Cordycepin 3 -

The nucleoside cordycepin was isolated from cultures of Corofy- ceps militaris and found to be 3 deoxyadenosine Write its structural formula j... 

T. brucei is unable to synthesize purines de novo and, as such, is dependent upon salvage mechanisms from the host. A number of transporters and enzymes are used by T. brucei to accomplish this task, and inhibition of these targets offers promise for development of trypanocides [39]. This strategy has been validated by demonstration that cordycepin (34), a substrate for T. brucei adenosine kinase (TbAK), which terminates RNA synthesis and parasite growth, can cure stage 2 HAT infections in mice when coadministered with deoxycoformycin (35), an adenosine deaminase inhibitor [40]. 

Treatment of cordycepin with nitrous acid, and subsequent hydrolysis of the deaminated product, yields hypoxanthine, indicating that in the adenine moiety the primary amino group is free and the glycosidic linkage involves C7 or C9. The close similarity between the ultraviolet absorption spectrum of cordycepin and those of 9-methyladenine and adenosine63 (9-/3-J>-ribofuranosyladenineMa) favors the latter possibility. The complete stereoisomeric description of cordycepin (XXVIII), formulation of which... 

Cordycepin-1-oxide (XLVIIl) is activated in Ehrlich ascites cells by reduction to cordycepin [220] and a similar A -oxide reduction probably underlies the action of 6-mercaptopurine-3-oxide (XLIX) [221]. 

The first step of this sequence, which is not unique to de novo purine nucleotide biosynthesis, is the synthesis of 5-phosphoribosylpyrophosphate (PRPP) from ribose-5-phosphate and adenosine triphosphate. Phosphoribosyl-pyrophosphate synthetase, the enzyme that catalyses this reaction [278], is under feedback control by adenosine triphosphate [279]. Cordycepin interferes with thede novo pathway [229, 280, 281), and cordycepin triphosphate inhibits the synthesis of PRPP in extracts from Ehrlich ascites tumour cells [282]. Formycin [283], probably as the triphosphate, 9-0-D-xylofuranosyladenine [157] triphosphate, and decoyinine (LXXlll) [284-286] (p. 89) also inhibit the synthesis of PRPP in tumour cells, and this is held to be the blockade most important to their cytotoxic action. It has been suggested but not established that tubercidin (triphosphate) may also be an inhibitor of this reaction [193]. 

In addition to the analogues listed in Table 2.3, cordycepin [302]. 3 -amino-3 -deoxyadenosine [173], and formycin [303] can inhibit the de novo pathway by blocking the phosphoribosylpyrophosphate amidotransferase. Thus, a number ofpurine analogues—after anabolism to nucleoside phosphates—can act as feedback inhibitors, and this inhibition may be the primary cause of their cytotoxicity. 

Several analogues of adenine or adenosine are reported to be incorporated into nucleic acids 2-fluoroadenosine [342], tubercidin [190, 192, 342a], toyacamycin [193,342a], sangivatnycin [342a, b], cordycepin [168,343,344], 4-aminopyrazolo[3, 4-d] pyrimidine [119], formycin [344a], and 9- -D-arabinofuranosyladenine [152, 154], The evidence for the incorporation of 9-(3-D-arabinofuranosyladenine has been questioned [345]. 

Enzymic discriminations of enantiopic groups of weso-compounds have been widely exploited in asymmetric synthesis. Ohno and co-workers reported a total synthesis of L- and D-ribose, showdomycin and cordycepin based on the optically active half-esters 56 and 57, which were obtained enzymatically (Pig Liver Esterase PLE) from the corresponding mcso-diesters 54 and 55, respectively, derived from the Diels-Alder adduct 53 of furan to dimethyl acetylenedicar-boxylate. The diesters 58 - 60 were also found to be good substrates for PLE leading to the corresponding half-esters 61 - 63 with high enantiomeric purities. ... 

Many antibiotics produced by various microorganisms are nucleosides (2). Among these are nebularine, cordycepin, and nucleocidin. The only known purines in higher plants shown to be involved In allelopathy are caffeine, theophylline, paraxanthine, and theobromine from the coffee tree... 

Asymmetric synthesis of stavudine and cordycepin, anti-HIV agents, and several 3 -amino-3 -deoxy-P-nudeosides was achieved utilizing this cycloisomerization of 3-butynols to dihydrofuran derivatives [16]. For example, Mo(CO)6-TMNO-promoted cyclization of the optically active alkynyl alcohol 42, prepared utilizing Sharpless asymmetric epoxidation, afforded dihydrofuran 43 in good yield. Iodine-mediated introduction of a thymine moiety followed by dehydroiodination and hydrolysis of the pivaloate gave stavudine in only six steps starting from allyl alcohol (Scheme 5.13). 

Cordyceps sinensis Link. Dong Chong Xia Chao (fruit body) 2 -deoxyadenosine, adenosine, sterols, saccharides, protein, cordycepin, d- mannitol 33,91,92,401,402,412,413,414,459 Lead poisoning was reported.238 Antisenescence, hypolipidemic, endocrine, antitumor, antiatherosclerotic and sexual function-restorative activities. Treat respiratory, renal, liver and cardiovascular diseases, antileukemic cells, hyposexuality, and hyperlipidemia. 

---