Application of Cp2TiCl-Promoted Radical-Induced Cyclization: An Expeditious Access to [a]-Annelated Indoles.

An efficient and novel route for assembling pyrrolo/piperido[1,2-a]indoles is portrayed involving a radical-mediated reductive epoxide opening reaction of N-tethered epoxy-indoles that trigger facile intramolecular cyclization followed by an oxidative quenching step. Capitalizing on the operational simplicity of the method involving just two steps and use of an efficient C-C bond-forming reaction, this radical-based protocol enables the modular assembly of an important class of N-fused indole derivatives with versatile functional and structural diversity.

Application of Cp2TiCl-Promoted Radical Cyclization: A Unified Strategy for the Syntheses of Iridoid Monoterpenes.

An expedient approach toward the unified total syntheses of (+)-iridomyrmecin, (-)-isoiridomyrmecin, (+)-7- epi-boschnialactone, (+)-teucriumlactone, and (-)-dolichodial in chirally pure forms starting from readily available (+)-ß-citronellene is delineated combining step economy and simplicity. Highlights include a Ti(III)-mediated reductive epoxide opening-cyclization for the construction of the core cyclopenta[ c]pyran skeleton of the iridoid lactones with complete diastereoselectivity for the newly created bridgehead stereogenic centers. Subsequent transformations facilitate a short access to (+)-teucriumlactone and (-)-dolichodial and formal access to potentially other iridoids.

Diversity-Oriented Approach to N-Heterocyclic Compounds from α-Phenyl-ß-enamino Ester via a Mitsunobu-Michael Reaction Sequence.

Herein we delineate a novel route for the diastereoselective construction of diversely substituted N-heterocyclic ring systems as valuable scaffolds for natural products and pharmaceuticals, starting from an easily accessible prochiral α-phenyl-ß-enamino ester. The reaction sequence relies on the unexplored reactivity of α-phenyl-ß-enamino ester as a nucleophilic partner in the Mitsunobu reaction to forge the N-tethered alkene-alcohol/thiol/amine intermediate, which was subjected to an intramolecular hetero-Michael addition reaction under mild conditions to furnish the respective N-heterocyclic compounds embedded with an exocyclic chiral center in high yields and excellent diastereoselectivities. The methodology is amenable for a broad range of substrates based on a metal-free approach.

Synthesis, SAR and biological studies of sugar amino acid-based almiramide analogues: N-methylation leads the way.

Leishmaniasis, caused by the protozoan parasites of the genus Leishmania, is one of the most neglected diseases endemic in many continents posing enormous global health threats and therefore the discovery of new antileishmanial compounds is of utmost urgency. The antileishmanial activities of a library of sugar amino acid-based linear lipopeptide analogues were examined with the aim to identify potential drug candidates to treat visceral leishmaniasis. It was found that among the synthesized analogues, most of the permethylated compounds exhibited more activity in in vitro studies against intra-macrophagic amastigotes than the non-methylated analogues. SAR and NMR studies revealed that introduction of the N-methyl groups inhibited the formation of any turn structure in these molecules, which led to their improved activities.