Camptothecin, 11-methoxy

Genus/species Plant part Camptothecin (%) 9-Methoxy camptothecin (%)... 

The parent, unsubstituted isochromanone has been caused to react with a variety of aromatic amines to prepare Ar-substituted 1,4-dihydro-3(2.ff)-isoquinolones,4 and with amines to give amides.5 The 6,7-methylenedioxy-3-isochromanone was an intermediate in the synthesis of protopine and its allied alkaloids,6 and for the synthesis of the berberine ring system.7 The 6-methoxy analog was prepared as a potential intermediate in a camptothecin synthesis8 and 8-methoxy-4,5,6,7-tetramethyl-3-isochromanonc was an intermediate in the synthesis of sclerin.9 The compound herein described was the basis of a facile synthesis of ( l )-xylopmins,10 and its reaction with hydrazine has been reported.11... 

Ring E is closed by lactonization with 60% sulfuric acid and warming to 115 C. Simultaneously, the methoxy group is activated (by protonation) with respect to nucleophilic attack by the pyridone nitrogen. Ring C is closed via an SN reaction to produce the target molecule, (+)-camptothecin (1). 

Some ring-substituted (hydroxy or methoxy) camptothecin derivatives were either isolated in nature or obtained synthetically [253,264-267]. The 9-methoxy- and 10-methoxycamptothecin are less active, but 10-hydroxy-camptothecin is more active than the parent alkaloid against leukaemia P388 [253, 264], Both camptothecin and its 10-hydroxy derivative are being used in mainland China for the treatment of liver carcinoma and tumours of the head... 

The Indian tree Nothapodytes foetida (syn. Mappia foetida) is an important source of camptothecin, the DNA topoisomerase I inhibitor possessing anti-cancer and anti-HIV activity of significant therapeutic importance. One of the minor components of the plant has been identified as 9-methoxy-20-(S)-mappicine, a tetracyclic derivative of the pentacyclic camptothecin. When the latter compound was treated for a short-time (7 min) with microwave irradiation, it was converted into 9-methoxymappicine ketone with an exceptionally high yield of 95%. This ketone was then easily transformed by baker s yeast into the target compound 9-methoxy-20-(S)-mappicine as illustrated in Fig. 15 [91]. 

A practical six-step synthesis of (S)-camptothecin was developed by D.L. Comins and co-workers." In order to prepare the DE ring fragment, 2-methoxypyridine was Iithiated at C3 with mesityllithium and treated with A/-formyl-A/,A/, A/ -trimethyl ethylenediamine to form an -amino alkoxide in situ. In the same pot, the addition of n-BuLi brought about a directed lithiation at C4 to afford a dianion, which was trapped with iodine and treated with NaBHVCeCIs to give the desired 4-iodo-2-methoxy-3-hydroxymethyl pyridine in 46% yield. 

These alkaloids namely camptothecin, hydroxycamptothecin and methoxy camptothecin... 

A total synthesis of 10-hydroxy- and 10-methoxy-camptothecins has been described, but adequate details of the work are difficult to obtain the overall route used appears to be similar to that adopted by the same group in an earlier synthesis of camptothecin. 

Camptothecin is a quinoline alkaloid isolated from the steins of C. acuminata (Cornaceae) [1], and 10-hydroxy camptothecin and 10-methoxy camptothecin were also obtained as minor alkaloids [2]. C. acuminata is an ornamental plant in China. Campthothecin has also been isolated from both the Apocy-naceae and Rubiaceae plant families. 

Camptotheca acuminata (Nyssaceae) is a tree that grows throughout the southern part of China. From its stem wood, camptothecin has been obtained (160). Camp-tothecin is notable because of its remarkable antitumor and antileukemia activity. The other minor camptothecin analogues that have been obtained are 10-methoxy-camptothecin (161), and 20-deoxycamptothecin (1). 11-Hydroxycamptothecin and 11-methoxycamptothecin have been obtained from the fruit (68, 98). 

Camptothecin (XXVa), hydroxycamptothecin (XXVb), and methoxy-camptothecin (XXVc), three alkaloids of novel structure isolated from the Chinese tree, Camptotheca acuminata, have been shown to have antitumour... 

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