Synthesis and some transformations of 2-acetamido-5-amino-3,4,6-tri-O-benzyl-2,5-dideoxy-D-glucono-1,5-lactam

摘要

The lactam 21 was obtained in an overall yield of 72% from the hydroxy amide 16 by oxidation with the Dess-Martin periodinane, acid-catalysed isomerization of the oxidation products in toluene, whereupon 18/19 precipitated, and reductive dehydroxylation of 18/19 (Et3SiH/BF3 . OEt2; Scheme f). The amide 16 was obtained by ammonolysis of the N-acetylglucosamine-derived lactone 15. Depending on the oxidation method, 16 yielded the keto amide 17, the hydroxy lactams 18/19, and the pyrrolidinecarboxamide 20 in widely different proportions. The pyrrolidinecarboxamide 20 was not reduced under the conditions of the reductive dehydroxylation. Hydrogenolysis of the benzyl-protected lactam 21 gave the trihydroxy lactam 22, while reduction with NaBH4/BF3 . OEt2 led to the 2-acetamidopiperidine derivative 24 (Scheme 2). Selective (tert-butoxy)carbonylation of the lactam 21 (--> 25) followed by NaBH4 reduction and acid-catalysed solvolysis in EtOH led to the alpha-ethoxycarbamates 28/29. Similarly, (tert-butoxy)carbonylation of 1 (--> 31) followed by reduction to 32/33 and glycosidation yielded the ethoxycarbamate 34. Treatment of the GlcNAc-derived ethyl glycosides 28/29 with Me3SiCN/BF3 . OEt2 gave the equatorial amino nitrile 30. Under similar conditions, the Glc-derived glycoside 34 led to the iminooxazolidinone 35. In the presence of a larger proportion of Me3SiCN at 5 degrees, 34 was transformed into the axial, selectively monodebenzylated amino nitrile 36. [References: 54]