No abstract

Reactions of betulin, its diacetate, and 17-acetoxy-28-norlupan-3-one with dichlorocarbene generated from chloroform follow the [1 + 2]-cycloaddition pattern leading to the corresponding adducts in moderate to quantitative yield. In the reaction with betulin, [1 + 2]-cycloaddition is accompanied by dichlorocarbene attack on the primary hydroxy group to give the corresponding halogen derivative and formate. The addition of dichlorocarbene to betulin is strictly stereoselective, while the reaction with betulin diacetate affords a mixture of two diastereoisomers at a ratio of 95 : 5. The reaction of betulin diacetate with dibromocarbene yields dibromocyclopropane derivative which can be converted into the the corresponding diol.Compounds containing a cyclopropane fragment were found among various naturally occurring biologically active substances, including steroids and terpenoids. The synthetic and biological potentials of these compounds are difficult to overestimate [1,2]. The presence of an isopropenyl group in molecules of lupane triterpenoids makes it possible to introduce a functionalized cyclopropane moiety into the side chain, thus opening wide prospects in modifying the lupane skeleton at C 20 and giving rise to new approaches to design of complex molecules on the basis of accessible lupane triterpenoids and to search for new kinds of biological activity in the series of these compounds. Among lupane derivatives containing a cyclopropane fragment, esters derived from betulin (Ia) and tetramethylcyclopropanecarboxylic and permetrinic acids have been reported [3].The double bond in compound Ia and its derivatives can be involved in isomerization, oxidation, reduction, and allylic bromination [4][5][6][7][8]. However, despite wide synthetic potential, cyclopropanation of betulin (Ia) was not studied. In particular, such experimentally simple and convenient procedure as dihalocyclopropanation of double bond under conditions of phase-transfer catalysis was not applied to betulin [9].While performing the present study, a publication appeared [10], where a high antituberculous activity was predicted by computer simulation for 20,29-dichloromethanolupane-3β,28-diol and a procedure was proposed for the synthesis of this compound in 35% yield from betulin (Ia) in one step under conditions of phase-transfer catalysis. However, no spectral data were given, and the melting point reported therein, 293-294°C, considerably differed from the melting point of a sample prepared by us.We have found that the reaction of betulin (Ia) with dichlorocarbene generated from CHCl 3 by the action of 50% aqueous sodium hydroxide in the presence of benzyltriethylammonium chloride at room temperature gives a mixture of dichlorocyclopropanated diol II, formate III, and chloride IV (Scheme 1). The reaction follows the [1 + 2]-cycloaddition pattern and is accompanied by dichlorocarbene attack on unshared electron pair on the oxygen atom of the primary hydroxy group [11,12]. Diol II was isolated in 55% yield by column chromatography. Formate...

The oxidative decarboxylation of betulonic, 3,20-dioxo-29-nor-lupan-28-oic, dihydrobetulonic acids with Pb(OAc) 4 in the presence of Py, Cu(OAc) 2 , CF 3 COOH or with PhI(OAc) 2-I 2 leads to 28-nor-lup-16(17)-enes and 28-nor-lup-17(22)-enes, and 17α-acetoxy derivatives. The proportion of regioisomeric olefines is related to a substituent at C-19; the yields of olefines and of acetoxy derivatives depends on reaction conditions and structures of the starting acids. The structures of products were determined by spectroscopic methods.

Steroids U 0300 Cyclopropanation of Betulin and Its Diacetate with Dihalocarbenes. -The title reaction follows the [1 + 2] cycloaddition pattern leading to adducts of type (III), (VII), and (IX). -(KOMISSAROVA, N. G.; BELENKOVA, N. G.; SHITIKOVA, O. V.; SPIRIKHIN, L. V.; YUNUSOV, M. S.; Russ.

The addition of dichlorocarbene generated under phase transfer catalysis conditions to the double bond of betulonic acid occurs stereoselectively and is accompanied by transformation of the carboxy group leading to the dichloromethyl ester and chloride of 3 oxo 20,29 (dichloromethano)lupan 28 oic acid. Together these products, the chloride of the starting betulonic acid is formed depending on the reaction conditions. The reaction of dichlorocarbene with methyl betulonate leads to the corresponding cyclopropane adduct in a quantitative yield.