Betulinic acid (3β-hydroxy-20 (29) -lupaen-28-oic acid) is a natural pentacyclic triterpenoid. It is contained in the bark of some plant species, mainly fluffy birch (Betula pubescens), from which it got its name.
| Betulinic acid | |
|---|---|
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| Are common | |
| Systematic name | betulinic acid |
| Chem. formula | C 30 H 48 O 3 |
| Physical properties | |
| Molar mass | 456.70 g / mol |
| Thermal properties | |
| T. melt. | 316 - 318 ° C |
| T. decomp. | 295 - 298 ° C |
| Classification | |
| Reg. CAS number | |
| PubChem | |
| Reg. EINECS number | |
| Smiles | |
| Inchi | |
| Chebi | |
| ChemSpider | |
Content
Pharmacological activity
Betulinic acid and its derivatives have anti-inflammatory, antitumor and anti-HIV activity. [1] [2]
Getting
There are a number of methods for producing betulinic acid from betulin , which can be divided into two groups. The first group of methods includes multistage schemes that allow avoiding changes in the spatial orientation of the hydroxyl group at position 3 and obtain a biologically active 3β-isomer. The essence of these methods is to protect the hydroxyl groups of betulin, deprotect the primary hydroxyl group, oxidize the primary hydroxyl group to a carboxyl group, and deprotect the secondary hydroxyl group.
A five-stage method was developed for producing betulinic acid from betulin, in which, in the first stage, the primary hydroxyl group is protected by dihydropyran with the formation of betulin tetrahydropyran ether. Then, the secondary hydroxyl group is protected by acylation with acetic anhydride in pyridine, followed by removal of the tetrahydropyran protection. Then, betulin monoacetate is oxidized with Jones reagent to betulinic acid monoacetate, followed by obtaining betulinic acid by cleavage of the acetyl group by potassium carbonate in methanol. This method makes it possible to obtain the 3β-isomer of betulinic acid, which, in contrast to the 3α-isomer, has biological activity. The disadvantages of this method include its multi-stage nature, and, consequently, the duration of the process as a whole and the small total yield of the target product (40-50%). [3]
The second group of methods is represented by two-stage schemes, allowing to achieve the desired result in a shorter way, but with the conversion of a small amount of the target product (about 15%) into biologically inactive 3α-hydroxy-20 (29) -lupaen-28-oic acid (3α-isomer. The advantages of this group of methods are associated not only with a reduction in the number of process steps, but also with an increase in the yield of the target product, even taking into account a decrease in the yield of the 3β-isomer due to the appearance of the 3α-isomer. e is oxidized to betulonic acid, which is then reduced with aluminum isopropylate or complex hydrides to betulinic acid. [4]
Notes
- ↑ Pisha E. Method for selectivity inhibiting melanoma, using betulinic acid. Nat. Med. 1995. Vol. 1. P. 1046-1051
- ↑ Fujioka T. Compounds and methods of use to treat HIV infections. J. Nat. Prod. 1994. Vol. 57. P. 243 - 247.
- ↑ Pezzuto Dg., Darrick SHL Kim. Methods of manufacturing betulinic acid. US patent 5.804.575.1997.
- ↑ Ruzicka L., Lamberton AH, Christe Ruzicka CW Synthetic approach to betulinic acid. Helv. Chim. Acta. 1938. Vol. 21. P. 1706-1717.
Literature
- Pisha E. Method for selectivity inhibiting melanoma, using betulinic acid. Nat. Med. 1995. Vol. 1. P. 1046-1051.
- Fujioka T. Compounds and methods of use to treat HIV infections. J. Nat. Prod. 1994. Vol. 57. P. 243 - 247.
- Pezzuto Dg., Darrick SHL Kim. Methods of manufacturing betulinic acid. US patent 5.804.575.1997.
- Ruzicka L., Lamberton AH, Christe Ruzicka CW Synthetic approach to betulinic acid. Helv. Chim. Acta. 1938. Vol. 21. P. 1706-1717.