Branched-chain N-sugar nucleosides : Part III. α- and β-nucleosides of branched-chain 3- C-(cyanomethyl)-, 3- C-(2-aminoethyl)-, and 3- C-( N,N-dimethylcarbamoylmethyl)-2,3- dideoxy- D- ribo-hexopyranoses

Abstract

Condensation of diethyl (cyanomethyl)phosphonate with methyl 4,6- O-benzylidene-2-deoxy-α- D- erythro-hexopyranosid-3-ulose ( 1) by a Wittig reaction afforded, after chromatographic separation, ( E)- and ( Z)-methyl 4,6- O-benzylidene-3- C-(cyanomethylene)-2,3-dideoxy-α- D- erythro-hexopyranoside ( 2 and 3) in 69 and 7% yields, respectively. Stereospecific, catalytic reduction of 2 or 3 yielded methyl 4,6- O-benzylidene-3- C-(cyanomethyl)-2,3-dideoxy-α- D- ribo-hexopyranoside ( 4). Compound 2 was selectively debenzylidenated with Dowex 50W X-8 to produce 5. Under the same conditions, saturated compound 4 underwent debenzylidenation and anomerization to afford the α,β-mixture 7. The latter product was ( p-chlorobenzoyl)ated, and the mixture then separated to yield pure α anomer 8 and impure compound 9. Fusion of the α anomer 8 with 2,6-dichloropurine afforded, after chromatography, 2,6-dichloro-9-[4,6-di- O-( p-chlorobenzoyl)-3- C-(cyanomethyl)-2,3-dideoxy-α- D- ribo-hexopyranosyl]purine ( 11) and the β anomer 12 in 37 and 24% yields, respectively. Treatment of the α anomer 11 with aqueous methanolic dimethylamine yielded 2-chloro-9-[2,3-dideoxy-3- C-( N,N-dimethylaminocarbamoylmethyl)-α- D- ribo-hexopyranosyl]-6-( N,N-dimethylamino)purine ( 14) in 54% yield. Similar treatment of the β anomer 12 gave the corresponding, unprotected nueleoside 16, which still possessed the cyanomethyl group. The unprotected, branched-chain cyano-nucleoside 15 was converted into the corresponding amino sugar nucleoside, namely, 9-[3- C-(2-acetamidoethyl)-2,3-dideoxy-α- D- ribo-hexopyranosyl]-2,6-di-( N,N-dimethylamino)purine( 17).