Of nitidine

Scheme 42. Biomimetic synthesis of nitidine (243), fagaronine (244), and oxyterihanine (242) via enamide aldehydes.

Begley and Grimshaw (94) reported a modified synthesis of nitidine (77) by shortening the steps in Kessar s route (88) by using the A -methylbenza-mide (93) under photochemical conditions. However, they failed to obtain benzo[c]phenanthridone by electrochemical means (94) (Scheme 47). 

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. 

Cyclization of aryl and/or heteroaryl groups by the light-induced elimination of halogen acids is a facile and widely applicable process, and has been used as a step in the synthesis of nitidine and avicine salts (104).153 Thus irradiation of (105)... 

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%. 

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... 

A patent has been published covering the synthesis of nitidine-like compounds.Chelilutine has been correlated with nitidine and iso-arnottianamide. ... 

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. ... 

A short synthesis of nitidine involves Mannich cyclization of the cis amine 17 as indicated below... 

An independent synthesis of nitidine has used a nearly parallel route. ... 

The methoxy derivative 27 of nitidine is active in the P388 test and the more resistant L1210 mouse leukemia test. ... 

For syntheses of nitidine and other aromatic benzophenanthridines by a useful modification of the Robinson-Arthur approach, see (a) K.-Y. Zee-Cheng and C. C. Cheng,... 

SCHEME 19.50 Heck followed by Hiyama reactions in the synthesis of nitidine [68]. 

The importance of the use of a Lewis-basic activating reagent is demonstrated in a synthesis of nitidine... 

The aerial part of Zanthoxylum inerme was divided into bark and wood. From the bark, more than 0.07% of nitidine was isolated together with other related alkaloids. By contrast, none of these alkaloids were found in the wood, and 4-methoxy-l-methyl-2-quinoline was the only nitrogeneous compound occurring together with several coumarins and lignans. These results are shown in Table 5.2.2 (75). Nitidine has been shown to have cytotoxic and antitumor activities. 

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... 

Blanchot M, Candito DA, Larnaud F, Lautens M (2011) Formal synthesis of nitidine and NK 109 via palladium-catalyzed domino direct arylation/N-arylation of aryl tiiflates. Org Lett 13 1486-1489... 

Scheme 16.33 Synthesis of nitidine and NK109 using Catellani-type tandem C-H arylation/W-arylation.

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