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

Patent metadata

Field	Value
Publication number	US-2020208181-A1
Application number	US-201816615427-A
Country	US
Kind code	A1
Filing date	May 22, 2018
Priority date	May 23, 2017
Publication date	Jul 2, 2020
Grant date	—

Abstract

The present invention relates to a method for preparing phosphorylated keto polyols by biocatalysis and uses thereof.

First claim

1 - 18 . (canceled)

19 . 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 R 1 and R 2 are such that:
the molecular weight of the ketone of formula (III) is less than 600 g·mol −1 ,
neither R 1 nor R 2 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, —N 3 , cyano, nitro, —COOH, —SO 3 H, —C(F) 3 , —C(Cl) 3 , —C(Br) 3 , —C(I) 3 ,
—NHC(═O)R, —NHC(═O)OR, —OR, —SR, —SO 2 R, —C(═O)R, —C(═O)OR, —C(═O)NHR, —OC(═O)OR, —C(═O)SR, wherein R is a substituted or unsubstituted C 1 -C 10 alkyl, a substituted or unsubstituted C 5 -C 10 aryl or a substituted or unsubstituted C 4 -C 10 heteroaryl group,
—N(R 3 ) 3 + wherein each R 3 is independently selected from H, C 1 -C 10 alkyl and C 5 -C 10 aryl,
OP(═O)(R 4 ) 2 and P(═O)(R 4 ) 2 wherein each R 4 is independently selected from H, a substituted or unsubstituted C 1 -C 10 alkyl, a substituted or unsubstituted C 5 -C 10 aryl, a substituted or unsubstituted C 4 -C 10 heteroaryl group, substituted or unsubstituted C 1 -C 10 alkoxy and substituted or unsubstituted C 5 -C 10 aryloxy.

20 . The method of claim 19 , wherein the ketone of formula (III) is characterized in that:
R 1 and R 2 are independently selected from the group consisting of —(CH 2 ) p -Ph, —COOH, —C(═O)—R, —CH 2 —C(═O)—R, —C(═O)OR, and C 1 -C 10 , optionally substituted with at least one group selected from —OH, C 1 -C 3 alkoxy, C 1 -C 3 alkyl, —F, —Cl, —Br, —I, wherein:
Ph is a phenyl optionally substituted by one or several substituents selected from halogens, —OH, C 1 -C 6 alkyl, and C 1 -C 6 alkoxy,
p is an integer from 1 to 6, and
R is a C 1 -C 6 alkyl optionally substituted by one or several substituents selected from halogens, —OH, C 1 -C 3 alkyl, and C 1 -C 3 alkoxy, or
R 1 and R 2 form together, with the carbonyl group, a C 5 -C 6 ring bearing at least one group selected from —OH, —OCH 3 , —F, —Cl, —Br, —I, at position alpha of the carbonyl group or a second oxo group at position alpha or beta of the carbonyl group.

21 . The method of claim 19 , wherein the ketone of formula (III) is such that:
R 1 and R 2 are independently selected from the group consisting of —(CH 2 ) p -Ph, wherein Ph is a phenyl, and p is 1 or 2; COOH; —CH 2 —C(═O)—R, —C(═O)—R wherein R is a C 1 -C 3 alkyl; C 1 -C 6 alkyl optionally substituted with at least one group selected from —OH, —OCH 3 and —Cl, or R 1 and R 2 form together, with the carbonyl group, a C 6 ring bearing at least one group selected from —OH, —OCH 3 , and —Cl at position alpha of the carbonyl group or bearing a second oxo group at position alpha or beta of the carbonyl group.

22 . The method of claim 19 , wherein the ketone of formula (III) is selected from ketones of formula (IIIa):

wherein X is selected from the group consisting of:
OH, F, Cl, Br, I, —N 3 , cyano, nitro, —COOH, —SO 3 H, —C(F) 3 , —C(Cl) 3 , —C(Br) 3 , —C(I) 3 , —NHC(═O)R, —NHC(═O)OR, —OR, —SR, —SO 2 R, —C(═O)R, —C(═O)OR, C(═O)NHR, —OC(═O)OR, —C(═O)SR, wherein R is a substituted or unsubstituted C 1 -C 10 alkyl, a substituted or unsubstituted C 5 -C 10 aryl or a substituted or unsubstituted C 4 -C 10 heteroaryl group,
—N(R 3 ) 3 + wherein each R 3 is independently selected from H, C 1 -C 10 alkyl and C 5 -C 10 aryl, and
OP(═O)(R 4 ) 2 and P(═O)(R 4 ) 2 wherein each R 4 is independently selected from H, a substituted or unsubstituted C 1 -C 10 alkyl, a substituted or unsubstituted C 5 -C 10 aryl, a substituted or unsubstituted C 4 -C 10 heteroaryl group, substituted or unsubstituted C 1 -C 10 alkoxy and substituted or unsubstituted C 5 -C 10 aryloxy,
P(═O)(R 4 ) 2 and P(═O)(R 4 ) 2 wherein each R 4 is independently selected from H, a substituted or unsubstituted C 1 -C 10 alkyl, a substituted or unsubstituted C 5 -C 10 aryl, a substituted or unsubstituted C 4 -C 10 heteroaryl group, substituted or unsubstituted C 1 -C 10 alkoxy and substituted or unsubstituted C 5 -C 10 aryloxy, R 1 and R 5 are such that:
R 1 and R 5 form together, with the moiety (a), a C 5 -C 6 ring optionally bearing at least one additional substituent, said additional substituent being selected from NH 2 , OH, F, Cl, Br, I, —N 3 , cyano, nitro, SH, —CONH 2 , —COOH, —SO 3 H, —C(F) 3 , C 1 -C 3 alkyl, C 1 -C 3 alkoxy, C 1 -C 3 alkylamino, C 1 -C 3 aminoalkyl, C 1 -C 3 N,N-dialkylamino alkyl, C 1 -C 3 N-alkylamino alkyl, OP(═O)(OH) 2 , —SO 3 H, C 1 -C 3 hydroxyalkyl, C 1 -C 3 haloalkyl, C 1 -C 3 alkylthio, and C 1 -C 3 thioalkyl,
or
R 1 and R 5 are independently selected from the group consisting of H, —OH, —(CH 2 ) p -Ph, unsubstituted C 1 -C 6 alkyl, and substituted C 1 -C 6 alkyl wherein:
R 1 is not H,
p is an integer from 1 to 6,
Ph is a phenyl group optionally substituted by one or several groups selected from NH 2 , OH, F, Cl, Br, I, —N 3 , cyano, nitro, SH, —CONH 2 , —COOH, —SO 3 H, —C(F) 3 , C 1 -C 3 alkyl, C 1 -C 3 alkoxy, C 1 -C 3 alkylamino, C 1 -C 3 aminoalkyl, C 1 -C 3 N,N-dialkylamino alkyl, C 1 -C 3 N-alkylamino alkyl, OP(═O)(OH) 2 , —SO 3 H, C 1 -C 3 hydroxyalkyl, C 1 -C 3 haloalkyl, C 1 -C 3 alkylthio, and C 1 -C 3 thioalkyl,
the substituted C 1 -C 6 alkyl comprises at least one substituent selected from NH 2 , OH, F, Cl, Br, I, —N 3 , cyano, nitro, SH, —CONH 2 , —COOH, —SO 3 H, —C(F) 3 , C 1 -C 3 alkyl, C 1 -C 3 alkoxy, C 1 -C 3 alkylamino, C 1 -C 3 aminoalkyl, C 1 -C 3 N,N-dialkylamino alkyl, C 1 -C 3 N-alkylamino alkyl, OP(═O)(OH) 2 , —SO 3 H, C 1 -C 3 hydroxyalkyl, C 1 -C 3 haloalkyl, C 1 -C 3 alkylthio, and C 1 -C 3 thioalkyl.

23 . The method of claim 22 , wherein:
X is selected from —OH, —OCH 3 , a halogen, and C(═O)CH 3 , R 1 and R 5 are independently selected from H, C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted by 1 to 6 substituents selected from C 1 -C 3 alkoxy, C 1 -C 3 haloalkyl, F, Cl, Br, I and OH; and —CH 2 -Ph optionally bearing at least one substituent selected from F, Cl, Br, I, —OH, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, and C 1 -C 3 alkoxy;
with proviso that R 1 is not H, or
R 1 and R 5 form together with the moiety (a), a C 5 -C 6 ring optionally bearing at least one additional substituent selected from —OH, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, F, Cl, Br, I and C 1 -C 3 alkoxy.

24 . The method of claim 19 , wherein ketone of formula (III) is selected from ketones of formula (IIIb):

wherein:
R 1 and R 6 are independently selected from the group consisting of —OH, C 1 -C 6 alkyloxy, —(CH 2 ) p -Ph, unsubstituted C 1 -C 6 alkyl, and substituted C 1 -C 6 alkyl wherein:
p is an integer from 1 to 6,
Ph is a phenyl group optionally substituted by one or several substituents selected from NH 2 , OH, F, Cl, Br, I, —N 3 , cyano, nitro, SH, —CONH 2 , —COOH, —SO 3 H, —C(F) 3 , C 1 -C 3 alkyl, C 1 -C 3 alkoxy,

Assignees

• Commissariat Energie Atomique
• Centre Nat Rech Scient
• Univ Clermont Auvergne
• Univ Devry Val Dessonne

Inventors

• De Berardinis Véronique
• Salanoubat Marcel
• Lemaire Marielle
• Guerard-Helaine Christine

Classifications

• C12Y401/0204

  Tagatose-bisphosphate aldolase (4.1.2.40) · CPC title

• C12Y401/02019

  Rhamnulose-1-phosphate aldolase (4.1.2.19) · CPC title

• C12Y401/02017

  L-Fuculose-phosphate aldolase (4.1.2.17) · CPC title

• C12Y401/00

  Carbon-carbon lyases (4.1) · CPC title

• C12P7/26

  Ketones · CPC title