ω-AMINOALKYL β-GLYCOSIDES OF N-ACETYLMURAMYL-L-ALANYL-D-ISOGLUTAMINE, AND THEIR CONJUGATES WITH MENINGOCOCCAL GROUP C POLYSACCHARIDE

Article abstract of DOI:10.1016/0008-6215(83)88218-4

The 6-aminohexyl β-glycoside of N-acetylmuramyl-L-alanyl-D-isoglutamine and its spacer-arm-linked analog (3.8 nm) were synthesized from 2-methyl-(3,4,6-tri-O-acetyl-1,2-dideoxy-α-D-glucopyrano)-<2,1-d>-2-oxazoline, and coupled with meningococcal group C polysaccharide in attempts to enhance the immunogenicity of the polysaccharide antigen.

Full text of DOI:10.1016/0008-6215(83)88218-4

58
M.M. PONPIPOM, K. M. RUPPRECHT
RESULTS AND DISCUSSION
2-Methyl-(3,4, 6-tri-O-acetyl- 1,2-dideoxy-~-D-glucopyrano)- [2,1 -d]-2-oxazoline,
prepared by the method of halide-ion participation in the presence of base s, was
treated with 6-(benzyloxycarbonylamino)-l-hexanol as reported in the literature9.
The product, compound 1, was deacetylated with sodium methoxide in methanol to
b
o
R o . ~ ~ N .~
~
O
~
,
N
HZ
AcHN
AcHN
1 R
- -
Ac
3
R
-
-
H
2 R
=
H
4 R -" CH3CHCO2H
Z
--'- PhCH20CO
H2COH
~
a
,
.
.
0
0
AcHN
NHZ
--a,..
iA ~ c H NO ~ N H R
/ C / / / H
/ C i//H
Me
~Ib
•
CO-L-AIo-D-isoGI n (OBzl)
CO-L-Ala- O-isoGIn
6
R
- -
H
0
give 6-(benzyloxyearbonylamino)-l-hexyl 2-acetamido-2-deoxy-p-D-glueopyrano-
side9,1o (2). Acetalation of 2, followed by alkylation with L-2-ehloropropanoie acid11
afforded 4 in good yield. The blocked glycopeptide 5 was prepared from 4 and L-
alanyl-D-isoglutamine benzyl ester hydrochloride12 by the mixed-anhydride method.
Hydrogenolysis of 5 gave crystalline (6-aminohexyl)/~-glyeoside (6) of N-aeetylmura-
myl-L-alanyl-D-isoglutamine, which could be used as an intermediate for spacer-arm
extension.
The 3.8-nm spacer-arm 9 was prepared from ethyl N-[N-acetyl-S-(carboxy-
methyl)-DL-homocysteinyl]glycinateI (8) and 1-amino-6-(tert-butoxycarbonylamino)-
hexane13. Condensation of the carboxyl analog (10) of 9 with 6, followed by acid
treatment, gave the amine 12. The two amine-containing ligands 6 and 12 were
then coupled with meningococcal group C polysaccharide via the N-hydroxysueeini-