2-Aminonucleosides synthesis

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]. 

Aminonucleosides can offer interesting physiological properties. Some routes for the synthesis of new analogs of this kind of compounds have been described [26] A modified route for the preparation of 3, 5 -diamino-3",5 -trideoxythymidine is outlined in Scheme 10.10. The reaction, which takes place in four steps with an overall yield of 63%, is an improvement on the earlier described process [27]. 

CouTSOGEORGOPOULOS, C., Amino acyl-aminonucleoside inhibitors of protein synthesis. The effects of amino acyl ribonucleic add on the inhibition. Biochemistry 1967, 6, 1704-1711. 

A full account has been given of the synthesis of cordycepin via a furanoid glycal intermediate (Vol. 29, p. 258), and a similar approach has been adopted for the synthesis of the puromycin aminonucleoside (25), as outlined in Scheme 1 ... 

A paper on the total synthesis of spicamycin aminonucleoside is mentioned in Chapter 10. 

Recently, a stepwise synthesis of acetamidate-bridged oligonucleotides has been published by Nyilas et al. (26). They used the 5 -azido-compounds as 5 -aminonucleoside synthons (Fig. 13). 3 -0-carboxymethylation is carried out with sodium chloroacetate in the presence of NaH at 20°C. 5 -Azido-5 -deoxythymidine does not need to be protected, for the other bases, the monomethoxytrityl protection... 

However, 4-N-glycylspicamycin aminonucleoside (SAN-Gly), which has no fatty acid chain and is thought be generated from KRN5500 by a c 4osomal enzyme, has exhibited a marked inhibitory effect on protein synthesis in the cell-free system. Nevertheless, SAN-Gly has shown 1000-fold weaker cytotoxicity than KRN5500 in vitro because of its poor intracellular incorporation". Therefore, to obtain an antitumor effect in vivo KRN5500 should be administered intravenously. Since it is insoluble in... 

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