[Synthesis and biological activity of anomeric muramoyldipeptide butylglycosides].
The synthesis of anomeric butyl glycosides of muramyl dipeptide was reported. alpha-Butyl glycoside of N-acetyl-D-glucosamine was 4,6-O-benzylidenated and the benzylidene derivative was 3-O-alkylated by the Williamson reaction with sodium (S)-2-chloropropionate. The resulting protected alpha-butyl glycoside of muramic acid was then condensed with L-Ala-D-iGln-OBzl by the DCC-HOSu method. Mild acidic hydrolysis and subsequent catalytic hydrogenolysis of the resulting glycopeptide yielded the target alpha-butyl glycoside of N-acetyl-L-alanyl-D-isoglutamine. In the synthesis of beta-butyl glycoside of N-acetylmuramyl-L-alanyl-D-isoglutamine, 2-acetamido- 4,6-di-O-acetyl-2-deoxy-3-O-[(R)-1-(methoxycarbonyl)ethyl]-alpha- D-glucopyranose, a 1-OH derivative of muramic acid, was the key compound. Its interaction with the excess thionyl chloride resulted in the corresponding glycosyl halide, which was condensed with n-butanol according to Helferich. O-Deacetylation, 4,6-isopropylidenation, and subsequent alkaline hydrolysis of the resulting compound gave the protected beta-butyl glycoside of muramic acid. Its activation and condensation with L-Ala-D-iGln-OBzl and the subsequent removal of protective groups were performed in the same manner as the reactions in the synthesis of alpha-butyl glycoside of N-acetyl-L-alanyl-D-isoglutamine. The adjuvant activity of the butyl glycosides to HIV proteins rgp160 and rgp120 and their ability to affect in vitro HIV replication and the proliferation of mouse spleen T-cells were examined. The biological activity of anomeric muramyl dipeptides was shown to depend essentially on the configuration of their anomeric center.
Pertel'
S S
SS
Frunze State University, Simferopol, Ukraine. orgchem@ccssu.crimea.ua
Kadun
A L
AL
Kakaian
E S
ES
Chirva
V Ia
VIa
Krivorutchenko
Iu L
IuL
Krivoshein
Iu S
IuS
Bakova
A A
AA
Andronovskaia
I B
IB
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000737:chemistry*; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D006027:Glycosides; D000119:Acetylmuramyl-Alanyl-Isoglutamine