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A versatile asymmetric synthesis of bicyclic pyrazolidinones through alkaloid-catalyzed formal [3 + 2]- and [3 + 2 + 2]-cycloadditions of ketenes with azomethine imines is described. The methodology was found to be tolerant of ketene and a variety of monosubstituted ketenes (R = alkyl, OAc). The products were formed in good to excellent yields (71-99% for 24 examples, 39 examples in all), with good to excellent diastereoselectivity in many cases (dr 3:1 to 27:1 for 22 examples), and with excellent enantioselectivity for most examples (≥93% ee for 34 products). In the case of most disubstituted ketenes, the reaction proceeded through a [3 + 2 + 2]-cycloaddition to form structurally interesting bicyclic pyrazolo-oxadiazepinediones with moderate diastereoselectivity (dr up to 3.7:1) and as racemic mixtures (3 examples). The method represents the first unambiguous example of an enantioselective reaction between ketenes and a 1,3-dipole.

An efficient environmentally benign route for the synthesis of benzimidazo[2,1-a]isoquinoline has been developed by reacting 2-ethynylbenzaldehyde and related substituted alkynylbenzaldehydes with variously substituted ortho-phenylenediamines and aliphatic amines in ethanol. This method provides a convenient, room temperature, atom-economical, and catalyst-free access to diversely substituted isoquinoline fused benzimidazoles. Regioselectivity of the reaction, as referred to o-phenylenediamines, was confirmed by X-ray crystallography. The reaction was found to occur in three major steps (imine formations, cyclization, and aromatization) and a mechanism has been proposed.

A novel methodology to access alkynyl nucleoside analogs was elaborated. Highly fluorescent 5-alkynylfuropyrimidines were synthesized (97-46%) and their antiviral properties investigated in vitro. Regiochemistry of the functionalization was achieved with the aid of 5-endo-dig electrophilic halocyclization of acetyl 5-p-tolyl- or 5-p-pentylphenyl-2'-deoxyuridine. Structure of one of the resulting nucleosides, 6-p-tolyl-5-iodo-2'-deoxyribofuranosyl-furo[2,3-d]pyrimidin-2-one, was confirmed by X-ray crystallography, and its conformation was compared to related nucleosides. Diverse alkynyl substituents were introduced at the heterobicyclic base C-5 position via Sonogashira coupling of 5-iodo-2'-deoxyribofuranosyl-furo[2,3-d]pyrimidin-2-ones. The resulting compounds had fluorescence emissions of 452 to 481 nm. High quantum yields of 0.53-0.60 were observed for 9-ethynyl-9-fluorenol and propargyl alcohol/methyl ether-modified furopyrimidines. These modified nucleosides, designed in the form of ribose acetyl esters, represent potential tools for fluorescent tagging, studying nucleoside metabolism, 2′-deoxyribonucleoside kinase activity, and antiviral activity. Antiviral assays against a broad spectrum of DNA and RNA viruses showed that in human embryonic lung (HEL) cell cultures some of the compounds showed antiviral activity (EC50 1.3-13.2 μM) against varicella-zoster virus (VZV). The alkynyl furopyrimidine with two p-pentylphenyl substituents emerged as the best compound with reasonable and selective anti-VZV activity, confirming p-pentylphenyl potency as a pharmacophore., Graphical abstract Novel fluorescent nucleoside analogs, 5-alkynylfuropyrimidines show high quantum yields (0.53-0.60). Assays in VZV cell cultures are presented.Image 1, Highlights • A new synthetic protocol was established to access novel class of nucleosides, 6-alkynyl furopyrimidines. • Antiviral activity (EC50 1.3-13.2 μM) in human embryonic lung (HEL) cell cultures against varicella-zoster virus (VZV); inhibition against TK- VZV strain exceeded that of acyclovir. • Emission wavelength values 453-481 nm (λex = 360 nm) were observed for 6-alkynyl furopyrimidines. • High quantum yields (0.53-0.60) observed for selected compounds. • X-ray crystallography confirmed structure of 6-p-tolyl-5-iodo-2'-deoxyribofuranosyl-furo[2,3-d]pyrimidin-2-one.