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

利用（R）_s-2-甲基-3-（对甲苯亚磺酰基）丙酸酯（A）和3-（2-吡啶亚磺酰基）丙烯酸薄荷酯（B）与环戊二烯的Diels-Alder反应，合成了（+）-表-β-檀香烯（参考文献1）、（-）-阿替霉素和（-）-neplanocin A（参考文献3）。此外，以亲二烯体B与呋喃环加成反应得到的加成物为原料，实现了（-）-莽草酸和表莽草酸的手性合成（参考文献2和6）。由B与环己二烯的D-A反应得到了一个重要的合成多环戊醇的关键中间体（参考文献4）。另一方面，以乙炔二甲酸二甲酯和1-巯基异冰片为原料，设计并非对映选择性地合成了（R）_s-2-（异冰片-10-亚磺酰基）丙烯酸二甲酯（C）。在刘易斯酸催化剂存在下，亲二烯体C与环戊二烯的D-A反应以高度立体选择性和非对映选择性的方式进行，得到单一加合物，该加合物有效地转化为Ohno半酯（参考文献5）。由于Ohno的半酯已转化为各种碳环核苷，本合成方法构成了这些碳环核苷的正式合成，并将有广泛的应用。在本研究中，我们发现10-巯基异冰片一般可作为合成光学活性烷基亚砜的良好手性助剂（参考文献10）。硫醇也被证明是合成光学活性有机磷化合物的优良手性助剂（参考文献9）。同时，研究了1-甲基-3-氧化吡啶鎓与各种亚磺酰基乙烯的环加成反应。加合物有效地转化为外消旋和光学活性形式的2 α-托烷醇衍生物（参考文献7、8）。

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).