SYNTHESIS OF PAPAVERINE AND QUINOPAVINE SPECIFICALLY LABELED WITH C-14
SYNTHESIS OF PAPAVERINE AND QUINOPAVINE SPECIFICALLY LABELED WITH C-14
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DOI：
10.1002/jlcr.2590100302
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发表时间：
1974-01-01
期刊：
影响因子：
--
通讯作者：
TSOLIS, A
中科院分区：
文献类型：
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作者：
ITHAKISSIOS, SD;TSATSAS, G;TSOLIS, A
合成了1, 4C标记的1-（3，4-二甲氧基苄基）-6，7-二甲氧基异喹啉（罂粟碱）和1, 4C标记的1-（3，4-二甲氧基苯基）-6，7-二甲氧基异喹啉（喹诺伐因）。3，4-二甲氧基苯甲酸-羧基-14 C。(I)在合成所有上述化合物中用作前体，除了标记的4-甲氧基苯基，其中使用3-甲氧基-4-14 C-甲氧基苯甲酸（XII）。3，4-二甲氧基苯甲酰氯14 C（VII）的还原导致形成3，4-二甲氧基苯甲醛-羰基14-C（VIII），由此通过还原相应的14 C-标记的取代硝基苯乙烯（IX）得到2-（3，4-二甲氧基苯基）-2-甲氧基乙胺-2-14 C（XI）。将3，4-二甲氧基苯甲酸-羧基-14 C（I）用于（3，4-二甲氧基苯基）-乙腈-2-14 C（IV）的合成，其中a）通过还原得到2-（3，4-二甲氧基苯基）-乙胺-2-14 C（VI），B）通过碱水解得到（3，4-二甲氧基苯基）-乙酸-2-14 C（V）。在200°C下在不存在以及存在十氢化萘（溶剂）的情况下一起加热相应的酸和胺，或者通过肖滕-鲍曼反应，获得相应的胺，并且它们在三氯氧化磷的存在下环化。在充当催化剂的钯-浮石存在下使3，4-二氢-产物脱氢。N-（3，4-二甲氧基苯基-2-甲氧基乙基-2-14 C）3，4-二甲氧基苯基-乙酰胺（XVI）环化直接得到相应的14 C）3，4-二甲氧基苯基-乙酰胺（XVI）直接得到相应的14 C-标记的罂粟碱。
1‐(3,4‐Dirmethoxybenzyl)‐6, 7‐dimethoxyisoquinoline (papaverine) labeled with14C in either the benzyl or 4‐carbon position and 1‐(3,4‐dimethoxyphenyl) 6,7‐dimethoxyisoquinoline (quinopavine) labeled with14C at the 1,4 or 4‐methoxyphenyl position were synthesized. The 3,4‐dimethoxybenzoic acid‐carboxyl‐14C.(I) was, employed as the precursor in the synthesis of, all the above compounds except the 4‐methoxyphenyl labeled where 3‐methoxy‐4‐14C‐methoxybenzoic acid was employed (XII). The reduction of 3,4‐dimethoxybenzoylchloride14C (VII) led to the formation of 3,4‐dimethoxybenzaldehyde‐carbonyl14‐C (VIII) from which 2‐(3,4‐dimethoxyphenyl)‐2‐methoxyethylamine‐2‐14C (XI) was obtained through reduction of the corresponding14C‐labeled substituted nitrostyrene (IX). 3,4‐Dimethoxybenzoic acid‐carboxyl‐14C (I) was employed in the synthesis of (3,4‐dimethoxyphenyl)‐acetonitrile‐2‐14C (IV) from which a) 2‐(3,4‐dimethoxyphenyl)‐ethylamine‐2‐14C (VI) was obtained on reduction and b) (3,4‐dimethoxyphenyl)‐acetic acid‐2‐14C (V) on alkaline hydrolysis. On heating together at 200°C the corresponding acids and amines in the absence as well as in the presence of decaline (solvent), or by a Schotten‐Bawmann reaction, the corresponding amines were obtained and them cyclized in the presence of phosphorus oxychloride. The 3, 4‐dihydro‐products were dehydrogenated in the presence of palladium‐pumice which acted as a catalyst. The cyclization of N‐(3,4‐dimethoxyphenyl‐2‐methoxyethyl‐2‐14C) 3,4‐dimethoxyphenyl‐acetamide (XVI) gave straightway the corresponding14C) 3,4‐dimethoxyphenyl‐acetamide (XVI) gave straightway the corresponding14C‐marked papaverine.