Uldis Peipiņš

Synthesis of novel lupane triterpenoid-indazolone hybrids with oxime ester linkage.

Graphical abstract Figure. No Caption available. HighlightsNovel lupane triterpenoid‐indazolone hybrids with oxime linkage are obtained.This is the first report on oxime esters derived from betulonic and betulinic acid at their C(28).X‐ray structure of the hybrid molecule is reported.Purification procedure for betulonic acid via its cyclohexylammonium salt is developed. Abstract An efficient protocol for the synthesis of novel lupane triterpenoid‐indazolone hybrids with oxime ester linkage has been developed from naturally accessible precursor betulin. For the first time a series of betulonic acid‐indazolone hybrids have been synthesized via an acylation of corresponding 6,7‐dihydro‐1H‐indazol‐4(5H)‐one oximes with betulonic acid chloride. Diastereoselective reduction of the obtained betulonic acid conjugates with NaBH4 resulted in a formation of betulinic acid‐indazolone hybrids in excellent yields. The configuration of the key compounds has been fully established by X‐ray and 2D NMR analysis.

Betulin 3,28-di-O-tosyl­ate

The title compound, C44H62O6S2 {systematic name: (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-[(tosyloxy)methyl]icosahydro-1H-cyclopenta[a]chrysen-9-yl 4-methylbenzenesulfonate}, was obtained by tosylation of naturally occurring betulin. All the cyclohexane rings adopt chair conformations and the cyclopentane ring adopts a twisted envelope conformation, with the C atom bearing the tosylmethyl substituent forming the flap. In the crystal, molecules form a three-dimensional network through multiple weak C—H⋯O hydrogen bonds.