The synthesis of acyclic analogues of ribo-and deoxyribonucleosides is described. These compounds (Table ) are both poor substrates and poor inhibitors of adenosine deaminase. The synthesis of dinucleotides from these analogues is also described, and the activity along with the inhibitory properties of some of them are studied against deaminase enzyme. These nucleotides are resistant to degradation by phosphodiesterases. HC1 impregnated on silica gel is an excellent reagent for the preparation of the chloromethyl ether precursors of acyclo-nucleosides. A general and rapid procedure is developed for the preparation and isolation of the 5'-aminoacyl derivatives of ribo-and arabinonucleosides. Quinoline has a marked effect on aminoacylations without racemization. Compounds 35a, b possess remarkable antiviral effects in v i m . A procedure is also developed for the conversion of acyclo-ribonucleosides 13e, f to acyclo-deoxyribonucleosides 1 le, f. HELVETICA CHIMICA ACTA -Val. 70 (1987) Rxlo ZC'
y.ORyAde 2. R=CI. R ' = H. R ' = H 3s R=Cl. R' =H. R * = ti b R = CI. R' = CH,CI. R' = H c R=OBz.R'=H.R'=H d R=OBz. R'=CH(OBz)CH20BZ. R1=H(ZRS.3SR) e R=OBz. R' =CH(OBZI)CH~OBz. R2=H(2R.3R) f R=OBr. R'=CH(OBzI)CH20BZ, R2=H(2S,3S) c'R=OBz. R'=H, R'=COOMe b R = CI. R' = Ch, CI. R'= H f R =OBI. R ' = H. R'= H d R=OBz. R'=CH(OBr)CH,0B~.Ri=H(ZRS,3SR) e R=OBz. R' =CH(OBzI)CH,OBz. R2=H(ZR,3R) f R = O B z . R'=CH(OBzI)CH,OBz. R 2 = H ( Z S , 3 S ) c' R = 081. R' = H, R' = COOMs Bz = PhCO, Bzl = PhCH,, Ade = Adenin-9-yl
same perspective, HCl in aq. solution can be adsorbed on silica gel and then converts alcohols in aprotic solvents to the corresponding chloromethyl ethers in the presence of aldehydes.
Addition of silica gel (Merck, act. 1) to conc. aq. HCI (37 %) and refluxing the mixture for a few hours affords a white granular material (see Exper. Part). Titration of the HCI impregnated on silica gel reveals, even after two months, that the reagent activity does not vary appreciably with time. The reaction rate of 1+2 is, apparently, dependent both on the structure of the alcohol and on the ratio substrates/HCl. However, with 2 g of HCl/silica gel per 1 mmol of each substrate, the reaction is complete within 24 h at 25". It may be carried out in solvents such as EtzO or CHCI, without any considerable effect in yield.