wherein X is selected from the group consisting of —OH, —OCH3, and a halogen, and
• R1 and R2 are independently selected from the group consisting of —(CH2)p-Ph, —OH, —CH2—C(═O)—R, —COOH, —C(═O)—R, unsubstituted C1-C3 alkyl, C1-C3 alkyl substituted with at least one group selected from —OH, —OCH3, and a halogen;
• wherein Ph is a phenyl, p is 1 or 2, and R is a C1-C3 alkyl;
• or
• R1 and R2 form together, with the carbon bearing the tertiary alcohol function, a C6 ring bearing at least one group selected from —OH, —OCH3, and a halogen at position alpha of the carbonyl group or bearing a second carbonyl group at position alpha or beta of the carbonyl group,
• a salt thereof, and
• a cyclic hemiketal isomer thereof,
• with proviso that said compound is not the compound (1b) or (2b) as shown in table 4, or a cyclic hemiketal isomer or salt thereof.

A method for promoting the reaction of dihydroxyacetone phosphate (DHAP) with a ketone selected from a 1,2-diketone and a ketone having, at a position alpha of the carbonyl group, a substituent selected from the group consisting of:

• OH, F, Cl, Br, I, azido, cyano, nitro, —COOH, —SO3H, —C(F)3, —C(Cl)3, —C(Br)3, —C(I)3,
• —NHC(═O)R, —NHC(═O)OR, —OR, —SR, —SO2R, —C(═O)R, —C(═O)NHR, —OC(═O)OR, —C(═O)OR, —C(═O)SR, wherein R is a substituted or unsubstituted C1-C10 alkyl, a substituted or unsubstituted C5-C10 aryl or a substituted or unsubstituted C4-C10 heteroaryl group,
• —N(R3)3+ wherein each R3 is independently selected from H, C1-C10 alkyl and C5-C10 aryl,
• OP(═O)(R4)2 and P(═O)(R4)2 wherein each R4 is independently selected from H, a substituted or unsubstituted C1-C10 alkyl, a substituted or unsubstituted C5-C10 aryl, a substituted or unsubstituted C4-C10 heteroaryl group, substituted or unsubstituted C1-C10 alkoxy and substituted or unsubstituted C5-C10 aryloxy,
• which comprises a step of reacting DHAP with the ketone in the presence of a class II DHAP aldolase selected from an enzyme having a RhaD activity, a FucA activity or a TagA activity.