Bagineni Prasad

A new route to indoles via in situ desilylation–Sonogashira strategy: identification of novel small molecules as potential anti-tuberculosis agents

A new Pd/C-mediated tandem reaction has been developed for the one pot synthesis of indoles containing an o-(RSO2NH)C6H4 group at the C-2 position. The methodology provided novel indoles as inhibitors of Mycobacterium tuberculosis H37Rv chorismate mutasein vitro representing the first example of chorismate mutase inhibition by a heteroarene based small molecule.

Novel thieno[2,3-d]pyrimidines: their design, synthesis, crystal structure analysis and pharmacological evaluation.

Novel thieno[2,3-d]pyrimidines containing a cyclohexane ring fused with a six- or five-membered heterocyclic moiety along with a benzylic nitrile were designed as potential inhibitors of PDE4. Expeditious synthesis of these compounds was carried out via a multi-step sequence consisting of a few key steps such as Gewald reaction, Dieckmann type cyclisation and Krapcho decarboxylation. This newly developed strategy involved construction of the thienopyrimidine ring followed by the cyclohexanone moiety and subsequently the fused heterocyclic ring. A number of thieno[2,3-d]pyrimidine based derivatives were synthesized using this method some of which showed promising PDE4B inhibitory properties. One of them was tested for PDE4D inhibition in vitro and dose dependent inhibition of TNF-α. A few selected molecules were docked into the PE4B protein the results of which showed good overall correlations to their observed PDE4B inhibitory properties in vitro. The crystal structure analysis of representative compounds along with hydrogen bonding patterns and molecular arrangement present within the molecule is described.

A new approach to construct a fused 2-ylidene chromene ring: highly regioselective synthesis of novel chromeno quinoxalines.

Regioselective construction of a fused 2-ylidene chromene ring was achieved for the first time by using AlCl(3)-induced C-C bond formation followed by Pd/C-Cu mediate coupling-cyclization strategy. A number of chromeno[4,3-b]quinoxaline derivatives were prepared by using this strategy. Single crystal X-ray diffraction study of a representative compound e.g. 6-(2,2-dimethylpropylidene)-4-methyl-6H-chromeno[4,3-b]quinoxalin-3-ol confirmed the presence of an exocyclic C-C double bond with Z-geometry. The crystal structure analysis and hydrogen bonding patterns of the same compound along with its structure elaboration via propargylation followed by Sonogashira coupling of the resulting terminal alkyne is presented. A probable mechanism for the formation of 2-ylidene chromene ring is discussed. Some of the compounds synthesized showed anticancer properties when tested in vitro.

A catalyst-free rapid, practical and general synthesis of 2-substituted quinazolin-4(3H)-ones leading to luotonin B and E, bouchardatine and 8-norrutaecarpine

A remarkably rapid but microwave/ultrasound/catalyst-free method has been developed for the construction of a quinazolin-4(3H)-one ring using formamide as an efficient ammonia precursor and PEG-400 as an effective solvent. The methodology afforded various 2-substituted quinazolin-4(3H)-one derivatives in good yield via a three-component reaction of isatoic anhydride, aldehydes and formamide in air. This single methodology was extended successfully to the synthesis of several alkaloids e.g. leutonin B and E, bouchardatine and 8-norrutaecarpine.

Pd-catalyzed isocyanide insertion/nucleophilic attack by indole C-3/desulfonylation in the same pot: a direct access to indoloquinolines of pharmacological interest

A new, simple and straightforward cascade reaction involving the Pd-catalyzed isocyanide insertion followed by a nucleophilic attack by the indole C-3 has been developed. The methodology afforded a diverse and unique class of indolo[2,3-b]quinolin-11-amines as potential cytotoxic agents some of which were evaluated in zebrafish.

New MCR based on intramolecular Heck reaction under aerobic conditions: a direct access to cytotoxic fused N-heterocycles

We report a new MCR involving the reaction of isatoic anhydrides, allyl amine and o-bromo arylaldehydes in the presence of Pd(OAc)2, X-Phos and air to afford various isoquinolino[1,2-b]quinazolinones as new cytotoxic agents. The strategy was extended successfully towards the synthesis of a methyl analogue of 7,8-dehydrorutaecarpine.

A greener approach towards double heteroarylation of N, O and S nucleophiles: synthesis of bioactive polynuclear fused N-heteroarenes

A catalyst, ligand and solvent free method for double heteroarylation of N, O and S nucleophiles has been developed for the first time leading towards the synthesis of compounds containing an indole ring fused with pyrrolo-, furo- and thieno[2,3-b]quinoxaline moieties. This general and greener approach afforded novel compounds of medicinal importance.

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