New cyclopropane derivatives of betulin were synthesized by attachment of dichlorocarbenes or dibromocarbenes to the double bond of betulin diacetate, followed by the deprotection of hydroxyl groups. The betulin cyclopropane derivative was obtained from 20,29-dihydro-20,29-dichloromethylenebetulin by treatment with lithium in tert-butanol. These compounds were converted into the corresponding derivatives of betulonic acid by oxidation with chromium trioxide. The reduction of oxo group with sodium borohydride led to the corresponding derivatives of betulinic acid. 20,29-Dihydro-20,29-dichloromethylenebetulinic acid proved to be the most cytotoxic toward human melanoma of the Colo 38 and Bro lines and human ovarian carcinoma of the CaOv line (IC50 10 microM). 20,29-Dihydro-20,29-dibromomethylenebetulinic acid inhibited the growth of the Bro melanoma cell line and the CaOv carcinoma cell line practically by 50% at a concentration of 10 microM. The other derivatives of betulinic and betulonic acids were active toward all of the three cancer cell lines at concentrations higher than 10 microM. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2005, vol. 31, no. 3; see also http://www.maik.ru.
The synthesis of pharmacologically active 2¢-deoxynucleoside analogs, namely, 2¢,3¢-dideoxythymidine (I) and 2¢,3¢-dideoxy-3¢-fluorothymidine (II), is described. The proposed approach consists in condensation of the corresponding thioglycosides with silylated thymine using N-bromosuccinimide as a promoter. In the case of compound II, it is shown that the yield and stereoselectivity of this process depend on the equivalent ratio of silylated base and solvent.As is known, 2¢-deoxynucleoside analogs exhibit pronounced antitumor and antiviral properties [1]. Some of these compounds are already used as drugs for the treatment of AIDS, for example, 3¢-azido-3¢-deoxythymidine (AZT), 2¢,3¢-dideoxycytidine (ddC), and 2¢,3¢-dideoxyinosine (ddI)[2]. Nevertheless, the tasks of developing new original approaches to the creation of such drugs and expanding the existing set of techniques for the synthesis of 2¢-deoxynucleosides and their analogs are still urgent.There are two main approaches to the synthesis of 2¢-deoxynucleosides and their analogs: the first is based on the modification of natural nucleosides of the ribo or deoxyribo groups, while the second consists in the condensa-320 0091-150X/06/4006-0320
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.