2′-deoxy-3,7-dideazaguanosine and related compounds. Synthesis of 6-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl) and 1-β-D-arabinofuranosyl-1H-pyrrolo[3,2-c]pyridin-4(5H)-one via direct glycosylation of a pyrrole precursor

Open Access
Publisher Website
Google Scholar
Abstract
The synthesis of two new analogs of 2′-deoxyguanosine, 6-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (8) and 6-amino-1-β-D-arabinofuranosyl-1H-pyrrolo[3,2-c]-pyridin-4(5H)-one (13) has been accomplished by glycosylation of the sodium salt of ethyl 2-cyanoaethyl-1H-pyrrole-3-carboxylate (4c) using 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranose (5) and 1-chloro-2,3,5-tri-O-benzyl-α-D-arabinofuranose (9), respectively. The resulting blocked nucleosides, ethyl 2-cyanomethyl-1-(2-deoxy-3,5-di-0-p-toluoyl-β-D-erythro-pentofuranosyl)-1H-pyrrole-3-carbox-ylate (6) and ethyl 2-cyanomethyl-l-(2,3,5-tri-0-benzyl-β-D-arabinofuran-osyl)-1H-pyrrole-3-carboxylate (10), were ring closed with hydrazine to form 5-amino-6-hydrazino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-1H-pyrrolo[3,2-c]-pyridin-4(5H)-one (7) and 5,6-diamino-1-(2,3,5-tri-0-benzyl-β-D-arabino-furanosyl)-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (11), respectively. Treatment of 7 with Raney nickel provided the 2′-deoxyguanosine analog 8 while reaction of 11 with Raney nickel followed by palladium hydroxide/cyclohexene treatment gave the 2′-deoxyguanosine analog 13. The anomeric configuration of 8 was assigned as β by proton NHR, while that of 13 was confirmed as β by single-crystal X-ray analysis of the deblocked precursor ethyl 2-cyanomethyl-1-β-D-arabinofuranosyl-1H-pyrrole-3-carboxylate (10a).