Nitidine chloride

In 1978, the synthesis of the indenoisoquinoline NSC 314622 (Figure 6.16) was reported as the result of an unexpected transformation during a synthesis of nitidine chloride. Given its weak antitumor activity, it was not investigated further. 

Iwamide (156 R = H), a new product from Xanthoxylum arnottianum, has been synthesized from decarine (157), and similar syntheses of arnottianamide (156 R = Me) and isoarnottianamide have been achieved from chelerythrine and nitidine chlorides (Scheme 4). ... 

Total syntheses of nitidine chloride (163) have been achieved from the acid amide (162) and the amide (164) as shown in Scheme 6. Oxidation of the... 

Isoquinolines can be prepared by a Bischler-Napieralski reaction involving a tertiary formamide 1555, which reacts with the dehydration reagent triphosgene to form the anti-tumor active nitidine chloride 1557 [1184]. As regards the reaction mechanism, it can be suggested that the first step affords the same intermediate chloroformate 1556 as the isocyanide-generating process. Then, a Friedel-Crafts acylation-like attack of the iminium cation at the benzene moiety affords the isoquinoline nitidine chloride 1557 in 91% yield. 

Typical procedure. Nitidine chloride [1184] A solution of 1555 (0.102 g, 0.278 mmol) and triphosgene (0.179 g, 0.602 mmol) in acetonitrile (2.5 mL) was stirred at 60 °C (bath temperature) for 0.5 h. After the addition of ice/water, a yellow precipitate was collected by filtration and recrystallized from ethanol/diethyl ether to directly afford nitidine chloride (0.098 g, 91%) mp 285-292 °C. 

Cushman M, Cheng L 1978 Total synthesis of nitidine chloride. J Org Chem 43 286... 

Fan YJ, Zhou J, Li M 1981 Effect of nitidine chloride on the life cycle of Ehrlich Ascites carcinoma cells in mice. Chung-Kuo Yao Li Hsueh Pao 2 46-49... 

Zee-Cheng KY, Cheng CC 1973 Synthesis of 5,6-dihydro-6-methoxy-nitidine and a practical preparation of nitidine chloride. J Heterocycl Chem 10 85-88... 

A common intermediate in the synthesis of benzo[c]phenanthridines is the 2-aryl-l-tetralone, which provides rings A, B, and D of the alkaloid nucleus. In 1973, two independent research groups reported the synthesis of nitidine via the 3,4-dihydro-2-(3,4-dimethoxyphenyl)-6,7-methylenedioxy-(2/7)-naphthalone 29 (Scheme 2). The synthesis of this intermediate was arrived at by two different routes. Kametani ei al. (73JHC31) reduced 3-(3,4-methylenedioxyphenyl)proprionate 21 to the corresponding alcohol 22 with lithium aluminium hydride, which was then converted to the chloride 23 with thionyl chloride. After production of the nitrile 24 by reaction with sodium cyanide and subsequent hydrolysis to the carboxylic acid 25, Friedel-Crafts cyclization of the acid chloride 26 afforded the tetralone intermediate 27. Reaction with l-bromo-3,4-dimethoxybenzene 28 in the presence of sodium amide yielded the tetralone intermediate 29 in an overall yield of 4%. 

The inhibition of mammalian virus nucleic acid polymerase by fagaronine chloride has been studied, as has the mutagenicity of nitidine and O-methyl-fagaronine. The basic optical electronic characteristics of sanguinarine sulphate have been discussed. ... 

In order to confirm this hypothesis, we synthesized the benzophenanthridines 40a and 40b by reaction of benzyne f22af with the key intermediates 38a and 38b. which were obtained from the corresponding tetralones f39a and 39bf by reaction with methylamine and titanium tetrachloride followed by addition of oxalyl chloride (Ref. 20). In view of our success, we then used the same procedure to prepare 40c and 40d. the precursors of avicine f41af and nitidine (41 bf. the latter of which has considerable anti-tumour activity. Compound 40c was obtained by reaction between 38b and the aryne 22f, and 40d by reaction between 38b and 22b. 

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