Preparation of pharmacologically active compounds having 7-azanorbornane skeleton.

1)以前，我们已经通过1，1 ′-双（甲氧羰基）二乙烯胺与取代乙烯的光环合反应制备了各种7-氮杂降冰片烷衍生物。2）由于7-氮杂降冰片烷不能与另一个杂环稠合，我们转而利用1，3-偶极环加成反应合成了7-氮杂降冰片二烯。7-对甲苯磺酰基-7-氮杂降冰片-2，5-二烯-2，3-二羧酸二甲酯与三氟乙腈氧化物或N-苯基三氟乙腈亚胺通过1，3-偶极环加合物的Retro-Diels-桤木反应得到相应的裂变产物，而与N-甲基三氟甲基硝酮通过二烯2，3-位的1，3-偶极环加成得到预期的三环产物。在7-氧杂降冰片-2，5-二烯-2，3-二羧酸二甲酯的情况下获得了类似的结果。3）为了促进氧化物和亚胺的环桤木反应，可以用7-杂降冰片烯代替它们的二烯类似物作为底物。本文研究了N-取代吡咯与N-甲基吡咯烷酸酯在不同条件下的反应，但制备7-氮杂降冰片烯的尝试并不成功。呋喃与马来酸酯反应生成7-氧降冰片烯，再与上述三种三氟甲基-1，3-偶极化合物进行环加成反应，得到目标产物。

1) Previously we have prepared various 7-azanorbornane derivatives by the photocycloaddition of 1,1'-bis(methoxycarbonyl)divinylamine with substituted ethylenes. In the present research, we have developed this reaction with several N-substituted maleimides and bismaleimides to synthesize the corresponding novel 7-azanorbornane derivatives.2) Since these 7-azanorbornanes cannot condense another heterocyclic ring, we then turned to prepare 7-azanorbornadiene to which the 1,3-dipolar cycloaddition would be applied. Dimethyl 7-tosyl-7-azanorborna-2,5-diene-2,3-dicarboxylate with trifluoroacetonitrile oxide or N-phenyl trifluoroacetonitrile imine gave the corresponding fission products by an unusual Retro-Diels-Alder reaction of the supposed 1,3-dipolar cycloadducts, whereas that with N-methyltrifluoromethyl nitrone afforded the expected tricyclic product by the 1,3-dipolar cycloaddition at 2,3-position of the diene. Similar results were obtained in case of dimethyl 7-oxanorborna-2,5-diene-2,3-dicarboxylate. Thus it was found that the oxide and the imine underwent the cycloaddition followed by Retro-Diels-Alder reaction to yield the stable aromatic components.3) In order to facilitate the cycloaddition with the oxide or the imine, 7-heteronorbornenes should be used as substrates in place of their diene analogues. The reaction of N-substituted pyrrols with fumarates was studied under various conditions but an attempt to prepare 7-azanorbornenes was unsuccessful. Then furan was reacted with maleates to give 7-oxanorborn-2-enes, which were in turn subjected to the cycloaddition with the three kinds of above mentioned trifluoromethyl-1,3-dipolar compound to afford the expected products.