Application of the Bradsher cycloaddition for the syntheses of naproxen and sakyomicin A and glycosidation via glycals and phenyl(bisphenylthio)sulfonium salts: Effect of the glycal structure on the face selectivity

Part 1. Attempts are made for the syntheses of bioactive compounds naproxen and sakyomicin A using the Bradsher cycloaddition as the key reaction. Naproxen, a non-steroidal antiinflammatory compound, has a 6-methyoxy-naphthalene moiety with a chiral substituent at its C-2. The required alkyl chain is appended to the naphthalene nucleus using the Bradsher reaction between a vinyl ether bearing the chiral alkyl chain and an isoquinolinium salt.; The ABC-ring analog of sakyomicin A, an angucycline antibiotic, is the other target. The key reaction in the proposed synthesis of this target molecule is an intramolecular version of the Bradsher reaction, which requires a 3-substituted-4-alkoxy-isoquinoline. The precursors for the chiral alkyl side chain and the 4-alkoxy-isoquinoline are synthesized and an attempt is made to couple them so as to obtain the desired 3-substituted-4-alkoxy isoquinoline.; Part 2. Glycosyl transfer via glycals, activated by phenyl(bisphenylthio)sulfonium salts to a variety of nucleophiles is studied. The method shows preferential {dollar}beta{dollar} selectivity leading to 2-phenylthio substituted 2-deoxy-{dollar}beta{dollar}-glycosides. A series of glycals are examined in order to determine the effect of their structure on the glycosidation stereochemistry. The face selectivity is strongly influenced by the substituents on the glycal. Glycals with rather rigid structures also give {dollar}beta{dollar}-glycosides as the major products. The allylic 3-pseudoequatorial and 4-equatorial substituents have little contribution in the stereochemical outcome of the reaction while allylic 3-pseudoaxial and 4-axail substituents act as major directors.; This glycosidation method is applied to the synthesis of 1-O-phenyl-2-deoxy-{dollar}beta{dollar}-D-fucopyranoside, the AA{dollar}spprime{dollar}-ring analog of aureolic acid.