A facile synthesis of ascamycin and related analogues

Abstract

The nucleoside antibiotic ascamycin [2-chloro-5'- O -[ N -( L-alanyl )sulfamoyl] adenosine 1 ] has been synthesized by an improved procedure involving the direct condensation of 2-chloro-2',3'- O -isopropylidene-5'- O -sulfamoyladenosine ( 3 ) with Boc- L -Ala-OSu in DMF and in the presence of DBU, followed by removal of the protecting groups. A similar condensation of 3 with Boc- D -Ala-OSu and Boc-Gly-OSu, and subsequent deprotection, yielded the D -Ala and Gly analogues of 1 , namely 2-chloro-5'- O -[ N -( D -alanyl)sulfamoyl] and 2-chloro-5'- O -[ N -(glycyl)sulfamoyl]adenosine [ D -ascamycin ( 14 ) and (18)]. Similar reactions of 2',3'- O -isopropylidene-5'- O -sulfamoyladenosine, 6 with the three amino acid derivatives above mentioned provided the corresponding adenosine analogues 12 , 16 and 20 . Several studies directed to demonstrate that the previous protection of the 6-NH 2 group of the adenosine derivatives 3 and 6 is not necessary for the selective aminoacylation of the SO 2NH 2 group are also reported.