The nucleoside antibiotic ascamycin [2-chloro-5'-g-[I+(k-alanyljsulfamoyl) adenosine (l)] has been synthesized by an improved procedure involving the direct condensation of 2-chloro-2',3'-~-isopropylidene-5'-~-sulfamoyladenosine (3) with Bock-Ala-O% in DMF and in the presence of DBU. followed by removal of the protecting groups. A similar condensation of p with Boc-t-Ala-OSu and Boc-Gly-OSu, and subsequent deprotection, yielded the E-Ala and Gly analogues of 1, namely 2-chloro-5'-0-[N-CDalanyl)sulfamoyl]and 2-chloro-5'-0-[N-(glycyl)sulfamoyl]adenosine [D-ascamycin ( 14) and (1811. Similar reactions of 2'; ,3T-0-isopropylidene-5'-O-sulfamo~ladenosine, E', with the three amino acidderivatives above mentioned provided the corresponding abnosine analogues 12, 16 and 20. Several studies directed to demonstrate that the previous protection of the 6-NH2 group of the adenosine derivatives 2 and 2 is not necessary for the selective aminoacylation of the S02NH2 group are also reported. Ascamycin (1) is a new nucleoside antibiotic recently isolated from a fermentation broth of Streptomyces'. It shows a remarkably selective antibacterial activity as compared to dealanylascamycin [the antibiotic AT-2652,(2)3]. This selectivity in the case of Xanthomonas citri is due to a dealanylating enzyme present in the bacterial surface which, by removing the alanyl residue, affords dealanylascamycin and facilitates the selective uptake of this nucleoside derivative.
A synthesis of 1 has been reported by Isono et al 495 which involves condensation of N6-benzyliz oxycarbonyl (Z) or N -tert-butyloxycarbonyl(Boc)-2-chloro-2' ,3'-g-isopropylidene-5'-c-sulfamoyl-