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Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Diastereoselective synthesis and structural elucidation of dammarane hollongdione pyrazolines
Zarema Galimova1, Irina Smirnova1, Alexander Poptsov1
1Ufa Federal Research Center, Russian Academy of Sciences, Ufa Institute of Chemistry, Ufa, Russian Federation.
Abstract:
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.
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