Synthesis and Investigation of Novel Spiro-isoxazolines as Anti-Cancer Agents.

A series of structurally diverse 4-bromo spiro-isoxazolines possessing a variety of aromatic and aliphatic substituents at the 3 position, were synthesized through a 1,3-dipolar cycloaddition followed by intramolecular cyclization of a pendant hydroxyl or carboxylic acid group. The biochemical antiproliferative activity was evaluated by using two breast cancer cell lines (MCF-7 and MDA-MB-231) and two prostate cancer cell lines (PC-3 and DU-145) using the MTT viability assay, and the IC values were obtained. Spiro-isoxazoline derivatives bearing a -chloro or an -dichloro aromatic substituent at the 3-position of the isoxazoline showed considerable antitumor activities in all four cell lines with IC value ranging from 43μM to 56μM.

Oxonium Ion Mediated Synthesis of 4-Substituted Spiro-Isoxazolines.

The stereoselective synthesis of 4-bromo-spiro-isoxazolines was achieved in one step through the bromination of various isoxazoles that contain a pendant alcohol or carboxylic acid functional group. Isoxazole bromination leads to a bromonium ion intermediate which opens either by neighboring oxygen lone pair electrons or by intramolecular nucleophilic attack. Single X-ray crystal data provides evidence that the two contiguous stereocenters of the spiro-isoxazoline are formed by the anti intramolecular attack of the nucleophile relative to bromine since there is an anti stereochemical relationship between the spirocyclic ring oxygen and the bromine atom.

A Concise Synthesis of (-)-Cicutoxin, a Natural 17-Carbon Polyenyne.

A concise synthesis of the natural polyenyne -(-)-cicutoxin () is described. After several trials, the successful synthesis commenced with three key fragments, -(-)-1-hexyn-3-ol (), 1,4-diiodo-1,3-butadiene (), and the THP protected 4,6-heptadiyn-1-ol (). Sonogashira coupling of compound with acetylenes and gave the 17-carbon frame, which upon regio-selective reduction of a triple bond with red Al and removal of the THP protecting group afforded the natural product in four linear steps.

First Total Synthesis of the Potent Anticancer Natural Product Dideoxypetrosynol A: Preparation of the "Skipped" ()-Enediyne Moiety by Oxidative Coupling of Homopropargyl Phosphonium Ylide.

Dideoxypetrosynol A is a C30 polyacetylenic alcohol with C symmetry. The first total synthesis of both enantiomers of the potent anti-cancer natural product (+)- and (-)-dideoxypetrosynol A is reported. The key step is an oxidative coupling of a homopropargyl phosphonium ylide to prepare the "skipped" ()-enediyne moiety.

Total synthesis of (+)- and (-)-duryne: a potent anticancer agent from the marine sponge Cribrochalina dura. Establishment of the central double bond geometry and the absolute configuration of the chiral centers.

Duryne is a C30 polyacetylenic alcohol with C2 symmetry. Despite its potent cytotoxicity, its central double bond geometry and the absolute configuration of the chiral centers were not determined. We report the total syntheses of both enantiomers of the anticancer natural product (+)-duryne and the establishment of its stereochemistry by synthesizing both geometric isomers.