Diastereoselective Synthesis and Antifungal Activity of Glycosyl Isoxazolines

Abstract

Glycosyl nitrile oxides, generated in situ by reaction of glycosyl oximes (3a, 3b, 4) with N‐chlorosuccinimide and DBU, on 1,3‐dipolar cycloaddition with substituted alkenes resulted in glycosyl isoxazolines (5, 7–28) in diastereoselective manner. The extent of diastereoselection varies with the nature of substituents both in sugar and alkenes. The compounds synthesized were screened in vitro against many fungi wherein two of the compounds (12, 23) showed significant inhibition against Sporothrix schenckii, Trychophyton mentagrophytes, and Cryptococcus neoformans with MIC of 12.5 and 6.25 µg/mL, respectively.     

A facile one-pot three-component synthesis of ferrocene-grafted dispiro pyrrolidine/pyrrolizidine scaffolds through intermolecular [3+2] cycloaddition reaction of ferrocenyl Baylis-Hillman adduct

A one-pot synthesis of ferrocene-grafted dispiropyrrolidine/pyrrolizidine scaffolds has been accomplished in good yields through a facile 1,3-dipolar cycloaddition of various azomethine ylides derived from diketones and secondary amino acids with Baylis-Hillman adduct derived from ferrocene carbaldehyde. The regiochemical and stereochemical outcomes of the cycloaddition reaction were ascertained by X-ray crystallographic studies of one of the cycloadducts.     

A new class of chiral pyrrolidine for asymmetric Michael addition reactions. New mechanism via simple 4+2 type attack of the enamine on the trans-nitrostyrene

A new chiral organocatalyst is described in this paper. A new mechanism for the overall Michael condensation of ketones with nitroolefins using our catalyst is suggested based on molecular modelling studies.     

Highly stereo and chemoselective synthesis of tetra and pentacyclic frameworks using Solid-State Melt Reaction (SSMR)

Benzopyran fused tetra and pentacyclic frameworks have been synthesized by the domino Knoevenagel hetero Diels–Alder (DKHDA) reaction using various 1,3-diones with O-allylated salicylaldehydes and O-propargylated salicylaldehydes in a solvent and catalyst free condition via Solid-State Melt Reaction (SSMR). The reaction requires only a single step operation thus providing potentially bioactive polycyclic heterocycles in high yields.     

Stereoselective preparation of methylenecyclobutane-fused angular tetracyclic spiroindolines via photosensitized intramolecular [2+2] cycloaddition with allene

Irradiation of 3-(hexa-4,5-dienyl)indole derivatives in the presence of 3′,4′-dimethoxyacetophenone by a high-pressure mercury lamp through Pyrex glass gave the corresponding [2+2] cycloaddition products stereoselectively in high yields. The major product was a methylenecyclobutane-fused angular tetracyclic spiroindoline derivative produced by the [2+2] cycloaddition through a parallel orientation. The minor product was a hexahydromethanocarbazole derivative through a crossed orientation. Electron-withdrawing substituents, such as acyl or alkoxycarbonyl, on the indole nitrogen were suitable for this reaction.     

A novel method for the synthesis of 5-substituted 1H-tetrazole from oxime and sodium azide

A simple and efficient protocol is developed for the synthesis of 5-substituted 1H-tetrazoles from various oximes and sodium azide (NaN₃) by using copper acetate as a catalyst.     

Lithium bromide/triethylamine promoted tandem cycloaddition-oxidation reaction: A convenient access to 3-trifluoroacetyl pyrroles from N-alkylidene 2-amino esters and β-trifluoroacetyl vinyl ethyl ether

A convenient lithium bromide/triethylamine promoted tandem cycloaddition-oxidation reaction was developed to afford 3-trifluoroacetyl pyrroles in moderate to good yields from N-alkylidene 2-amino esters and β-trifluoroacetyl vinyl ethyl ether.     

Synthesis of Four- and Five-Membered Heterocycles Derived from an Iminophosphorane

Reactions of an iminophosphorane bearing the Martin ligand with a ketone, an isothiocyanate, and an alkyne gave the corresponding cycloadducts, 1,3,2 u 5 -oxazaphosphetidine, 1,3,2 u 5 -diazaphosphetidine-4-thione, and 1,2 u 5 -azaphosphetine, respectively, while that with dimethyl acetylenedicarboxylate (DMAD) and successive hydrolysis afforded the 1,2 u 5 -oxaphosphole-(2 H )-one. Thermal reactions of the cycloadducts were also studied.     

Synthesis of bridged nicotinates having [n](2,5)pyridinophane skeletons (n=8-14)

Synthesis of various bridged nicotinates 6 having [n](2,5)pyridinophane skeletons (n=8-14) was accomplished by the unique pyridine-formation reaction of methyl propiolate with a series of formyl-substituted (vinylimino)phosphoranes 5, which were prepared from the corresponding cycloalkanones 1 via Vilsmeier-Haack formylation giving chloro-substituted cycloalkenals 2, their thermal and photochemical transformation to formyl azirines 4, and the following ring-opening reactions with triphenylphosphine. The HPLC analysis of [11](2,5)pyridinophane derivatives, (S_p,S)-14 and (R_p,S)-14, showed that these diastereomers rapidly epimerize themselves at room temperature and that their planar-chirality was thermodynamically less stable as compared to the corresponding [11](2,5)cyclophane systems.