Alkaloids camptothecin

The pentacyclic plant alkaloid camptothecin has been a popular synthetic target because of its antitumor activity. Retrosynthetic disconnection to tricyclic intermediate A and chiral lactone B followed from multistrategic planning. 

The protected E-ring moiety of (S)-camptothecin has been prepared in enantio-merically enriched form by the enzymatic resolution of a triester with PLE in a pH 7 phosphate buffer-acetonitrile (5 1) solution (Figure 6.7). The alkaloid camptothecin is an inhibitor of the enzyme topoisomerase and some of its derivatives are anticancer drugs [52]. 

The most important aspect of coralyne is its ability to inhibit DNA relaxation in a fashion significantly similar to the most potent antitumour alkaloid camptothecin, which is known to exert this property [242], Presumably, the most notable biological action of these alkaloids appears to be topoisomerase inhibition [238-242], which has direct relevance to their DNA intercalating property. In this context. Pilch et al. [167] described a mixed binding mode model (Fig. 16) in which the protoberberine structure constitutes portions that can intercalate or bind to the minor groove of DNA. Wang et al. [240] demonstrated that coralyne (Ci) and several of its derivatives (Ce to Ch) (Scheme 5), including the partial saturated... 

Examples of inhibitors of chromatin function derived from flowering plants (Fig. 80) are etoposide (lignan) and alkaloids camptothecin, Vinca alkaloids, and 7 epitaxol. The rhizome of Podophyllum peltatum L. (May apple, Berberidaceae) has been used to remove warts and to relieve the bowels from costiveness since very early times. It contains podophyllo-toxin, a cytotoxic lignan from which etoposide (Vepesid ), which is used to treat lung cancer, lymphomas, and leukemias on account of its ability to inhibit the activity of... 

A combination of a reductive amination and a Michael addition has been used to synthesize the anticancer alkaloid camptothecin (2-955) via 2-954, starting from the quinoline carbaldehyde 2-953 and benzylamine (Scheme 2.214) [487]. 

AmnaT, Puri SG, Verma V, Sharma JP, KhajuriaRK, MusarratJ, Spiteller M, Qazi GN, Bioreactor studies on the endophytic fungus Entrophospora infrequens for the production of an anticancer alkaloid camptothecin, Can J Microbiol 52 189-196, 2006. 

The pentacyclic quinoline alkaloid camptothecin (1) contains in addition to the quinoline system (rings A and B) a pyndone unit (ring D) and a lactone ring (E) Compound 1 also includes one stereogenic center (at C-20), which has the -configuration... 

Irinotecan (1) is a derivative of the pentacyclic quinoline alkaloid camptothecin (2) the latter was first isolated from the heartwood of the tree species Camptotheca acuminata (Nyssacea) by Wall et al. in 1966.1 Two years later A. T. McPhail and G. A. Sim determined the structure of 2 by X-ray analysis.2... 

Camptothecins. The alkaloid camptothecin from Camptotheca acuminata (Nyssaceae) and Mappiafoetida (Icacinaceae) has a pyranoindolizoquinoline structure (Phe pyridine C4N C5N C5L) involving the fusion of quinoline (Phe pyridine), indolizidine (C4N C5N ) and C5 lactone (C5L) rings. Camptothecin is a topoisomerase I inhibitor and is a potent cytotoxic and antitumour compound that is used clinically as an anticancer... 

A variety of plant substances with planar, polycyclic, aromatic structures can intercalate with DNA, examples being the quinoline alkaloid camptothecin and the furanocoumarin phenolic psoralen (Table 12.1). A variety of plant-derived anthraquinones and naphthoquinones bind to DNA and it is notable that the structurally related anthraquinones mitox-antrone and adriamycin are clinically employed as anticancer drugs (Table 12.1). DNA-binding compounds that interfere with DNA repair, DNA replication and gene expression are cytotoxic and have potential as anticancer agents (see Chapter 9). 

Radical precursors with a five-membered heteroarene for ring D of the important anticancer and antiviral alkaloids (Camptothecin, Mappicine, Nothapodytine B, and Nothapodytine A), l-(2-halo-3-phenylprop-2-en-l-yl]-l//-pyrrole-2-carbonitriles 163, ( )/(Z) mixture, were synthesized in high yields (87-96%) by alkylation of l//-pyrrole-2-carbonitrile with the cinnamyl bromides 162 using KOH in DME (Equation 30) <2002J(P1)58>. 

The alkaloid camptothecin (66) from Camptotheca acuminata (Nyssac.) has created much interest recently.When tested against leukaemia L-1210 in mice... 

A radical-based quinoline ring synthesis was developed with the total synthesis " of the anti-cancer alkaloid camptothecin in mind. The sequence below shows the construction of the ring skeleton of camptothecin and suggests a mechanism for the process. 

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. 

Schweta S, Bindu JH, Raghu J, Suma HK, Manjunatha BL, Kumara PM, et al. Isolation of endophytic bacteria producing the anti-cancer alkaloid camptothecine from Miquelia dentate Bedd. (Icacinaceae). Phytomedicine 2013 20(10) 913-7. 

Schweta S, Gurumurthy BR, Ravikanth G, Ramanan US, Shivanna MB. Endophytic fungi from Miquelia dentata Bedd., produce the anti-cancer alkaloid, camptothecine. Phytomedicine 2013 20(3 -4) 337 2. 

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]. 

Glycosides of the antitumour alkaloid camptothecin and an enantiomer of gilvocarcin M are mentioned in Chapter 3. 

Many feeding experiments (72, 144) have established that, as monoterpenoid indole alkaloids, camptothecin is also generated from tryptamine and secola-ganin. From strictosidine, a nine-membered ring intermediate can be derived via strictosamide (73) by oxidative cleavage of the C2-C7 double bond. A C2--C6 condensation occurs and, finally, camptothecin, is generated (Fig. 5.2.21). 

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