Purine leaving groups

Imidazole can be A -allylated. The A -glycosylimidazole 299 is prepared by regiospecific amination at the anomeric center with retention of configuration. Phenoxy is a good leaving group in this reaction[181]. Heterocyclic amines such as the purine base 300 are easily allylatedfl 82]. 

Because aromatic purines and purine nucleosides and free purines such as hypo-xanthine and guanine 242 are readily silylated-aminated [64] (cf Scheme 4.24), it is obvious that 6-membered hydroxy-N-heterocycles are analogously silylated-aminated, with reactivity in the order given in Scheme 4.25 [73] X=OTf is the best leaving group and X=NHSiMe3 (cf the transamination as discussed in Section 4.2.4) is the weakest. 

An interesting synthetic approach has been used in the synthesis of adenosine analogs. Rodenko et al.27 generated a leaving group at C2 of 6-chloropurinylribofuranoside (34) via electrophilic nitration (Fig. 6). The replacement 6-chloro function was very facile in the electron-poor purine... 

To introduce a (S-fluoro group at the C-2 position of a ribonucleoside, one may first try an Sn2 reaction of a fluoride ion with a 2 -hydroxyl group activated as a leaving group, such as triflate. However, in most cases, its nucleobase (both pyrimidine and purine) prevents this reaction because (a) steric hindrance of the nucleobase interrupts the nucleophilic (F-) attack from the top face, and (b) the nucleobase reacts intramolecularly with its own sugar moiety. Therefore, 2 -P-fluoro substitution is generally more difficult than the corresponding a-fluoro substitution. 

A vej atile procedure for the introduction of alkyl, epoxyalkyl groups into heterocycles, which Involves displacement of leaving groups by Wittig reagents, followed by appropriate manipulation of the resulting ylides, has been applied to the synthesis of various 6-substl ted purines designed as inhibitors of adenylsuccinate synthetase and lyase. 

Figure 9.13. hPNP-catalyzed phosphorolysis of the purine nucleoside. The guanine leaving group and phosphate nucleophile are /ell separated from the oxacarbenium ion, defining a very dissociative TS. 

A device that is also used in pyridine and purine chemistry is the initial replacement of halogen with a tertiary amine the resulting salt, now having a better leaving group, undergoes nucleophilic substitution... 

Other useful leaving groups in purine chemistry inclnde sulfoxide,triflate, and aryl- or alkylthio. Sulfones are highly reactive in some nucleophilic substimtions, and are also the reactive intermediates in sulfinate-catalysed displacements of halide. ... 

These reactions, involving nucleophilic displacement of other halogens by fluoride anion are important industrially and of some use in the laboratory for electron-deficient rings. The exchange/equilibrium of with is of use in PET (see 31.2.3). Nitro is also a good leaving group for this process in a number of systems purines (27.5), pyridines (8.3.2) and 1,2,4-triazoles (29.1.1.2). 

The substrates can be halides, but nitro and quaternary ammonium are the preferred leaving groups in azines and purines." Such reactions are standard, but apparently un-activated substrates, such as the nitro-oxindole shown below, have also been used successfully.""... 

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