Synthesis and immunoadjuvant activity of N-[2-O-(2-acetamido-1,2,3,5-tetradeoxy-1,5-imino-d-glucitol-3-yl)-d-lactoyl]-l-alanyl-d-isoglutamine

✍ Scribed by Hideharu Ishida; Masayuki Kitagawa; Makoto Kiso; Akira Hasegawa; Ichiro Azuma

• Publisher: Elsevier Science
• Year: 1990
• Tongue: English
• Weight: 416 KB
• Volume: 208
• Category: Article
• ISSN: 0008-6215
• DOI: 10.1016/0008-6215(90)80109-g

✦ Synopsis

N-Acetylmuramoyl-L-alanyl-D-isoglutamine (MDP), a fragment of bacterial peptidoglycan, is capable of replacing whole mycobacteria in complete Freund's adjuvant'. In the course of our investigation of the relationship between the chemical structure and biological activities of MDP, it has been revealed that chemical modifications of the carbohydrate moiety produce various, important effects on the manifestation of the biological activities. MDP analogs in which the hydroxyl group at C-l of the sugar skeleton is replaced by hydrogen' or an acylthio group4 show the same potent immunoadjuvant activity as MDP. On the other hand, the replacement of the oxygen in the pyranose ring by a sulfur atom' reduces the activity, indicating the importance of closely retaining the conformation of the sugar skeleton. Very recently Barton et ~1.~ reported the synthesis of carbocyclic analogs of MDP, but their biological activities were not described.

It is well known that 1,5-dideoxy-1,5-imino-b-glucitol (1-deoxynojirimycin), which is a glucose analog with an NH group substituting for the ring oxygen, has a potent inhibitory effect on a-glucosidase owing to a structural resemblance to glucose'.

In view of these facts, we now describe as part of our continuing research on structureactivity relationships in the MDP series the synthesis and immunoadjuvant activity of N-acetyl-1 ,Sdideoxy-1,5-imino-muramoyl-L-alanyl-D-isoglutamine. RESULTS AND DISCUSSION We employed 2-azido-4,6-0-benzylidene-N-(tert-butoxycarbonyl)-1,2,5-trideoxy-1 ,5-imino-b-glucito18 (l), derived from 1,5-dideoxy-1,5-imino-D-glucitol (l -deoxy-* Studies on immunoadjuvant active compounds, Part 42. For Part 41, see ref. 1.