Antileukemic agent

In contrast, an excellent yield was obtained for the reaction between 5-iodoimidazole and propargyl alcohol in the absence of Cul to install the 5-alkynyl derivative [10, 41], The adduct was then deprotected to 5-alkynyl- l-P-D-ribofuranosylimidazole-4-carboxamide 58, an antileukemic agent. It is noteworthy that if the Sonogashira reaction was conducted in the presence of Cul, the yield dropped to 19%. 

Representatives of another important class of plant-derived semisynthetic compounds are the camptothecin (27) derivatives, irinotecan (28) and topotecan (29). Camptothecin (27) was originally discovered as an antileukemic agent in a mouse model when isolated from Camptotheca acuminata Decne. Compounds (28) and (29) are both employed in cancer chemotherapy. These substances are important mechanistically because of their activity against the enzyme, topoisomerase I. These compounds were designed to address efficacy and toxicity concerns with the parent compound, camptothecin, and its sodium salt. ... 

Kiss Z, Deli, E, Vogier WR, Kuo )F (1987) Antileukemic agent alk ysophospholipid regulates phosphorylation of distinct proteins in HL60 and K562 ceUs and differentiation of HL60 cells promoted by phorbol ester. Biodiem Biophys Res Common 142 661-666... 

Anderson et al. (67,68) used the mtinchnone generation-DMAD trapping protocol to synthesize various pyrrolizines as potential antileukemic agents, such as 111 and the pyrrolo[l,2-c]thiazoles 112. 

From another Dysidea sponge species, Dysidea avara, the sesquiterpenes avarol, Fig. (9) and avarone, Fig. (10), which show a wide variety of biological activities, were first isolated. Both compounds are potent antileukemic agents in vitro and in vivo. They were determined to be neither direct mutagens nor premutagens, and they displayed antimutagenic activity... 

Theonelladins C 214 and D 215 and niphatesine C 216 are members of a rapidly growing dass of 3-substituted pyridine alkaloids that are known to display important biological activities (Scheme 12.30) [107]. For instance, theonelladins C and D have shown antileukemic and antineoplastic properties while niphatesine C is a known antileukemic agent. 

Potent antileukemic agent, asatone (11), which was isolated from Asarum taitonense Hayata, was synthesized via dimerization of cyclohexa-2,4-dienone (138) generated by PIDA oxidation of o-methoxyphenol (137) [94] (Scheme 11). 

Various antileukemic agents related to methotrexate, such as 5-deazaaminopterin (385), 5-deaza-folic acid (389) <83JOC4852>, 10-deazaaminopterin (386), 10-deazafolic acid (390) <88JOC35>, 5,10-dideazafolic acid (391), 5,10-dideazaaminopterin (387), and its 5,6,7,8-tetrahydro derivative (392) <85JMC914> are also synthetically available by this method. This route is even successful in the preparation of poly glutamate derivatives of antifolates <9iJOC3386>. 

L.A. Paquette and co-workers accomplished the first total synthesis of the antileukemic agent jatrophatrione. " This natural product has a [5.9.5] fused tricyclic skeleton with a trans-BIC ring fusion. The key step in their approach was the Grab fragmentation to obtain the tricyclo[5.9.5] skeleton. The tetracyclic 1,3-diol was monomesylated on the less hindered hydroxyl group and then treated with potassium fert-butoxide, triggering the concerted fragmentation to afford the desired tricyclic product in almost quantitative yield. 

The roridin family constitutes another subclass of the trichothecane macrolides. Two examples of this group are roridin E (148) and baccharin Bj (150). The latter is isolated from the plant Baccharis megapotamica and is a potent antileukemic agent. Structurally, this class of compounds is quite similar to the verrucarins discussed above, with the exception of the replacement of the hydroxypentanoic acid-muconic ester linkage by an ether bond and some additional carbon substitution. 

The O-protected 9-deazaadenosine derivative 329 was transformed to other pyrrolo[3,2-d]pyrimidin-7-yl C-nucleosides (333 and 334) by performing alterations in the sugar subunit (86MI11 93MI7) (Scheme 99). The prepared compounds were active as antileukemic agents, yet were much less active than the parent 9-deazaadenosine (322) (86MI11). 

The reaction has been used in a convenient synthesis of the antibiotic and antileukemic agent botryodiplodin (97)."°... 

Idarubicin, an antibiotic with antineoplastic activity (12 mg/m2 daily by slow IV injection), is indicated in the treatment of acute myelocytic leukemia in adults, including fragment, antigen-binding, classification M through M , in combination with other approved antileukemic agents. 

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