U. K. Syam Kumar

An oxidative amidation and heterocyclization approach for the synthesis of β-carbolines and dihydroeudistomin Y

Summary A novel synthetic methodology has been developed for the synthesis of dihydro-β-carboline derivatives employing oxidative amidation–Bischler–Napieralski reaction conditions using tryptamine and 2,2-dibromo-1-phenylethanone as key starting materials. A number of dihydro-β-carboline derivatives have been synthesized in moderate to good yields using this methodology. Attempts were made towards the conversion of these dihydro-β-carbolines to naturally occurring eudistomin alkaloids.

Synthesis of novel 5-alkyl/aryl/heteroaryl substituted diethyl 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates by aziridine ring expansion of 2-[(aziridin-1-yl)-1-alkyl/aryl/heteroaryl-methylene]malonic acid diethyl esters

Summary A novel synthetic methodology has been developed for the synthesis of diethyl 5-alkyl/aryl/heteroaryl substituted 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates (also called 2-substituted pyrroline-4,5-dihydro-3,3-dicarboxylic acid diethyl esters) by iodide ion induced ring expansion of 2-[(aziridin-1-yl)-1-alkyl/aryl/heteroaryl-methylene]malonic acid diethyl esters in very good to excellent yields under mild reaction conditions. The electronic and steric impact of the substituents on the kinetics of ring expansion of N-vinyl aziridines to pyrrolines has been studied. Various diversely substituted novel pyrroline derivatives have been synthesized by this methodology and the products can be used as key intermediates in the synthesis of substituted pyrrolines, pyrroles and pyrrolidines.

An efficient and convenient protocol for the synthesis of tetracyclic isoindolo[1,2-a]quinazoline derivatives

A convenient and one-pot synthesis of tetracyclic isoindolo [1,2-a]quinazoline derivatives via Lewis acid mediated sequential C–N bond formation reactions is reported. This protocol provides a simple and rapid strategy for the synthesis of 12-benzylidene-10,12-dihydroisoindolo[1,2-b]quinazoline derivatives. However, a variety of tetracyclo indole fused quinazoline motifs were synthesized in good yields.

Synthesis of enantiomerically pure N-(2,3-dihydroxypropyl)arylamides via oxidative esterification

Summary A highly efficient synthesis of enantiomerically pure (S) and (R)-isomers of N-(2,3-dihydroxypropyl)arylamides has been developed with good overall yields in a two step process. The key step involves the ring opening of the chiral epoxide with a nitrogen heterocyclic carbene (NHC) and further rearrangement to chiral N-(2,3-dihydroxypropyl)arylamides in high yields and enantioselectivity. During the reaction, no erosion in chiral purity was observed.

Asymmetric synthesis of (–)-leiocarpin A via (–)-(S)-goniothalamin employing Julia–Kocienski olefination

ABSTRACT A concise and enantioselective syntheses of antileukemic natural products such as (–)-(S)-goniothalamin and (–)-leiocarpin A has been accomplished in excellent yields. By employing reported conditions on suitable substrates via Julia–Kocienski olefination, intramolecular lactonization, and subsequently dehydroxylative olefination, (–)-(S)-goniothalamin was synthesized. Then Sharpless asymmetric dihydroxylation–intramolecular Michael addition on (–)-(S)-goniothalamin provided (–)-leiocarpin A. GRAPHICAL ABSTRACT

One pot oxidative dehydration - oxidation of polyhydroxyhexanal oxime to polyhydroxy oxohexanenitrile: A versatile methodology for the facile access of azasugar alkaloids

A unique oxidative dehydration-oxidation of polyhydroxy-oxime (7) to the corresponding ketonitrile (8) in one pot is reported for the first time in carbohydrate literature. Key ketonitrile intermediate (8) upon palladium hydroxide mediated cascade reaction afforded 1-deoxynojirimycin (DNJ) 1b in moderate diastereoselectivity. The cascade reaction involves the conversion of nitrile to amine, heteroannulation, reduction of the imine and subsequent debenzylation to furnish the azasugars. This oxidative dehydration-oxidation and reductive heteroannulation methodology is successfully utilized for the total synthesis of 1-deoxynojirimycin (1b), miglitol (2) and miglustat (3).

One-pot three-component green synthesis of novel dihydrophthalazine-1,4-diones

Green and efficient one-pot three-component synthesis of novel 2-(7-amino-2,2-dimethyl-4-oxo-5-phenyl-4,5-dihydropyrano[2,3-d][1,3]dioxin-6-ylcarbonyl)-2,3-dihydrophthalazine-1,4-diones have been developed by condensing 3-(1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl)-3-oxopropanenitrile with benzaldehydes and Meldrum’s acid using L-proline as catalyst in ethanol at room temperature. The products have been isolated as pure compounds in good yields without using column chromatography.

Dehydrative Annulation Strategy for the Construction of Octahydroindolizine Framework: A Diastereoselective Synthesis of (6R,8aS)-Octahydroindolizin-6-ol

Abstract A dehydrative annulation strategy involving an intramolecular ring closure under a Mitsunobu-type reaction condition has been used for the construction of octahydroindolizine framework successfully. This strategy that was reported to be unsuccessful when applied to a similar system allowed us to perform a diastereoselective synthesis of (6R,8aS)-octahydroindolizin-6-ol [a precursor of (–)-8a-epidesacetoxyslaframine] starting from commercially available chiral (S)-epichlorohydrin via a piperidine intermediate, i.e., (3R,6S)-6-(3-hydroxypropyl)piperidin-3-ol. The methodology has potential to afford a library of optically pure small molecules of pharmacological importance based on the related indolizine framework. GRAPHICAL ABSTRACT

Facile and Simple Synthesis of N-Alkyl and N-Aryl 2-Benzazepines by Nucleophilic Heteroannulation

Abstract An efficient and practical synthesis of N-alkyl and N-aryl 2-benzazepine has been developed. The key steps involved in the synthesis were palladium-mediated Heck reaction followed by aza heterocyclic ring construction by nucleophilic heteroannulation. This four-step sequence synthetic protocol gave moderate to good yields for a wide range of substrates. Subsequently, functionalization of the synthesized compound was carried out under Heck and Suzuki reaction conditions. GRAPHICAL ABSTRACT