Betulin Derivatives

Abstract
Betulin and betulinic acid are lupane-type pentacyclic triterpene widely distributed in plant kingdom are commercially obtained from Betula species plants. A variety of biological actions have been recognized to betulin derivatives such as anti-HIV, anti-cancer, anti-inflammatory and anti-malarial. Betulin and betulinic acid (BA) are broadly isolated from white birch bark selectively inhibits the growth of HIV-1. However, the poor water solubility of betulin hinders its pharmacological effectiveness and inspires to find some better hydrophilic derivatives. Here we have summarized various betulin and betulinic acid derivatives obtained from different synthesis routes with distinctly more effectiveness than native molecules as potent

These positions have been widely studied for bio-chemical modifications to yield derivatives for their structure-activity relationship (SAR) studies. Betulinic acid is pharmacologically more active obtained by betulin in two steps yielding up to 75% to supplied substrate at commercial level (Kim et al., 1997). It is clear from the chemical structure of betulin that most of the betulin derivatives presented in this review are lipophilic and thus poorly soluble in water. This may have significant role in explanation of the results of the bioactivity assays that have been carried out mainly in cell cultures. Observed differences in bioactivity between different modified betulin derivatives may be explained at least partly by different distribution constants between these analogs. An essential component of preclinical development of a drug is the exposure of its mammalian metabolism. Few studies have been carried out in vitro to predict and prepared potential mammalian meta-bolites of betulin, betulinic and betulonic acid by utilizing various microorganisms (Mao, Feng et al. 2012, Grishko, et al. 2013, Schwab, et al. 2013,Chatterjee et al., 2000, Kouzi et al., 2000, Akihisa et al., 2002). Betulinic acid is reported non-toxic up to 500 mg/kg body weight doses in mice (Pisha et al., 1995) while its pharmacokinetics and tissue distribution in mice has also been studied (Udeani et al., 1999,Smith, 2007, Jäger, et al. 2008). The therapeutic management of HIV infection depends on the availability of potent and specific chemical inhibitors of virus replication. Currently, the majority of clinically available anti-HIV drugs target reverse transcriptase (RT) or protease (PR), the two key viral enzymes. RT inhibitors include both nucleoside