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

• Novel 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.

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.

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