Camptotheca antitumor alkaloids

Only the antitumor alkaloids of Camptotheca have been reported. Davidia involucrata, as tested here, was positive (1/3) (it is sometimes placed in a family of its own, Davidiaceae) three species of Nyssa were negative N. biflora, N. ogeche, N. sylvatica. 

The first mention of the production of the antitumor alkaloid camptothecin (45) by means of Camptotheca acuminata cell cultures was reported by Misawa (735). Sakato and Misawa studied the cell cultures of this plant in more detail, resulting in a cell suspension culture which produced 2.5 /u.g/g dry weight of the alkaloid (734,735), which is considerably lower than the intact plant. 

P. nuda is common in tropical forests from Southern Brazil [142], The MIA strictosamide is the major alkaloid from P. nuda [143], being previously isolated from other plants [144], It is considered an important biosynthetic precursor of the antitumor alkaloid camptothecin, from Camptotheca acuminata [145]. From South American Psychotria species, strictosamide was isolated from P. leiocarpa, P. suterella, P. bahiensis, and/, myriantha [137, 141, 146, 147]. 

Lopez-Meyer M, Nessler CL, McKnight TD (1994) Sites of accumulation of the antitumor alkaloid camptothecin in Camptotheca acuminata. Planta... 

Wall ME, Wani MC, Cook CE, Palmer KH, McPhail AT, Sim GA. 64. Plant antitumor agents. 1. The isolation and structure of camp-tothecin, a novel alkaloidal leukemia and tumor inhibitor from Camptotheca acuminata. J. Am. Chem. Soc. 1966 88 3888-3890. 

Camptothecin (CPT, Cl) is a potent antitumor pentacyclic alkaloid isolated from Camptotheca acuminata Decne. (Nyssaceae family) and originating in China (36, 37). Interest in CPT was sparked by the discovery that its primary cellular target is DNA topo I (38). 10-Hydroxycamptothecin (C2), which also occurs naturally, has a better therapeutic index and is used in China for treating many cancers. 

Camptothecin, a plant alkaloid derived from Camptotheca acuminata, is a potent inhibitor of DNA topoisomerase I. Clinical trials failed to show expected antitumor activity, and the drug produced severe, unpredictable toxicity. The camptothecin analogs irinotecan and topotecan were synthesized to reduce toxicity and improve therapeutic... 

The parent camptothecin alkaloid, isolated from bark of Camptotheca acuminate, has antitumor activity, but its limited water solubility necessitated delivery as ... 

The topo I inhibitor camptothecin (16) is a natural alkaloid isolated from the Chinese tree Camptotheca acuminata it is used to treat gastric, rectal, colon, and bladder cancers. Several natural and synthetic derivatives including 9-amino 17) and 10-hydroxy (IS) camptote-cin, topotecan and irinotecan (20, CPT-ll) / potent antitumor and DNA... 

Several enzymes can react with sterically hindered compounds. For example, the acetate of a tertiary alcohol can be hydrolyzed by papain in buffer-ethyl acetate (pH 6.5) with excellent -value (>400), affording the ( )-alcohol in 49% yield and 98% ee and the (S)-acetate in 50% yield and 99% ee. The remaining (S)-acetate was converted to 20(S)-camptothecin, which is a pentacyclic alkaloid with potent antitumor activity isolated from Camptotheca acuminata. The product ( )-acetate can be converted to the starting racemic acetate chemically in 70% yield (Fig. 10.22). 

Wani M C, Wall M E 1969 Plant antitumor agents. II. The structure of two new alkaloids from Camptotheca acuminata. J Org Chem 34 1364-1367... 

Camptothecin, the potent antitumor and antileukemic agent isolated from the stem wood of the Chinese tree Camptotheca acuminata Nyssaceae, has been the target of numerous chemical syntheses. The first successful synthesis of this unusual alkaloid, characterized by an a-hydroxy-lactone and a pyridone system fused to a five-membered ring, was reported by Stork and Schultz in 1971. A key feature of this synthesis is construction of ring E by a novel lactone annelation involving addition-cyclization of the carbonate of an 0 -hydroxy ester to the tetracyclic Q ,/3-unsaturated lactam (B). 

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