Ultrasound-assisted multicomponent synthesis of 4H-pyrans in water and DNA binding studies

Abstract

A simple approach to synthesize new highly substituted 4H-pyran derivatives is described. Efficient et 3 n acts as a readily accessible catalyst of this process performed in pure water and with only a 20 mol% of catalyst loading. The extremely simple operational methodology, short reaction times, clean procedure and excellent product yields render this new approach extremely appealing for the synthesis of 4H-pyrans, as potentially biological scaffolds. Additionally, DNA interaction analysis reveals that 4H-pyran derivatives behave preferably as minor groove binders over major groove or intercalators. Therefore, this is one of the scarce examples where pyrans have resulted to be interesting DnA binders with high binding constants (K b ranges from 1.53 × 10 4 M −1 to 2.05 × 10 6 M −1).

A-ring functionalization of cholestane with highly substituted pyrans and 2-aminoisophthalonitriles

“…The first reaction step afforded the α,β-unsaturated carbonyl 3a-f (arbitrary numbering for NMR analysis, Figure 5) in good yields (70-80%), in the presence of t-BuOK (5 equiv) as base. The reaction was quite selective towards the C-2 position of the steroid scaffold (see 1 H and 13 C NMR spectra in SI) (Scheme 1). As we used an excess of benzaldehydes 2a-f (3 equiv), it was expected to have competition between C-2 and C-4 positions, however, no C-4 reaction products were detected in the reaction media.…”

“…After that period, the solvent was removed under reduced pressure, the crude product dissolved in CH2Cl2 (5 mL) and purified by preparative TLC, using a 2:1 mixture of hexane:ethyl acetate as eluent. The compounds were obtained as a mixture of two diastereomers, arbitrary assigned as d1 and d2, from the analysis of 1 H, 13 C NMR, HSQC and HMBC spectra.…”

“…1 H-, 13 C-NMR and HRMS spectra for all new compounds are available in the supplementary file accompanying this paper.…”

“…8 From the literature analysis one can realize that highly substituted pyrans tethered with -NH2 and -CN functionalities at C-2 and C-3 positions (Figure 3), have important pharmacological properties. [9][10][11] Furthermore, it should be highlighted the significance of the 2-amino-3-cyano-4-phenylpyran pharmacophoric fragment (highlighted in red) in AChE inhibitors 12 or even as anticancer 13 and antibacterial 14 molecules (Figure 3). Following our interest in modified steroidal compounds with biological applications, we have looked at the chemical modification of cholestane A-ring, by following a two-step synthetic procedure in order to reach a three-substituted fused pyran heterocyclic ring as depicted in Figure 3.…”

Ultrasound irradiation in heterocycle synthesis: An overview

“…A novel protocol toward the synthesis of highly functionalized 4 H ‐pyrans using Et 3 N as a catalyst was developed [36]. The three‐component reaction of diethyl‐2‐oxosuccinate, malononitrile, and variously substituted aldehyde delivered the pyran derivatives in good to excellent yields at RT within 2 h (Scheme 18).…”