Betulinic acid esters derivative and preparation method and use of betulinic acid esters derivative

A technology of betulinic acid esters and derivatives, applied in the direction of drug combinations, steroids, antineoplastic drugs, etc., to achieve the effect of improving anticancer activity

CN102924558AInactive Publication Date: 2013-02-13GUIZHOU UNIV
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Patent Information

Authority / Receiving Office
CN · China
Current Assignee / Owner
Publication Date
2013-02-13
Estimated Expiration
Not applicable · inactive patent

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Abstract

The invention discloses a betulinic acid esters derivative and a preparation method and use of the betulinic acid esters derivative. The compound structure of the betulinic acid esters derivative is shown as general formulae (I) and (II). The invention introduces the betulinic acid esters derivative synthesized through a substitution reaction and an acid amine condensation reaction by using betulinic acids, halogenated hydrocarbons, secondary amines, piperazine, aromatic acids and substituted aromatic acids as raw materials. The compounds can be used for preparing anti-cancer drugs. The formulae (I) and (II) are shown as the specification.
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Description

technical field

[0001] The invention relates to betulinic acid ester derivatives with anticancer effects and a preparation method thereof. Background technique

[0002] Betulinic acid (Betulinic Acid, 3 β -Hydroxy-20(29)-ene-lupine-28-acid) is a pentacyclic triterpenoid compound that was discovered earlier and has good biological activity. Betulinic acid and its derivatives have antitumor properties (Simone F. Betulinic Acid for Cancer Treatment and Prevention. Int. J. Mol. Sci., 2008, 9: 1096-1107; Gao Y.; Jia Z.; Kong X.; Li Q.; Chang D.Z.; Wei D.; Le X . Combining Betulinic Acid and Mithramycin A Effectively Suppresses Pancreatic Cancer by Inhibiting Proliferation, Invasion, and Angiogenesis [J]. Cancer Res., 2011, 71(15): 5182-5193), anti-HIV and other biological activities (Pinzarua S. C.; Leopolda N .; Kieferb W. Vibrational spectroscopy of betulinicacidHIV inhibitor and of its birch bark natural source [J]. Talanta, 2002, 57: 625–631; Lan P.; Chen W. N.; Sun P. H; C...

Examples

Embodiment 1

[0077] Embodiment 1, (2-bromoethyl) 3 β The preparation of -hydroxy-20(29)-alkene-lupin-28-ester (the compound number is a )

[0078] Add 1 g of betulinic acid and 60 mg of K 2 CO 3 , dissolved in 10 mL of DMF, added 1.6 g of 1,2-dibromoethane, and reacted at room temperature for 12 h. After stopping the reaction, disperse with 50 mL of water, and extract 3 times with ethyl acetate, 10 mL each time, to obtain the mother liquor which is successively washed with 1N HCl, saturated NaHCO 3 , after washing twice with saturated NaCl aqueous solution, the combined ethyl acetate layers were dried over anhydrous sodium sulfate, evaporated to remove the solvent, separated by silica gel column chromatography, and eluted with petroleum ether:ethyl acetate=20:1 to obtain the target product, The yield was 72.9%.

Embodiment 2

[0079] Embodiment two, (2-bromopropyl) 3 β- Preparation of hydroxy-20(29)-alkene-lupin-28-ester (the compound number is b )

[0080] Synthesized under the same conditions and method as in Example 1, except that 1.7 g of 1,3-dibromopropane was added.

Embodiment 3

[0081] Embodiment three, (2-bromobutyl) 3 β The preparation of -hydroxy-20(29)-alkene-lupin-28-ester (the compound number is c )

[0082] Synthesized under the same conditions and methods as in Example 1, except that 1.8 g of 1,4-dibromobutane was added.