Synthesis and Cytotoxicity of 28a‐Homothiolupanes and 28a‐Homothiolupane Saponins

Abstract

A concise synthesis of 28a-homo-28a-thiolupane triterpenes and the corresponding saponins containing D-mannose, D-idose, L-arabinose and L-rhamnose moieties was elaborated. New triterpenes were obtained from readily available 3-O-allylbetulinal by elongation of the carbon chain by Wittig reaction, followed by hydrolysis of the enol ether, reduction of the elongated aldehyde and nucleophilic substitution of the corresponding mesylate with thiocyanate ion. Saponins were obtained by glycosylation of triterpenes with classical Schmidt

Synthesis of 28a-homoselenolupanes and 28a-homoselenolupane saponins

“…Mesylate 1, readily prepared via the reaction of 3-O-allyl-ichopanol and mesyl chloride, 8 was used for the synthesis of selenolupane triterpenes. Standard synthesis of selenocyanate 3 involves the nucleophilic replacement of sulfonyl ester with potassium selenocyanate.…”

“…18 Regioselectivity was, however, slightly lower than that in the case of the corresponding sulfur analogues. 8 With the exception of α-D-mannopyranoside 10, mixtures of α and β anomers 11-16 of L-arabino, L-rhamno, and D-ido derivatives were obtained as specified in Scheme 2. Selenols are considered highly susceptible to air oxidation leading to diselenides, however, selenol 4 was relatively resistant to oxidation.…”

“…We found, that the heteroatom (oxygen or sulphur) located on the C-17 side-chain is necessary for the anticancer activity of the studied compounds. [6][7][8] Based on the high biological activity of selenium derivatives, we reasoned that replacing these heteroatoms on the C-17 side-chain of the lupane core with selenium could enhance their anticancer effect. These results will broaden our knowledge regarding the synthesis, reactivity and stability of selenium-containing triterpenes and steroids as they are virtually unknown in the literature.…”

Synthesis of S-(28a-homobetulin-28a-yl) thiophosphate, thiophosphonate, and thiophosphinate

“…This study is a continuation of our interest in the synthesis and utility of lupane type triterpenes modified at the C-17 side chain. [9][10][11] …”

“…Recently, we presented a method for the preparation of lupanes with an extended C-17 side chain. [9][10][11] The promising cytotoxicity of homobetulin and homothiobetulin derivatives encouraged us to synthesize novel lupane-type triterpenes bearing thiophosphorus substituents at the C-28a homobetulin position 3 and evaluate the cytotoxicity of these compounds. This study has opened up a new research field in lupane chemistry because lupanes bearing a sulfur atom as a part of the core region, are practically unknown.…”