Mukund Jha

The Synthesis and Biosynthesis of Phytoalexins Produced by Cruciferous Plants

Phytoalexins are induced chemical defenses produced by plants in response to diverse forms of stress, including microbial attack. Although phytoalexins from over 30 different plant families have been isolated since Muller first proposed this term in 1940, crucifers were the first plants reported to produce phytoalexins containing sulfur and nitrogen. Most of the cruciferous phytoalexins are biogenetically derived from tryptophan but have rather different chemical structures as well as biological activities. The relatively large amounts of phytoalexins currently required for a diversity of chemical and biological studies are usually obtainable through synthesis, as isolation from plants is difficult and very time consuming. Herein we review work reporting the chemical structures, syntheses, and biosyntheses of cruciferous phytoalexins and present new perspectives on the potential applications of these compounds and analogs.

A Simple Cu-Catalyzed Coupling Approach to Substituted 3-Pyridinol and 5-Pyrimidinol Antioxidants

A convenient approach to 3-pyridinols and 5-pyrimidinols via a two-step Cu-catalyzed benzyloxylation/catalytic hydrogenation sequence is presented. The corresponding 3-pyridinamines and 5-pyrimidinamines can be prepared in an analogous sequence utilizing benzylamine in lieu of benzyl alcohol. The radical-scavenging ability of these derivatives are preliminarily explored and reveal that the increased acidities of the pyridinols and pyrimidinols render them susceptible to more significant kinetic solvent effects when compared to phenols.

Brassinin oxidase, a fungal detoxifying enzyme to overcome a plant defense -- purification, characterization and inhibition.

Blackleg fungi [Leptosphaeria maculans (asexual stage Phoma lingam) and Leptosphaeria biglobosa] are devastating plant pathogens with well‐established stratagems to invade crucifers, including the production of enzymes that detoxify plant defenses such as phytoalexins. The significant roles of brassinin, both as a potent crucifer phytoalexin and a biosynthetic precursor of several other plant defenses, make it critical to plant fitness. Brassinin oxidase, a detoxifying enzyme produced by L. maculans both in vitro and in planta, catalyzes the detoxification of brassinin by the unusual oxidative transformation of a dithiocarbamate to an aldehyde. Purified brassinin oxidase has an apparent molecular mass of 57 kDa, is approximately 20% glycosylated, and accepts a wide range of cofactors, including quinones and flavins. Purified brassinin oxidase was used to screen a library of brassinin analogues and crucifer phytoalexins for potential inhibitory activity. Unexpectedly, it was determined that the crucifer phytoalexins camalexin and cyclobrassinin are competitive inhibitors of brassinin oxidase. This discovery suggests that camalexin could protect crucifers from attacks by L. maculans because camalexin is not metabolized by this pathogen and is a strong mycelial growth inhibitor.

Access to Substituted Dihydrothiopyrano[2,3-b]indoles via Sequential Rearrangements During S-Alkylation and Au-Catalyzed Hydroarylation on Indoline-2-thiones.

An efficient methodology for the synthesis of indole-fused dihydrothiopyrans has been developed from indoline-2-thiones. The protocol involves the synthesis of conjugated ene-yne-substituted indole-sulfides, a gold(III)-catalyzed rearrangement of the ene-yne side chain followed by intramolecular hydroarylation via C3-H functionalization of the indole core. This new synthesis of functionalized tricyclic indole derivatives through sequential rearrangements is quite general in nature.

Au-Catalyzed Synthesis of Thiopyrano[2,3-b]indoles Featuring Tandem Rearrangement and Hydroarylation

Gold(III)-catalyzed synthesis of 14-π electron heteroaromatic thiopyrano[2,3-b]indole is reported using conjugated enyne tethered indole sulfides, featuring skeletal rearrangement conjoined with intramolecular hydroarylation (via C3-H functionalization of the indole core) and oxidative aromatization. Subsequent Pd-catalyzed C-C coupling resulted in a 16-π electron heteroaromatic isothiochromeno[1,8,7-bcd]indole.

Synthesis and anti-tubercular activity of fused thieno-/furo-quinoline compounds

A simple route for preparation of 4-substituted thieno/furo[2,3-c]quinoline compounds is reported in this paper. These compounds were synthesized by using Suzuki coupling between appropriate boronic acid and 2-iodoaniline, followed by reaction with diverse aldehydes in the presence of a catalytic amount of FeCl3. Naphthyridine analogues were also prepared in order to demonstrate the efficacy of the developed method. Further anti-tubercular activity screening of the molecules was undertaken, wherein compounds bearing a fused furo[2,3-c][1,8]naphthyridine skeleton displayed highest activity. The best MIC (minimum inhibitory concentration) value of 5.6 μmol was obtained for 4-(4-methoxyphenyl)furo[2,3-c][1,8]naphthyridine, which is found to be superior to the existing first line anti-tubercular drug ethambutol (7.6 μmol).

Bronsted acid-catalyzed rapid enol-ether formation of 2-hydroxyindole-3-carboxaldehydes

A one-step Bronsted acid-catalyzed synthetic methodology leading to 3-(alkoxymethylene)indolin-2-ones was developed starting from easily accessible 2-hydroxyindole-3-carboxaldehydes. The procedure simply involves a treatment of differently substituted 2-hydroxyindole-3-carboxaldehydes with various alcohols (primary/secondary/tertiary/allyl/propargyl/benzyl) in the presence of a catalytic amount of Bronsted acids such as

Concise syntheses of the cruciferous phytoalexins brassilexin, sinalexin, wasalexins, and analogues : Expanding the scope of the vilsmeier formylation

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