6-chloropurine ribosides

The general scheme for preparation of the alkylated adenosine and deoxyadenosine involved the interaction of the appropriate amino-hydrocarbon with a 6-chloropurine riboside (116). This allowed for the most specific interaction without too many byproducts. The molecular structures determined from diffraction studies are shown in Figures 24 and 25. In Figure 24 the shape of an alkylated nucleoside (115) is compared with that of the unalkylated form,... 

Tetrahydropyran-2-yl (THP)-protected 6-chloropurine l32 and bis(THP)-protected 2-amino-6-chloropurine 2,33 as well as 2, 3, 5 () (riacetyl 6-chloropurine riboside 334 and its 2 amino 6 chloropurine analogue 435 were chosen as suitable starting compounds for the cross coupling reactions with unsubstituted and fluorinated phenylboronic acids 5a—d. Due to the lability of the... 

Similarly, adenosine, inosine and 2 -deoxyinosine have been converted into their 8-trifluoromethyl derivatives by reaction with the copper complex formed from trifluoromethyl iodide and copper in hexamethylphosphorotriamide (80JCS(P1)2755). iV -Trifluoromethyl-purine riboside was also produced from 6-chloropurine riboside. Recently, guanosine has been shown to give the C (8)-substituted derivative (148) by reaction with a benz[a]anthracene 5,6-dioxide at pH 9.5 over 4 days at 37 °C (80CC82). 

In this section, we describe the industrial synthesis of FddA starting with 6-chloropurine riboside, which is readily available from inosine. 

In this way, we obtained FddA via F-ara-A (42) in a fairly good overall yield from 6-chloropurine riboside. However, to establish a scalable process, each reaction step must be improved and further investigations are needed to optimize conditions for fluorination and deoxygenation on an industrial scale. 

In a similar way the treatment of V -cinnamylidenesul-fanilamide (prepared from cinnamic aldehyde and sulfanyl-amide) with sodium bisulfite affords noprylsulfamide (Fig. 36.10), according to the soluseptazine principle (noprylsulfamide is also called soluseptazine). Noprylsulfamide is freely soluble in water (200 g 1 ), and breaks down in the body with the liberation of free sulfanilamide. Treatment of 6-chloropurine riboside with p-aminobenze-nesulfonic acid leads to the highly water-soluble N -(p-... 

After selective lithiation at C-8 in a 6-chloropurine riboside, quench with a stannyl or silyl chloride leads to the isolation of the 2-substituted compound, via rearrangement of a 2-anion formed by a second lithiation of the initial 8-substituted product, as illustrated below. ... 

Figure 3 illustrates the synthesis of the 2 -0-allyladenosine monomer, 16. The starting material, 11, is prepared from 6-chloropurine riboside in two steps, as previously described (12,15). Allylation as described above affords compound 12 in 79% yield. Displacement of the 2,6-dichlorophenoxide by ammonia is rather slow and takes 7 d at 95 C in a bomb however, the conversion of compound 12 to the intermediate 3, 5 -0-(tetraisopropyldisiloxane-1,3-diyl)-2 -0-allylade-nosine is very clean. Pivaloylation affords compound 13 in moderate yield. Subsequent desilylation, dimethoxytritylation, and phospitylation each go in over 90% yield to give the desired 2 -0-allyladenosine monomer, 16. 

Casu et al. reported the synthesis of 2 -substituted inosine analogues (27) by masking the 6-hydroxyl group. The corresponding analogues were prepared from 6-chloropurine riboside via 6-dimethylaminopurine or 6-benzyloxypurine intermediates. 

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