Preparation of Betulinic Acid Derivatives in Organic Solvents

• Main Author: Issak, Anishah
• Format: Thesis
• Language: English; English
• Published: 2004
• Online Access: http://psasir.upm.edu.my/id/eprint/383/1/549696_FSAS_2004_41.pdf; http://psasir.upm.edu.my/id/eprint/383/

Betulinic acid has been identified as a potential natural product in medical field. The objectives of this research were to discover a new method for the modification of betulinic acid’s functional groups (C-3 and C-28 position) and to evaluate its activity against cancer cell. Modification at C-3 position was firstly carried out using acetate anhydride/pyridine with chemical reaction of 79% yield and was successfully modified using enzymatic reaction using Novozyme 435 in 85% yield. The later reaction is a new method for the preparation of 3β-acetoxy-lup20(29)-ene-28-oic acid using enzymatic reaction. Further modification at C- 28 position was carried out through an enzymatic reaction to produce betulinic acetate ester (3β-acetoxy-lup20(29)-ene-28-decanoate). Immobilized lipase from Candida antartica and Mucor miehei (Novozyme 435 and Lipozyme) were used. Novozyme 435 gave better esterification product of 3β-acetoxy-lup20(29)-ene-28-decanoate. To our knowledge, the esterification of 3β-acetoxy-lup20(29)-ene-28-decanoate using enzymatic reaction has not been reported previously. The effect of various parameters such as reaction time (1-24 h), initial water activity aw (0.11 - 0.90), substrate molar ratio of 1-decanol to 3β-axetoxy-lup20(29)-ene-28-oic acid (1:1 to 1:30) and various organic solvents on the esterification reaction was studied. Novozyme 435 was observed performed well in this study and gave maximum percent conversions of esterification under the following condition: reaction time (24 h), initial water activity aw (0.33), substrate molar ratio (1:15) in chloroform. These betulinic acid derivatives were then evaluated for their inhibitory activity against human leukemia cell line (HL60). Our results suggested that betulinic acid derivatives reduce their cytotoxicity compared with betulinic acid itself.