Method for preparation of betulinic acid from betulin (SE 2011050818)

Jukka Tulisalo, Niko Wickholm, Minni Pirttimaa, Sami Alakurtti, Jari Yli-Kauhaluoma, Salme Koskimies

Forskningsoutput: PatentVetenskaplig

Sammanfattning

The present invention relates to a method for prepn. of betulinic acid (I) from betulin (II). The method comprises oxidizing betulin to betulinic and/or betulonic aldehyde with a ruthenium based catalyst, RumLmxn [L = ligand; m is 1, 2 or 3; n is 0, 1, 2, 3, 4, 5 or 6], catalyzed oxidn. process in the presence of an oxidant, and further converting the betulinic and/or betulonic aldehyde to betulinic acid. The method comprises oxidizing betulin to betulinic and/or betulonic aldehyde in the presence of a cocatalyst III [wherein each of R1 and R2 is independently H, alkyl, alkenyl, alkoxy, halogen, haloalkyl, OH, hydroxyalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, amino, imino, alkylamino, acylamino, NO2, CF3, OCF3, CO2H, carboxyalkyl, keto, thioxo, alkylthio, alkylsulfinyl, alkylsulfonyl, CN, carboxyl, AcNH, acetoxy, acetyl, benzamido, benzenesulfinyl, benzenesulfonamido, benzenesulfonyl, benzenesulfonylamino, benzoyl, benzoylamino, benzoyloxy, benzyl, benzyloxy, benzyloxycarbonyl,benzylthio, carbamoyl, carbamate, isocyanato, sulfamoyl, sulfinamoyl, sulfino, sulfo, sulfoamino, thiosulfo, NRxRy or COORx; ]. [Wherein each Rx and Ry are independently H, alkyl, alkenyl, aryl, heteroaryl, heterocycle, cycloalkyl or hydroxyl; wherein any alkyl group is optionally substituted on carbon with keto (:O); wherein any alkyl group is optionally interrupted with one or more nonperoxide, oxy (O), thio (S), imino (NH), methylenedioxy (OCH2O), carbonyl {C(:O)}, carboxy (CO2), carbonyldioxy (OCO2), carboxylato {OC(:O)}, imine (C:NH), sulfinyl (SO), sulfonyl (SO2) or [SiO]x, wherein X is about 1-10,000; or R1 and R2 together are thioxo (:S) or keto (:O)]. Thus, I was prepd. in two steps from II via oxidn. with RuCl2(PPh3)3 in PhMe in the presence of the co-catalyst TEMPO under O2; betulinic aldehyde thus formed was then oxidized with NaOCl2 in PhMe/t-BuOH contg. aq. NaH2PO4 and 2-methyl-2-butene. Alternatively, I was prepd. in three steps from II via oxidn. with TPAP in CH2Cl2 contg. NMO and 4Å mol. sieves to give betulonic aldehyde; oxidn. of the latter with NaOCl2 in PhMe/t-BuOH contg. aq. NaH2PO4 and 2-methyl-2-butene; and, redn. with NaBH4 in isopropanol contg. aq. NaOH.
Originalspråksvenska
Utgivningsår13 mar 2013
StatusPublicerad - 13 mar 2013
MoE-publikationstypH1 Beviljat patent

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Tulisalo, J., Wickholm, N., Pirttimaa, M., Alakurtti, S., Yli-Kauhaluoma, J., & Koskimies, S. (2013). Method for preparation of betulinic acid from betulin (SE 2011050818). (Patentnr. SE 2011050818).
Tulisalo, Jukka (Författare) ; Wickholm, Niko (Författare) ; Pirttimaa, Minni (Författare) ; Alakurtti, Sami (Författare) ; Yli-Kauhaluoma, Jari (Författare) ; Koskimies, Salme (Författare). / Method for preparation of betulinic acid from betulin (SE 2011050818). Patentnr.: SE 2011050818. mar 13, 2013.
@misc{aabb9d3c2c344954964c2f1ab8df385d,
title = "Method for preparation of betulinic acid from betulin (SE 2011050818)",
abstract = "The present invention relates to a method for prepn. of betulinic acid (I) from betulin (II). The method comprises oxidizing betulin to betulinic and/or betulonic aldehyde with a ruthenium based catalyst, RumLmxn [L = ligand; m is 1, 2 or 3; n is 0, 1, 2, 3, 4, 5 or 6], catalyzed oxidn. process in the presence of an oxidant, and further converting the betulinic and/or betulonic aldehyde to betulinic acid. The method comprises oxidizing betulin to betulinic and/or betulonic aldehyde in the presence of a cocatalyst III [wherein each of R1 and R2 is independently H, alkyl, alkenyl, alkoxy, halogen, haloalkyl, OH, hydroxyalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, amino, imino, alkylamino, acylamino, NO2, CF3, OCF3, CO2H, carboxyalkyl, keto, thioxo, alkylthio, alkylsulfinyl, alkylsulfonyl, CN, carboxyl, AcNH, acetoxy, acetyl, benzamido, benzenesulfinyl, benzenesulfonamido, benzenesulfonyl, benzenesulfonylamino, benzoyl, benzoylamino, benzoyloxy, benzyl, benzyloxy, benzyloxycarbonyl,benzylthio, carbamoyl, carbamate, isocyanato, sulfamoyl, sulfinamoyl, sulfino, sulfo, sulfoamino, thiosulfo, NRxRy or COORx; ]. [Wherein each Rx and Ry are independently H, alkyl, alkenyl, aryl, heteroaryl, heterocycle, cycloalkyl or hydroxyl; wherein any alkyl group is optionally substituted on carbon with keto (:O); wherein any alkyl group is optionally interrupted with one or more nonperoxide, oxy (O), thio (S), imino (NH), methylenedioxy (OCH2O), carbonyl {C(:O)}, carboxy (CO2), carbonyldioxy (OCO2), carboxylato {OC(:O)}, imine (C:NH), sulfinyl (SO), sulfonyl (SO2) or [SiO]x, wherein X is about 1-10,000; or R1 and R2 together are thioxo (:S) or keto (:O)]. Thus, I was prepd. in two steps from II via oxidn. with RuCl2(PPh3)3 in PhMe in the presence of the co-catalyst TEMPO under O2; betulinic aldehyde thus formed was then oxidized with NaOCl2 in PhMe/t-BuOH contg. aq. NaH2PO4 and 2-methyl-2-butene. Alternatively, I was prepd. in three steps from II via oxidn. with TPAP in CH2Cl2 contg. NMO and 4{\AA} mol. sieves to give betulonic aldehyde; oxidn. of the latter with NaOCl2 in PhMe/t-BuOH contg. aq. NaH2PO4 and 2-methyl-2-butene; and, redn. with NaBH4 in isopropanol contg. aq. NaOH.",
author = "Jukka Tulisalo and Niko Wickholm and Minni Pirttimaa and Sami Alakurtti and Jari Yli-Kauhaluoma and Salme Koskimies",
year = "2013",
month = "3",
day = "13",
language = "svenska",
type = "Patent",
note = "SE 2011050818",

}

Tulisalo, J, Wickholm, N, Pirttimaa, M, Alakurtti, S, Yli-Kauhaluoma, J & Koskimies, S mar. 13 2013, Method for preparation of betulinic acid from betulin (SE 2011050818), Patentnr. SE 2011050818.

Method for preparation of betulinic acid from betulin (SE 2011050818). / Tulisalo, Jukka; Wickholm, Niko; Pirttimaa, Minni; Alakurtti, Sami; Yli-Kauhaluoma, Jari; Koskimies, Salme.

Patentnr.: SE 2011050818. mar 13, 2013.

Forskningsoutput: PatentVetenskaplig

TY - PAT

T1 - Method for preparation of betulinic acid from betulin (SE 2011050818)

AU - Tulisalo, Jukka

AU - Wickholm, Niko

AU - Pirttimaa, Minni

AU - Alakurtti, Sami

AU - Yli-Kauhaluoma, Jari

AU - Koskimies, Salme

PY - 2013/3/13

Y1 - 2013/3/13

N2 - The present invention relates to a method for prepn. of betulinic acid (I) from betulin (II). The method comprises oxidizing betulin to betulinic and/or betulonic aldehyde with a ruthenium based catalyst, RumLmxn [L = ligand; m is 1, 2 or 3; n is 0, 1, 2, 3, 4, 5 or 6], catalyzed oxidn. process in the presence of an oxidant, and further converting the betulinic and/or betulonic aldehyde to betulinic acid. The method comprises oxidizing betulin to betulinic and/or betulonic aldehyde in the presence of a cocatalyst III [wherein each of R1 and R2 is independently H, alkyl, alkenyl, alkoxy, halogen, haloalkyl, OH, hydroxyalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, amino, imino, alkylamino, acylamino, NO2, CF3, OCF3, CO2H, carboxyalkyl, keto, thioxo, alkylthio, alkylsulfinyl, alkylsulfonyl, CN, carboxyl, AcNH, acetoxy, acetyl, benzamido, benzenesulfinyl, benzenesulfonamido, benzenesulfonyl, benzenesulfonylamino, benzoyl, benzoylamino, benzoyloxy, benzyl, benzyloxy, benzyloxycarbonyl,benzylthio, carbamoyl, carbamate, isocyanato, sulfamoyl, sulfinamoyl, sulfino, sulfo, sulfoamino, thiosulfo, NRxRy or COORx; ]. [Wherein each Rx and Ry are independently H, alkyl, alkenyl, aryl, heteroaryl, heterocycle, cycloalkyl or hydroxyl; wherein any alkyl group is optionally substituted on carbon with keto (:O); wherein any alkyl group is optionally interrupted with one or more nonperoxide, oxy (O), thio (S), imino (NH), methylenedioxy (OCH2O), carbonyl {C(:O)}, carboxy (CO2), carbonyldioxy (OCO2), carboxylato {OC(:O)}, imine (C:NH), sulfinyl (SO), sulfonyl (SO2) or [SiO]x, wherein X is about 1-10,000; or R1 and R2 together are thioxo (:S) or keto (:O)]. Thus, I was prepd. in two steps from II via oxidn. with RuCl2(PPh3)3 in PhMe in the presence of the co-catalyst TEMPO under O2; betulinic aldehyde thus formed was then oxidized with NaOCl2 in PhMe/t-BuOH contg. aq. NaH2PO4 and 2-methyl-2-butene. Alternatively, I was prepd. in three steps from II via oxidn. with TPAP in CH2Cl2 contg. NMO and 4Å mol. sieves to give betulonic aldehyde; oxidn. of the latter with NaOCl2 in PhMe/t-BuOH contg. aq. NaH2PO4 and 2-methyl-2-butene; and, redn. with NaBH4 in isopropanol contg. aq. NaOH.

AB - The present invention relates to a method for prepn. of betulinic acid (I) from betulin (II). The method comprises oxidizing betulin to betulinic and/or betulonic aldehyde with a ruthenium based catalyst, RumLmxn [L = ligand; m is 1, 2 or 3; n is 0, 1, 2, 3, 4, 5 or 6], catalyzed oxidn. process in the presence of an oxidant, and further converting the betulinic and/or betulonic aldehyde to betulinic acid. The method comprises oxidizing betulin to betulinic and/or betulonic aldehyde in the presence of a cocatalyst III [wherein each of R1 and R2 is independently H, alkyl, alkenyl, alkoxy, halogen, haloalkyl, OH, hydroxyalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, amino, imino, alkylamino, acylamino, NO2, CF3, OCF3, CO2H, carboxyalkyl, keto, thioxo, alkylthio, alkylsulfinyl, alkylsulfonyl, CN, carboxyl, AcNH, acetoxy, acetyl, benzamido, benzenesulfinyl, benzenesulfonamido, benzenesulfonyl, benzenesulfonylamino, benzoyl, benzoylamino, benzoyloxy, benzyl, benzyloxy, benzyloxycarbonyl,benzylthio, carbamoyl, carbamate, isocyanato, sulfamoyl, sulfinamoyl, sulfino, sulfo, sulfoamino, thiosulfo, NRxRy or COORx; ]. [Wherein each Rx and Ry are independently H, alkyl, alkenyl, aryl, heteroaryl, heterocycle, cycloalkyl or hydroxyl; wherein any alkyl group is optionally substituted on carbon with keto (:O); wherein any alkyl group is optionally interrupted with one or more nonperoxide, oxy (O), thio (S), imino (NH), methylenedioxy (OCH2O), carbonyl {C(:O)}, carboxy (CO2), carbonyldioxy (OCO2), carboxylato {OC(:O)}, imine (C:NH), sulfinyl (SO), sulfonyl (SO2) or [SiO]x, wherein X is about 1-10,000; or R1 and R2 together are thioxo (:S) or keto (:O)]. Thus, I was prepd. in two steps from II via oxidn. with RuCl2(PPh3)3 in PhMe in the presence of the co-catalyst TEMPO under O2; betulinic aldehyde thus formed was then oxidized with NaOCl2 in PhMe/t-BuOH contg. aq. NaH2PO4 and 2-methyl-2-butene. Alternatively, I was prepd. in three steps from II via oxidn. with TPAP in CH2Cl2 contg. NMO and 4Å mol. sieves to give betulonic aldehyde; oxidn. of the latter with NaOCl2 in PhMe/t-BuOH contg. aq. NaH2PO4 and 2-methyl-2-butene; and, redn. with NaBH4 in isopropanol contg. aq. NaOH.

M3 - Patent

M1 - SE 2011050818

Y2 - 2013/03/13

ER -

Tulisalo J, Wickholm N, Pirttimaa M, Alakurtti S, Yli-Kauhaluoma J, Koskimies S. Method for preparation of betulinic acid from betulin (SE 2011050818). SE 2011050818. 2013 mar 13.