3 -Amino-3 -deoxyadenosine, phosphate

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. 

A phosphorylase from Escherichia coli has been purified it is specific for 2-deoxy-D-ribosyl phosphate, but can use uracil, 2-thiouracil, 5-amino-uracil, 5-bromouracil, and 2-thiothymine as a pyrimidine. Deaminases of adenosine, 2-deoxyadenosine, cytidine, and 2-deoxycytidine have been detected in Escherichia coli. 

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-... 

Syntheses involving standard condensation procedures for heterocyclic bases with amino-sugar derivatives have included the preparation of 2 -azido-, 3 -azido-2 ,5 -diazido-, and 3, 5-diazido-derivatives of arabino-nnAinc, 3 -amino-3-deoxy-adenosine, -uridine, and -cytidine 5-phosphates, 2, 3-bis(2-chloroethyl)-aminophosphoryl-3-amino-3-deoxyadenosine (which has anti-tumour activity), 3-A -methyl-A -nitrosoureido-3-deoxy-adenosine and the corresponding 5-substituted isomer, and 2 -azido-2-deoxy- and 2-amino-2-deoxy-D-arabinofuranosyl-... 

The aspect of a reversible reaction of fluorinase was of major importance for further optimizations and by addition of the enzyme L-amino acid oxidase (L-AAO) the oxidative removal of formed L-methionine was enabled. In this way, the equilibrium of the reaction was pulled toward 5 -[ F]FDA and allowed very high radiochemical yields of 95% within 1-2 h. Accordingly, the F-labeled compounds 5 -[ F]fluoro-5 -deoxyinosine (5 -[ F]FDI) (O Fig. 42.30h), 5 -[ F]fluoro-5 -deoxyribose phosphate (O Fig. 42.30c)y and 5 -[ F]fluoro-5 -deoxyribose (O Fig. 42.30d) were successfully produced from 5 -[ F]fluoro-5 -deoxyadenosine (Deng et al. 2006, Onega et al 2009, 2010). In the base-swap strategy, the 5 [i F]fluoro-5 -deoxyribose phosphate O Fig. 42.30c) could be further transformed into... 

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... 

Then the 7,8-diaminononanoate (7,8-diaminopelargonic acid) (Scheme 12.93) is converted to the bisamide dethiobiotin (an imidazolidone) by carboxylation with carbon dioxide (CO2) in the presence of ATP in a reaction requiring magnesium (Mg+ ) and catalyzed by dethiobiotin synthase (EC 6.3.3.3). The well-known reversible reaction of amines with carbon dioxide (CO2) and an X-ray crystal structure showing the 8-amino group as a mixed carbonic phosphate anhydride has lent support to this picture (PDB la82). Finally, in the presence of biotin synthase (EC 2.8.1.6), an enzyme that appears to be used only once in each synthesis, reaction occurs with 2 equivalents (but almost certainly one at a time) of SAM and sulfur to produce biotin, 2 equivalents of methionine (Met, M), and 2 equivalents of 5 -deoxyadenosine. 

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. 

---