Cordycepin phosphate

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. 

The majority of newly reported nucleoside 5 -monophosphates have been prepared using phosphorus oxychloride in trialkyl phosphate solution. These include the monophosphates of 2-fluoroadenosine, 2-amino-6-chloro-9-(/S-D-ribofuranosyl)-purine, bredinin (6), cordycepin 2 -azido-2 -deoxyadenosine, 2 -fluoro-... 

Figure 1-3 shows a number of nucleoside antibiotics which contain adenine and an unusual sugar at the 9-position. Cordycepin (3 -deoxy-adenosine) is a cytostatic agent and is converted to the 5 -mono-, di-, and triphosphate derivatives in mouse tumor cells. Cordyceps militaris, the organism which produces cordycepin, also produces a related analogue with antitumor activity, 3 -amino-3 -deoxyadenosine this compound is also metabolized by way of phosphate derivatives. The angustmycins, psicofuranine and decoyinine, are, respectively, the 9-j3-D-psicofuranosyl... 

Azacytidine 2, 3, 5 -Tri-Ac, A-887 6-Azacytidine 2, 3, 5 -Tribenzoyl, A-887 6-Azacytidine, A-887 8-Azaguanosine 5 -Phosphate, A-888 6-Azathymidine 3, 5 -Diphosphate, A-891 6-Azathymidine 3 -Phosphate, A-891 6-Azathymidine 5 -Phosphate, A-891 8-Azidocyclic AMP, A-897 3 -Azido-3 -deoxy-5 -thymidylic acid, 9CI, Z-4 Benzyl 2-amino-4,6-0-benzylidene-2-deoxy-a-D-glucopyranoside 3-(dihydrogen phosphate), A-272 8-Bromocyclic AMP, B-53 8-Bromocyclic GMP, B-54 Bucladesine, INN, C-162 Bucladesine sodium, JAN, C-162 Coenzyme A, C-144 Coenzyme II, C-145 Coenzyme I, C-143 Cordycepin 5 -Triphosphate, C-152 Cyclic ADP-ribose, C-I6I Cyclic AMP A-Butanoyl, C-162 Cyclic AMP 2 -Deoxy, C-162 Cyclic AMP, C-162 Cyclic CMP, C-163 Cyclic GMP, C-164 Cyclic TMP, C-165 Cyclic UMP, C-166... 

Syntheses of the adenosine and guanosine 5 -phosphoroazidates (622) and (613), which were required as affinity labels, of P -di([ C]adenosine-5 )penta-phosphate, an inhibitor of adenylate kinase (E.C. 2.7.4.3), and, by improved procedures, of 3 -deoxyadenosine (cordycepin) 5 -triphosphate have been reported. 2 -Deoxy-2 -deuterio-adenosine (276) (see p. 100) and its 2 -epimer have been converted into the corresponding 3, 5 -phosphates, whose conformers were examined by H n.m.r. spectroscopy." ... 

A prumycin analogue is referred to in Chapter 9, and dinucleoside phosphates containing AZT and cordycepin constituents are mentioned in Chapter 20. 

The 3, 8-5 -anhydronucIeoside (489) has been converted into the corresponding 2, 5 -phosphate, which gave 9-(3-deoxy-j8-D-er> tAro-pentofuranosyl)adenine (cordycepin) 2, 5 -phosphate (490) on desulphurization with Raney nickel.An improved synthesis of /3-hydroxyethyl esters of nucleoside 5 -phosphates was... 

U- C is the direct precursor. Cordycepin-U- H is not a direct precursor for 3 -amino-3 -deoxyadenosine. Therefore, adenosine or its 5 -phosphate is the precursor for 3 -deoxyadenosine and 3 -amino-3 -deoxyadenosine. Since these two nucleosides are structurally related, it may be that adenosine is converted to a compound that is a common precursor. 

Matsushima, K., and F. J. Simpson The purification and properties of D-allose-phosphate isomerase of Aerohacter aerogenes. Can. J. Microbiol. 12, 313 (1966). SuHADOLNiK, R. J., and J. G. Cora Further evidence for the biosynthesis of cordycepin and proof of the structure of 3-deoxyribose. Biochim. et Biophys. Acta 91, 661 (1964 a). 

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