(NH4)2S2O8-Mediated Metal-Free Decarboxylative Formylation/Acylation of α-Oxo/Ketoacids and Its Application to the Synthesis of Indole Alkaloids.

A metal-free method for the formylation/acylation of indoles and ß-carbolines with (NH4)2S2O8 via direct decarboxylative cross-coupling of α-oxo/ketoacids in moderate to good yields is described. The reaction occurs between ambient temperature and 40 °C under mild reaction conditions with commercially available starting materials. This methodology can be expanded to some biologically active indole alkaloids like pityriacitrins, eudistomins Y1 and Y3, and marinacarbolines A-D.

A Cascade Approach for the Synthesis of 5-(Indol-3-yl)hydantoin: An Application to the Total Synthesis of (±)-Oxoaplysinopsin B.

A cascade approach to the synthesis of 5-(indol-3-yl)hydantoin framework has been developed by the reaction of indole with glyoxylic acid/pyruvic acid under a deep eutectic solution, (+)-tartaric acid-dimethylurea. N,N'-Dimethylurea from a deep eutectic solution functions as a reactant as well as a solvent mixture. Isolation of the intermediate, 5-hydroxyhydantoin, and its reaction with indole provides the mechanistic evidence for this reaction. This method was successfully applied in the first total synthesis of an alkaloid, (±)-oxoaplysinopsin B, with an overall yield of 48%.

Access to 1-indolyltetrahydro-ß-carbolines via metal-free cross-dehydrogenative coupling: the total synthesis of eudistomin U, isoeudistomin U and 19-bromoisoeudistomin U.

A highly selective and captivating metal-free cross-dehydrogenative coupling for the cross-coupling of two reactive nucleophiles such as tetrahydro-ß-carboline and indoles is developed. A series of 1-indolyltetrahydro-ß-carboline derivatives were synthesized in excellent to moderate yields. Temperature, time and concentration control resulted in mono indolylation selectively. Moreover, the total synthesis of eudistomin U and isoeudistomin U and the first total synthesis of 19-bromoisoeudistomin U were accomplished.

Metal-Free C-H Functionalization and Aromatization Sequence for the Synthesis of 1-(Indol-3-yl)carbazoles and Total Synthesis of 7-Bromo-1-(6-bromo-1 H-indol-3-yl)-9 H-carbazole.

An operationally simple, metal-free, cost-effective, and mild oxidative cross-coupling protocol for the synthesis of 1-indolyl tetrahydrocarbazoles to afford 1-(indol-3-yl)carbazoles is developed. N-Chlorosuccinimide is used as a mild oxidant for the functionalization of the 1-position of tetrahydrocarbazoles, aromatization of which furnished 1-(indol-3-yl)carbazoles in good to moderate yields without employing protection/deprotection strategy. A naturally rare dibromo 1-(indol-3-yl)carbazole alkaloid was synthesized for the first time in two steps with an overall yield of 64% by applying the same methodology.

Insight into Copper Catalysis: In Situ Formed Nano Cu2O in Suzuki-Miyaura Cross-Coupling of Aryl/Indolyl Boronates.

A ligand-free copper catalyzed Suzuki-Miyaura coupling of 3,5-diiodopyridine with aryl and indole boronates has been explored in good to excellent yields. In situ generation of nano-Cu2O from CuCl2 under the reaction conditions has been discovered for the first time. The generality of the reaction was further demonstrated by the arylation of 5-iodopyrimidine, iodopyridines, iodobenzenes, and diiodobenzenes and resulted in good to moderate yields. Moreover, bisindole alkaloid Scalaridine A has been successfully synthesized in 60% overall yield.

Concise total synthesis of water soluble metatacarboline A, C, D, E and F and its anticancer activity.

The simple, concise, protecting group free and first total synthesis of Metatacarboline alkaloids (abbreviated as Mc) Mc A, C, D, E and F are reported. The core structure of metatacarboline alkaloids has been constructed by the classical Wittig reaction as key step from easily accessible starting materials with 40-75% overall yields. These synthesized compounds have been subjected to evaluate for their anticancer activity using C6 glioma cell lines. Mc D and Mc F showed significant antiproliferative activity, which was confirmed by MTT and Clonogenic assay. FACS analysis showed that Mc D and Mc F arrested the cell cycle at sub G0/G1 and G2/M phase of cell cycle respectively. Further, Western blot analysis and immunohistochemistry of Mc D treated cells revealed activation of caspase dependent downstream signaling which led to apoptosis.

Total synthesis of calothrixin B via sequential Sonogashira coupling/copper-catalyzed oxidative cyclization.

A total synthesis of the antimalarial indolo[3,2-j]phenanthridine alkaloid calothrixin B is reported. The key intermediate, ketoester 11, was assembled using sequential Sonogashira coupling and intra/intermolecular fashioned copper-catalyzed oxidative cyclization reactions.

Total synthesis of ellipticine quinones, olivacine, and calothrixin B.

A direct route to the synthesis of biologically active ellipticine quinones, olivacine, and calothrixin B is described. The prominent key steps involved are Friedel-Crafts hydroxyalkylation followed by oxidation and directed ortho-lithiation reactions of readily available indole-2-carboxylate esters with appropriately substituted pyridine and quinoline carboxaldehydes.

Total synthesis of the marine alkaloid Mansouramycin D.

Mansouramycin D, a cytotoxic alkaloid was isolated from a marine Streptomyces sp. in 2009. The first, simple, and concise route to the total synthesis of Mansouramycin D is reported. The core structure of the isoquinoline ring has been constructed from iminoannulation of 2-alkynylbenzaldehyde followed by oxidation/deprotection and oxidative amination via a three-step sequence from easily accessible starting materials.

Copper catalyzed synthesis of fused benzimidazolopyrazine derivatives via tandem benzimidazole formation/annulation of δ-alkynyl aldehyde.

A novel route to synthesize the biologically active benzimidazolopyrazine core is outlined. The reaction proceeds via tandem benzimidazole formation/annulations of indole, pyrrole and aliphatic δ-alkynyl aldehydes in the presence of copper salts and green solvents with moderate to good yields.

Total synthesis of Calothrixin A and B via C-H activation.

Bioactive indolo[3,2-j]phenanthridine alkaloids Calothrixin A and B have been synthesized by exploiting Pd-catalyzed cross-coupling reaction via C-H activation as a key step starting from 4-methoxycarbazole.

A formal synthesis of lavendamycin methyl ester, nitramarine, and their analogues: a Povarov approach.

A convergent formal synthesis of lavendamycin methyl ester and synthesis of its analogues have been delineated through the Povarov approach. This protocol is also applied to the formal synthesis of nitramarine (3) in good yield.

Synthesis of pyrido[2,3-b]indoles and pyrimidoindoles via Pd-catalyzed amidation and cyclization.

Biologically and pharmaceutically active core structures containing a new class of 4-hydroxy-α-carbolines, dihydropyrido[2,3-b]indoles, pyrimido[4,5-b] and [5,4-b]indoles have been synthesized in good yields via Pd-catalyzed amidation and cyclizations. The keto-enol tautomerism in 4-hydroxy-α-carbolines has been investigated by DFT calculations and spectroscopic techniques. The fluorescence studies of pyrimido[4,5-b] and [5,4-b]indoles were carried out with good quantum yields.

Copper-mediated domino synthesis of pyrimido[4,5-b]carbazolones via Ullmann N-arylation and aerobic oxidative C-H amidation.

New pyrimido[4,5-b]carbazolone derivatives have been synthesized through cascade Ullmann N-arylation and aerobic oxidative C-H amidation reactions catalyzed by CuBr under air and ligand-free conditions.

Synthesis of functionalized ellipticinium and ellipticine derivatives via electrophilic cyclization.

An efficient methodology for the synthesis of highly functionalized ellipticinium and ellipticine derivatives starting from the corresponding 2-bromocarbazoles via an AgOTf or CuI catalyzed electrophilic cyclization of 2-alkynyl-3-carbazolylaldimines is reported.

Synthesis of α-carbolines via Pd-catalyzed amidation and Vilsmeier-Haack reaction of 3-acetyl-2-chloroindoles.

A new class of α-carboline derivatives has been synthesized by Pd(2)(dba)(3)/BINAP catalyzed amidation of 3-acetyl-2-chloroindoles followed by a Vilsmeier-Haack reaction and is reported.

An Efficient, one-pot synthesis of isomeric ellipticine derivatives through intramolecular imino-Diels-Alder reaction.

New analogues of isomeric ellipticine derivatives fused with biologically important pyrroloindole or chromene moiety have been synthesized by utilizing an intramolecular imino Diels-Alder reaction in a single step.

A new entry to polycyclic indole derivatives via intramolecular imino Diels-Alder reaction: observation of unexpected reaction.

A new, efficient, and highly diastereoselective synthesis of polycyclic indole derivatives through intramolecular imino Diels-Alder reaction of aminoanthraquinone with N-prenylated indole-2-carboxaldehydes in the presence of 20 mol % of triphenylphosphonium perchlorate (TPPP) is reported with extremely high cis selectivity in good yield.