Sepehr Sarshar

Imidazole libraries on solid support

The method of synthesis of highly substituted imidazole libraries on solid support using an aldehyde, an amine and a 1,2-dione in the presence of NH4OAc is described. The synthesis was accomplished by attaching the aldehyde or amine component to Wang resin via ester or ether linkages. A class of unsymmetrical bis-imidazoles has also been prepared without any need for selective protection of the synthetic intermediates.

Solid phase synthesis of pyrroles derived from a four component condensation

Abstract The first synthesis of tetra- and penta-substituted pyrroles via a 1,3-dipolar cycloaddition of alkynes to polymer bound munchnones is reported. These munchnones are generated in a single step from a four component condensation product of an aldehyde, an amine, a carboxylic acid and an isocyanide. The process produces pyrroles in good overall yield and high purity.

Convenient routes to symmetrical benzils and chiral 1,2-diaryl-1,2-diaminoethanes, useful controllers and probes for enantioselective synthesis

Abstract Pathways for the diastereoselective preparation of chiral 1,2-diaryl-1,2-diaminoethanes from ArCOOH, ArCHO or ArBr are described.

X-ray crystallographic studies provide additional evidence that an enzyme-like binding pocket is crucial to the enantioselective dihydroxylation of olefins by OsO4-bis-cinchona alkaloid complexes

X-Ray crystallographic analysis on single crystals and 1H NMR studies in solution of various bis-cinchona alkaloid derivatives reveal a general preference for a conformation which possesses a U-shaped binding pocket with favorable dimensions for the inclusion of olefinic substrates and the acceleration of face selective dihydroxylation by a proximate pentacoordinate OsO4.

2,4,5-trisubstituted imidazoles : Novel nontoxic modulators of P-glycoprotein mediated multidrug resistance. Part 1

Solution-phase combinatorial chemistry was applied to the optimization and development of clinical candidate OC144-093 (22), a novel and nontoxic modulator of P-glycoprotein mediated multidrug resistance.

Remarkably effective and simple syntheses of enantiomerically pure secondary carbinols from achiral ketones

Abstract The chiral oxazaborolidine (1)-catalyzed reduction of the ketones 2, 6 and 8 has provided simple access to the chiral secondary carbinols 3, 7, and 9 in very high enantiomeric purity.

The structure of the 2-methylacrolein boron trifluoride complex in the crystalline phase and in solution

Abstract A crystalline 1:1 complex of BF3 and 2-methylacrolein has been isolated and shown to have molecular structure 1. 1H NMR molecular dynamics and NOE studies have demonstrated that the same s-trans structure of the complex predominates at 185 K in CD2Cl2 solution. The relevance of these results to the enantioselectivity of Diels-Alder reactions with chiral Lewis acids is discussed.

Correlation of the structure of chiral o,o′-bisphenol-Ti(IV) complexes with ligand electronic effects. A relationship between Lewis acidity and angle strain

Abstract The electron deficiency of Ti(IV) in complexes with chiral o,o′-bisphenols influences the CArue5f8Oue5f8Ti angle which, in turn determines the topology of the most stable (or easily formed) cyclic complex.

X-ray diffraction studies of crystalline trihalomethyl ketones (RCOCX3) reveal an unusual structural deformation about the carbonyl group

Abstract X-ray crystallographic studies of a set of trihalomethyl ketones ( 4, 5 , and 6 ) indicate that the carbonyl oxygen is displaced significantly toward the trihalomethyl group, probably as a consequence of oxygen lone pair delocalization into the σ* orbital of COue5f8X 3 .

Techniques for single-compound synthesis

Traditionally, lead discovery in the pharmaceutical industry is achieved either through rational drug design or high throughput screening of sample collections, plant extracts or animal tissues. Subsequently, medicinal chemists optimize these leads through single-compound synthesis. Such a process may take 6.5 years on average before producing suitable clinical candidates [1]. With the advent of high throughput biological screening, the synthesis of compounds has become the bottleneck in drug discovery. Such a wide gap in efficiency between medicinal chemistry output and high throughput screening outlines the need for novel high throughput synthetic technologies geared towards the automated production of large libraries of small organic molecules.