Chiral Synthesis of Bio-active Compounds by the Asymmetric Cycloaddition Based on the Unique Molecular Design

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Utilizing cycloadducts which were obtained by the Diels-Alder reaction of (R)_s-2-methyl-3-( p-tolylsulfinyl )p ropenoate (A) and menthyl 3-(2-pyridylsulfinyl) acrylate (B) with cyclopentadiene, chiral synthesis of (+)-epi-beta-santalene (ref 1) , (-)-aristeromycin and (-)-neplanocin A (ref 3) were accomplished. Furthermore, starting from the adduct obtained from the cycloaddition of dienophile B and furan , chiral synthesis of (-)-shikimic acid and epi-shikimic acid were achieved (ref. 2 & 6). An important key intermediate for the synthesis of polycyclopenatano ids have been obtained by the D-A reaction of B and cyclohexadiene (ref. 4)On the other hand, dimethyl (R)_s-2-(isoborneol-10-sulfinyl) acrylate (C) has been designed and obtained diastereoselectively starting from dimethyl acetylenedicarboxylate and 1-mercapto- isoborneol. Under the presence of Lewis acid catalyst, the D-A reaction of the dienophile C with cyclopentadiene proceeded highly stereo- and diastereoselective manner to afford a single adduct, which was effectively converted to Ohno's half ester (ref. 5). Since the Ohno's half ester have been transformed into various carbocyclic nucleosides, the present synthesis constitutes the formal synthesis of those carbocyclic nucleosides and would find wide applications.During this investigation, we found 10-mercaptoisoborneol could be a good chiral auxiliary for the synthesis of optically active alkyl sulfoxides, in general (ref. 10). The thiol also turned out to be an excellent chiral auxiliary for the synthesis of optically active organophosphorus compounds (ref 9).Meanwhile, the cycloaddition of 1-methyl-3-oxidopyridinium with various sulfinyl ethenes has been studied. The adducts were effectively converted to 2alpha-tropanol derivatives both in racemic and optically active forms (ref. 7, 8).