3 -amino-3 -deoxyadenosine

Amino-3 -deoxyadenosine. 3 -Amino-3 -deoxyadenosine (17) is elaborated by Cordyceps militarise Aspergillus nidulanSe and Helminthosporium (3,4). The biosynthesis proceeds direcdy from adenosine. Compound (17) inhibits RNA polymerase, but not DNA polymerase, and replaces the adenosyl residue at the 3 -terminus of tRNA. Phenylalanyl-(3 -amino-3 -deoxyadenosyl)-tRNA has acceptor but not donor activity (31,32). Compound (17) also inhibits retroviral RNA-dependent DNA polymerase (33). 

A cyclic nucleotide, 2, 3 -bis(2-chloroethyl)aminophosphoryl-3 -amino-3 -deoxyadenosine (139) showing antitumor activity, was prepared in 40% yield starting from 3 -amino-3 -deoxyadenosine 133 by its phosphorylation with N,N-bis-(2-chloroethyl) amidophosphoryl dichloride 138. Both P-diastcrcomers separated by column chromatography exhibit activity against KB tumor cell cultures (Scheme 40) [71]. 

Scheme 40 Synthesis of 2 ,3 -bis(2-chloroethyl)aminophosphoryl-3 -amino-3 - deoxyadenosine 139...

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 mechanism of inhibition of these protozoal infections by the most active drugs, puromycin and the aminonucleoside, is not known. Puromycin and nucleocidin both interfere with protein synthesis, but the aminonucleoside does not. It is known to be demethylated to 3 -amino-3-deoxyadenosine, which is phosphorylated and interferes with nucleic acid metabolism (see above). Whether puromycin must be converted to the aminonucleoside before it can inhibit protozoa has not been established. Some purine analogues known to interfere with nucleic acid metabolism, however, are less effective as antiprotozoal agents, even in vitro, perhaps because their effects are primarily on the de novo pathway which many, if not all, protozoa do not use [406]. 

Because of their basicity (lower than that of aliphatic amines), aromatic primary amines can be selectively nitrosated179 in the presence of aliphatic amines at low pH. An example is provided by the deamination of 3 -amino-3 -deoxyadenosine, although the yield of the product isolated, 3 -amino-3 -deoxyinosine, was180 only about 4%. Some 50% of the starting material remained unchanged, and hydrolysis released adenine (30%). 

AMDOAD. o-D-2 -Amino-2 -deoxyadenosine monohydrate (C10H14N6O3, H20). Rohrer DC, Sundaralingam M (1970) J Am Chem Soc 92 4956 AMQADA. 3 -Amino-3 -deoxyadenosine (C10H14N6O3). Sheldrick WS, Morr M (1980) Acta Crystallogr, Sect B 36 2328... 

U-14C]adenosine — incorporation into 3 -amino-3 -deoxyadenosine without cleavage of the ribosyl carbon-nitrogen bond856... 

Amino-3 -deoxyadenosine (plus 3 -N-acetylhomocitrullyl and lysyl) (Helminthosporium, Cordyceps militaris and Aspergillus nidulans) B-70MI40900, p. 176... 

That the success of these chloromercuri condensation reactions is dependent on the purine as well as on the glycosyl halide used was recognized as a result of work on the preparation of 3-amino-3-deoxyadenosine (66a).In this case, reaction of the chloromercuri derivative of iV -benz-oyladenine (65a) with the titanium chloride complex (56) gave a 3 1 mixture of (8 and a anomers (66a and 67a). The a-D anomer may result from anomerization of the /8-d anomer initially formed. When the chloromercuri derivative (65a) was allowed to react with the 2,5-di-O-benzoyl-3-deoxy-3-phthalimido-n-ribofuranosyl chloride (62), no a-o anomer was observed and, since no 7-isomer was encountered either, this... 

Novel cyclic di- and triphosphate derivatives of 3 -amino-3 -deoxyadenosine-5 -diphosphate (75) and triphosphate (76) have been prepared " by cyclisation of the respective 5 -di- and triphosphate derivatives of 3 -A -Boc-3 -amino-3 -deoxyadenosine using the water-soluble carbodiimide 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), followed by removal of the Boc protecting group with TFA. The acyclic polyphosphate precursors were prepared according to Yoshikawa and Ludwig after first dissolving the nucleoside in hot triethylphosphate. The reaction proceeds via the intermediacy of the 5 -phosphorodichloridate derivative, partial hydrolysis of which gives the monophosphate, whilst traces of pyrophosphoryl chloride result in... 

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-... 

PAN was demethylated and phosphorylated to the 5 -nucleotide of 6-methyl-amino-9-(3 -amino-3 deoxyribofuranosyl)purine. In vitro, an additional metabolite of PAN was fonaed via a second demethyTatim to form the nucleoside, 3 -amino-3 -deoxyadenosine. 

Amino-3 -deoxyadenosine a purine antibiotic synthesized by Cordyceps militaris and Helmintho-sporium species (see Nudeoside antibiotics). It has antitumor activity. The acetylated derivative, 3 -acet-amido-3 -deoxyadenosine, has also been isolated ftom Helminthosporium species... 

Amino- 3 -deoxyadenosine Cordyceps militaris, Helminthosporium spp. Adenine 3-Amino- 3-deoxyribose Adenosine... 

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... 

---