Domino Semipinacol/Iterative Aldol/Iso-Nazarov Cyclization to Triaryl-cyclopentenone: Enantioselective Synthesis of Combretastatin A-4 Analogues.

A facile domino strategy has been developed for the synthesis of a biologically active cyclopent-2-enone core containing combretastatin A-4 (CA-4) analogues from aryloxirane and aryl aldehyde. This one-pot method involves a sequence of semipinacol rearrangement, iterative aldol condensation, and iso-Nazarov cyclization reactions. The scope of this methodology is further shown in the enantioselective synthesis of 5-hydroxy-cyclopent-2-enones using the Sharpless AD catalyst. Biological studies reveal that (S)-enantiomers exhibit better inhibitory activity against cell proliferation than (R)-enantiomers.

A Domino Aza-Piancatelli Rearrangement/Intramolecular Diels-Alder Reaction: Stereoselective Synthesis of Octahydro-1 H-cyclopenta[ cd]isoindole.

For the first time, an efficient one-pot method for the construction of an angularly fused 5-6-5 aza-tricyclic framework has been developed in a highly stereoselective manner. This domino reaction is a novel combination of aza-Piancatelli rearrangement and intramolecular Diels-Alder reaction, which readily furnishes hexahydro-2a,5-epoxy-cyclopenta[ cd]isoindole adducts, bearing six contiguous stereogenic centers in very good yields. The BBr3-mediated cleavage of the oxa-bridged adduct results in the formation of octahydro-1 H-cyclopenta[ cd]isoindole, an aza-tricyclic BCE core of a gracilamine alkaloid.

One-Pot Synthesis of Structurally Diverse Iminosugar-Based Hybrid Molecules.

A one-pot iminium-ion-based strategy has been developed for the synthesis of structurally novel iminosugar-based hybrid molecules. Iminium ion derived from l-rhamnose lactol-mesylate reacted with electron-rich aromatic systems in an inter/intra molecular fashion to furnish pyrrolidine-based iminosugar C-aryl glycosides with a high degree of stereoselectivity. Iminium ion also reacted readily with active methylene compounds such as 4-hydroxycoumarin, 4-hydroxyquinolinone, and lawsone to provide iminosugar C-coumarin/quinolinone/naphthoquinonyl glycosides in very good yields. Azomethine ylide generated from an iminium ion derivative underwent dipolar cycloaddition reaction with 1,4-quinones to furnish novel isopyrrolonaphtho/anthroquinon-based iminosugar-hybrids. The preliminary cytotoxic activities of some of the synthesized iminosugar-hybrids have been assayed against various human cancer cell lines and some of the hybrid molecules exhibited promising anticancer activities.