One-Pot Synthesis of Pyrrole-2-carboxylates and -carboxamides via an Electrocyclization/Oxidation Sequence

An electrocyclic ring closure is the key step of an efficient one-pot method for the synthesis of pyrrole-2-carboxylates and -carboxamides from chalcones and glycine esters or amides. The 3,4-dihydro-2H-pyrrole intermediates generated in situ are oxidized to the corresponding pyrroles by stoichiometric oxidants or by catalytic copper(II) and air in moderate to high yields. A wide range of functional groups are tolerated, and further combination with an in situ bromination gives access to polyfunctional pyrrole scaffolds.

ChemInform Abstract: Radical Addition to Iminium Ions and Cationic Heterocycles

Carbon-centered radicals represent highly useful reactive intermediates in organic synthesis. Their nucleophilic character is reflected by fast additions to electron deficient C=X double bonds as present in iminium ions or cationic heterocycles. This review covers diverse reactions of preformed or in situ-generated cationic substrates with various types of C-radicals, including alkyl, alkoxyalkyl, trifluoromethyl, aryl, acyl, carbamoyl, and alkoxycarbonyl species. Despite its high reactivity, the strong interaction of the radical’s SOMO with the LUMO of the cation frequently results in a high regioselectivity. Intra- and intermolecular processes such as the Minisci reaction, the Porta react…

Synthesis of Lamellarin D Trimethyl Ether and Lamellarin H via 6π-Electrocyclization.

An electrocyclic ring closure of a 2-azapentadienyl anion generated in situ from a chalcone and glycine ester is the key step of an efficient synthesis of the pyrrole core of the lamellarin alkaloids. A recently developed scalable one-pot procedure provides multigram quantities of a 3,5-diaryl-4-iodopyrrole-2-carboxylate intermediate which is transformed in four further high-yielding operations including a one-pot Pomeranz–Fritsch alkylation/cyclization and an Ullmann-type lactone ring closure into the pentacyclic lamellarin skeleton.

ChemInform Abstract: A High-Yielding Modular Access to the Lamellarins: Synthesis of Lamellarin G Trimethyl Ether (Ia), Lamellarin η (II) and Dihydrolamellarin η (Ib).

Synthesis and biological evaluation of a D-ring-contracted analogue of lamellarin D

A D-ring contracted analogue of the strongly cytotoxic marine pyrrole alkaloid lamellarin D was synthesized and investigated for its antiproliferative action towards a wild type and a multidrug resistant (MDR) cancer cell line. The compound was found to inhibit tumor cell growth at submicromolar concentrations and showed a lower relative resistance in the MDR cell line than the antitumor drug camptothecin to which lamellarin D shows cross resistance and with which lamellarin D shares the same binding site.

Synthetic Approaches to the Lamellarins—A Comprehensive Review

The present review discusses the known synthetic routes to the lamellarin alkaloids published until 2014. It begins with syntheses of the structurally simpler type-II lamellarins and then focuses on the larger class of the 5,6-saturated and -unsaturated type-I lamellarins. The syntheses are grouped by the strategy employed for the assembly of the central pyrrole ring.

A high-yielding modular access to the lamellarins: synthesis of lamellarin G trimethyl ether, lamellarin η and dihydrolamellarin η.

ChemInform Abstract: One-Pot Synthesis of Pyrrole-2-carboxylates and -carboxamides via an Electrocyclization/Oxidation Sequence.

An electrocyclic ring closure is the key step of an efficient one-pot method for the synthesis of pyrrole-2-carboxylates and -carboxamides from chalcones and glycine esters or amides. The 3,4-dihydro-2H-pyrrole intermediates generated in situ are oxidized to the corresponding pyrroles by stoichiometric oxidants or by catalytic copper(II) and air in moderate to high yields. A wide range of functional groups are tolerated, and further combination with an in situ bromination gives access to polyfunctional pyrrole scaffolds.

CCDC 1055316: Experimental Crystal Structure Determination

Related Article: Dennis Imbri , Natalie Netz , Murat Kucukdisli , Lisa Marie Kammer , Philipp Jung , Annika Kretzschmann , and Till Opatz|2014|J.Org.Chem.|79|11750|doi:10.1021/jo5021823

CCDC 1055315: Experimental Crystal Structure Determination

Related Article: Dennis Imbri , Natalie Netz , Murat Kucukdisli , Lisa Marie Kammer , Philipp Jung , Annika Kretzschmann , and Till Opatz|2014|J.Org.Chem.|79|11750|doi:10.1021/jo5021823