dl-cis-和trans-4-乙酰氨基-2-正丁基-1-二甲氨基-5,6-亚甲二氧基茚满的合成

SYNTHESIS OF DL-CIS-AND TRANS-4-ACETAMIDO-2-n-BUTYL-1-DIMETHYLAMINO-5,6-METHYLENEDIOXYINDAN

以细胞内钙拮抗剂Bu-MDI为先导化合物,设计合成了具有弱钙拮抗作用的4-乙酰氨基取代的茚满衍生物。该目标化合物以胡椒醛为起始原料,经十一步反应制得。合成中对1的格氏反应、2的脱水消除和5的制备等均作了改进,使收率有所提高。对5的硝化产物6的硝基位置经NOE确证,并对目标化合物二对顺、反异构体的比例和生成机制作了讨论。

The title compounds were synthesized from piperonal as starting material through eleven steps. Nitration of indanonc (5) with HNO3-HaSO4 aiforded 6 in 66% yield. 6 waa reducted with Fe/HCl and then acetylated affording 8 which upon reaction with NaBH4 afforded diastereomeric alcohols (9) (a mixture of about 70 % cis form and 30 % trans form). Reaction of 9 with mestyl-Cl ( - 70℃) followed by treatment with Me2NH afforded dimethylaminoindan diastereomers (11) in 52.5% yield and approximate ratio of diastereomers as 9. Isomers of 11 were separated by column chromatography on silica gel/MeOH affording the title compounds, dl-cis-11.HCl and dl-trans-11.HCl. Their yields were 63% and 26% respectively.