3’,5’-Protected adenosine derivative

Hladezuk et al. developed rhodium catalysed O-H insertion reactions (shown in Scheme 4) using a-diazophosphonates reacting with uridine, thymidine and protected adenosine derivatives for the preparation of... 

N-Acyl derivatives (lb. Id, le, If, Ig, Ih, Ij, Im and lo) were prepared from either the protected adenosine 3, or its chloro analogue, by standard procedures (Scheme 2). N-alkyl derivatives (li, Ik, 11 and In) were prepared by the base mediated alkylation of compound 4 followed by acid catalysed deprotection, e.g. compound li was prepared from compound 4 in a 22% overall yield. Dealanylascamycin la was prepared by the hydrolysis of the chloro analogue of compound 4. ... 

Zhao has reported the preparation of alkyl thiophosphoramidate derivatives of 2, 3 -protected adenosine (21a-d) and uracyl (22a-d) starting from 0-isopropyl phosphorodichloridothioate. The key step was the coupling of the protected nucleosides with alkyl methoxyaminoacyl thiophosphorochloridate in the presence of triethylamine. ... 

It was found recently that 2, 3 -0,0-protected adenosine and similar derivatives could be efficiently phosphorylated under Mitsunobu conditions when the reaction was carried out in anhydrous pyridine. Less nucleophilic phosphonates also reacted, but gave lower yields [114]. The use of nucleosides non-protected at the 2 and 3 positions led to the formation of by-products, and 5 -phospho-rylated adenosine or derivatives could not be isolated satisfactorily. 

Routes to 8-fluoropurines had been limited until recently. However, an efficient one-step synthesis was reported in 1996 that has made available these compounds for a variety of studies. Thus, reaction of a series of protected oxopurines and protected adenosine with 1% F2 in He gave the corresponding 8-fluoro derivatives in 25-30% yields (Fig. 3.60). 2, 3, 5 -Tri-0-acetyl-8-fluoroadenosine so prepared was found to undergo defluorination under normal conditions of deprotection. A thermal labile hydrolase was subsequently used to effect this deprotection to produce, for the first time, free 8-fluoroadenosine. More detailed studies on the mechanism of defluorination of 8-fluoropurines indicated that acidic conditions are incompatible with 8-fluoroguanine and 8-fluoroadenosine while basic conditions are also incompatible... 

At a higher temperature, a mixture of diastereomers was obtained. The protected adenosine (B = adenosine) derivative also undergoes a smooth reaction, affording the analogous phosphonate in 82% yield. 

In a study on the reaction of arenesulfenyl chlorides with hydroxyl functions of ribonudeosides, the Pmoc residue was employed as a protective group for the 5 -hydroxy function in an adenosine derivative [628]. Reaction of 864 with Fmoc-Cl afforded the 5 -0-Fmoc-adenosine derivative 865 in 82% yield. 

One of the better processes for the conversion of adenine to adenosine involves the initial conversion of adenine to the corresponding N -benzoyl derivative with benzoyl chloride in pyridine. Then, as shown in Scheme 12.100, silylation with trimethylchlorosilane in hexamethyldisilazane [(CH3)3Si]2NH solvent at reflux yielded a silyl derivative that was heated in 1,2-dichloroethane (CICH2CH2CI) at reflux with trimethylsilyl perchlorate [(0113)3810104] and l-0-acetyl-23,5-tri-0-benzoyl-P-D-ribofuranose for 12 h. The resulting crude, protected adenosine was converted to unprotected material by standing at room temperature with methano-lic ammonia followed by recrystaflization from aqueous methanol. 

A synthesis of 2 -0-methyluridine has been carried out by a procedure in which the 3, 5 -0-TIPDS derivative of uridine was protected at N-3 by the p-methoxybenzyl group,208 and the "wobble position" nucleoside 2 -0-methyl-5-(methoxycarboxylmethyl)uridine has also been prepared by similar means.209 The 2 -0-allyl derivative (141) of uridine is accessible by a palladium-catalysed decarboxylation of (142), and a similar reaction is possible on an adenosine derivative.210 2 -0-Propargyl uridine can be prepared via the 2, 3 -0-dibutylstannylene derivative the triple bond of this derivative could then be converted into an unusual carboranyl group, the resultant structure being of potential use in the neutron capture therapy of cancer.211 A conference report has discussed the use of 2-(methylthio)-phenylthiomethyl (MPTM) ethers for protection of the 2 -hydroxyl group in oligoribonucleotide synthesis.212... 

An interest in ester migration in the monoacyl derivatives of the vicinal-diol grouping in ribofuranosides stemmed from a desire to establish the position of attachment of the aminoacyl group to the terminal adenosine residue of aminoacyl-(t-RNA),569-571 and also from the necessity of producing suitably protected intermediates for oligoribonucleotide syntheses. That a facile equilibrium can exist is shown by the fact that, on being kept, an ethanol solution of... 

Clarke H, Cushley MJ, Persson CG, Holgate ST (1989) The protective effects of intravenous theophylline and enprofylline against histamine- and adenosine 50-monophosphate-provoked bronchoconstriction implications for the mechanisms of action of xanthine derivatives in asthma. Pulm Pharmacol 2(3) 147-154... 

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