Synthesis of Pyrazole Analogs from Argentatin B

Abstract

The pyrazole derivatives 3′-(2-R-phenyl)[3,2-c]pyrazole-16,24-epoxy-25-hydroxy-9,19-cyclostane Va -Vf have been prepared in a three step reaction from argentatin B. The structure of all the compounds synthesized was corroborated by 1 H and 13 C NMR, IR and mass spectroscopy.Argentatin B (I) is an abundant tetracyclic triterpene obtained 1 from the resin of the Mexican guayule (Parthenium argentatum A. GRAY). The skeleton of argentatin B has been found highly similar to steroidal ring and therefore a suitable target for the rational design of potentially useful steroidal-like active molecules. As an extension of our strategy for preparing other argentatin derivatives 2 , herein we report the synthesis of pyrazole derivatives of argentatin B as an attempt to pursue possible biologically active compounds. In this regard it has been reported the synthesis of some steroidallike molecules with pyrazole group fused to the ring A which are currently used as antiinflammatory drugs 3,4 . Our synthetic approach to prepare Va -Vf involves a Claisen-Schmidt condensation of argentatin B (I) with 2-substituted benzaldehydes IIa -IIf under basic medium to give intermediates IIIa -IIIf and subsequent condensation with hydrazine to furnish IVa -IVf. The final pyrazole derivatives Va -Vf were obtained upon treatment of IVa -IVf with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (Scheme 1).The IR data of IIIa -IIIf showed a characteristic band between 1 698 -1 675 cm −1 corresponding to α,β-unsaturated ketone in agreement with the expected ClaisenSchmidt condensation product (Table I). The 1 H NMR spectrum of IIIa -IIIf showed typical signals for the seven methyls 1,5 of argentatin B skeleton, one of them being secondary (δ 0.94 -0.95, J = 8 Hz, H-20) and six being tertiary (δ 0.95 -0.93, H-28;