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.
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