Syntheses of C-glycoside natural products via oxocarbenium cationic intermediates

This dissertation highlights studies into the total synthesis of C-glycoside natural products via oxocarbenium cationic intermediates with a brief introduction given in the first chapter. The second chapter examines our approach to the first total synthesis and absolute configuration of the antibiotic (+)-bruguierol C. The key step is the diastereoselective capture of an in situ generated oxocarbenium cation via an intramolecular Marson-type Friedel-Crafts cyclization, which concomitantly generates the chiral quaternary center. The third chapter illustrates the formal syntheses of (+)-brussonol and (+)-abrotanone, attained in a convergent and concise manner, making these syntheses the shortest to date. The key step, as with (+)-bruguierol C, involves the diastereoselective capture of an in situ generated oxocarbenium cation via an intramolecular Marson-type Friedel-Crafts cyclization. A novel methodology that employs catalytic quantities of pyridinium tribromide (Py*Br3) in methanol to chemoselectively deprotect primary TBS ethers in the presence of a variety of other protecting groups and common functional groups is the subject of the fourth chapter. The formal synthesis of the unnatural (-)-neopeltolide core, whose natural antipode has been found to be extremely cytotoxic and has emerged as a promising anticancer lead is discussed in the fifth chapter. Efficient application of the Evans' protocol for the synthesis of 1,3-syn diols via an intramolecular hetero-Michael addition followed by reductive deprotection of the resulting benzylidene acetal allowed for swift access to the ä-lactone. Central to the synthetic approach is a tandem nucleophilic addition-diastereoselective axial reduction of an in situ generated oxocarbenium cation to construct the â-C-glycoside moiety of the neopeltolide core. The final chapter of this dissertation describes the total synthesis of the proposed structure of pochonin J, whose reported structure features a rare á-C-glycoside moiety embedded within a 14-membered macrolactone. Key steps of this convergent synthesis include a chemoselective Wacker oxidation, a stereoselective allylation of an oxocarbenium cation intermediate to assemble the á-C-glycoside fragment, and a ring-closing metathesis (RCM) reaction to forge the 14-membered macrolactone. During our studies directed towards its laboratory synthesis, it was found that the spectroscopic data of the synthesized compound does not correlate to the initially described natural product. (Published By University of Alabama Libraries