Diastereoselective synthesis and structural elucidation of dammarane hollongdione pyrazolines

An efficient multistep synthesis of novel substituted pyrazoline derivatives linked to a dammarane scaffold was developed for the first time. Initially, ozonolysis of one of the main metabolites of Dipterocarpus alatus - 3β-hydroxy-dipterocarpol afforded natural 3β-hydroxy-hollongdione, which was subsequently subjected to a Claisen–Schmidt condensation to furnish a derivative bearing a [3-(pyridin-2-yl)-prop-2-en-1-one]-fragment at C17 and the E-configuration of the double bond was confirmed by spectral analysis. Cycloaddition of the enone intermediates with formyl or acetyl hydrazides produced a mixture of S- and R-diastereomers in a 55:45 ratio, which were successfully separated by HPLC. The most prominent distinguishing feature between the R- and S-isomers was the chemical shift of the H-17 proton, appearing at δ 2.62 and δ 2.67, respectively. Additionally, the R-isomer exhibited a more downfield resonance for the Ha-3′ proton and a relatively upfield shift for the Hb-3′ proton.