Olugbeminiyi O. Fadeyi

Rapid, General Access to Chiral β-Fluoroamines and β, β-Difluoroamines via Organocatalysis

A rapid, general route to enantiopure beta-fluoroamines and beta,beta-difluoroamines has been developed employing organocatalysis in both a two-pot and a one-pot procedure. Both chemical yields (64-82%) and enantioselectivity (94-98% ee) were excellent and represent a significant improvement in the art of preparing chemically diverse beta-fluoroamines from readily available precursors.

Total synthesis of brevisamide.

The second total synthesis of Brevisamide, a marine cyclic ether alkaloid from Karenia brevis, is reported. This streamlined synthesis proceeds in 21 steps, 14 steps longest linear sequence, in 5.2% overall yield and features a key SmI(2) reductive cyclization step to access the tetrasubstituted pyran core.

General access to chiral N-alkyl terminal aziridines via organocatalysis.

A three step, one-pot protocol involving enantioselective alpha-chlorination of aldehydes, subsequent reductive amination with a primary amine, and S(N)2 displacement to afford chiral N-alkyl terminal aziridines in 40-65% yield (74-87%/step) and, in most cases, >90% ee is reported.

A versatile enantioselective synthesis of azabicyclic ring systems: a concise total synthesis of (+)-grandisine D and unnatural analogues.

Closing in on azacines: We have developed a new six step approach for the rapid and enantioselective synthesis of indolizidine, pyrrolo[1,2-a]azepine, and pyrrolo[1,2-a]azocine azabicyclic systems and their respective lactam congeners, which are found in a host of natural products as well as pharmaceutical preparations. This protocol enables a concise enantioselective total synthesis of (+)-grandisine D in 16.4 % overall yield from commercial materials (see scheme).

Enantioselective Total Synthesis of (+)-Amabiline

The first total synthesis of (+)-amabiline, an unsaturated pyrrolizidine alkaloid from Cynoglossum amabile, is reported. This convergent, enantioselective synthesis proceeds in 15 steps (10-step longest linear sequence) in 6.2% overall yield and features novel methodology to construct the unsaturated pyrrolizidine or (-)-supinidine core.

A New Catalytic Cu(II)/Sparteine Oxidant System for β,β-Phenolic Couplings of Styrenyl Phenols: Synthesis of Carpanone and Unnatural Analogs

A new catalytic Cu(II)/sparteine system has been developed to promote beta,beta-phenolic couplings of styrenyl phenols en route to carpanone and related unnatural congeners in yields exceeding 85%.

Access to Highly Substituted 7-Azaindoles from 2-Fluoropyridines via 7-Azaindoline Intermediates.

A versatile synthesis of 7-azaindoles from substituted 2-fluoropyridines is described. C3-metalation and 1,4-addition to nitroolefins provide substituted 2-fluoro-3-(2-nitroethyl)pyridines. A facile oxidative Nef reaction/reductive amination/intramolecular SNAr sequence furnishes 7-azaindolines. Finally, optional regioselective electrophilic C5-substitution (e.g., bromination or nitration) and subsequent in situ oxidation delivers highly functionalized 7-azaindoles in high overall efficiency.

Structure-Based Approach To Identify 5-[4-Hydroxyphenyl]pyrrole-2-carbonitrile Derivatives as Potent and Tissue Selective Androgen Receptor Modulators

In an effort to find new and safer treatments for osteoporosis and frailty, we describe a novel series of selective androgen receptor modulators (SARMs). Using a structure-based approach, we identified compound 7, a potent AR (ARE EC50 = 0.34 nM) and selective (N/C interaction EC50 = 1206 nM) modulator. In vivo data, an AR LBD X-ray structure of 7, and further insights from modeling studies of ligand receptor interactions are also presented.

The Discovery and Synthesis of Brevisamide

Abstract The red tide dinoflagellate Karenia brevis is known to produce a wide range of ladder-frame polyethers including the brevotoxins, brevenal, and brevisin. Considerable interest has been focused on the biosynthesis of these secondary metabolites, and Nakanishi proposed a cascade process based on endo-tet cyclization of a polyepoxide precursor. Subsequently, Jamison showed that the cyclization cascade does indeed occur, but that a 3-hydroxy-tetrahydropyranyl ring must be present in the polyepoxide substrate. In 2008, Wright and coworkers isolated brevisamide, a monocyclic ether alkaloid, containing the requisite 3-hydroxy-tetrahydropyranyl ring, and heralded as the biosynthetic precursors to all the ladder-frame polyethers. This discovery led to a flurry of synthetic activity, and to date, six total syntheses and two formal syntheses of brevisamide have been reported. Here, we will recount the discovery of brevisamide and describe all of the synthetic efforts to date.