i s
4722
The isolation from biological materials of a com- found that a supersaturated solution of D-glUC0pound composed of amino sugar and higher fatty samine is obtained when a suspension of D-glucoacid has not been reported, but this group of amino samine in an adequate volume of methanol is
sugar derivatives is of great interest because amino treated with an equivalent amount of sodium methsugars are sometimes found in combination with oxide. The supersaturated, methanolic solution
fatty acids, e.g., in the lipopolysaccharides of some of D-glUCOSamine so formed can be maintained for
microorganisms. The present work was under- some time a t room temperature in concentrations as
taken for the purpose of investigating the prepara- high as 10% or more, and upon the addition of a
tion and properties of some X a c y l and -V-acyl- slight excess of an acid anhydride a t room temtetra-0-acyl derivatives of D-glucosamine (2-amino- perature an almost quantitative yield of quite pure
2-deoxy-~-glucose),
in which the acyl group was de- ,V-acyl-D-glucosamine is precipitated. N-Benzoylrived from even-numbered saturated fatty acids.
D-glucosamine which was previously preparedlo by
Some acyl derivatives of this amino sugar with the action of benzoyl chloride was also prepared by
lower fatty acids have been previously reported in this method from benzoic anhydride.
This procedure offers a simplified method for the
the literature. Wholly and partially acetylated
D-glucosamines have been extensively investi- preparation of ;Vi-acetyl-D-glucosamine.l1 This imand de- portant derivative of D-glucosamine has hitherto
gated, and ~V-propionyl-~-glucosamine~
rivatives of iY-formyl-, N-propionyl- and N- been prepared from D-glucosamine hydrochloride
butyroyl-D-glucosamine5 have been prepared. in methanol by the action of acetic' anhydride and
There is only one report, by Jones, Kaye and Sta- silver acetate'?; or with acetic anhydride and ancey,6 concerning the preparation of a higher fatty hydrous sodium acetatel'j ; in IV,AV-dimethylformacid derivative of D-glucosamine, namely, S- amide with acetic anhydride a t low temperature,
stearoyl-tetra-O-stearoyl-D-glucosamine. Some and in aqueous methanol with acetic anhydride in
fatty acid derivatives of D-glucose have been syn- the presence of Dowex-1.l 4 The present method
needs no catalyst and no particular treatment, but
thesized.?
The N-acylation and polyacylation of D-glUC0- gives preparations of high purity in good yield.
samine were carried out with fatty acid anhydrides The crude N-acetyl-D-glucosamine that inimediand chlorides.. Treatment of D-glucosamine with ately starts to crystallize from the methanolic
the acid anhydrides in anhydrous methanol or with supersaturated solution of D-glucosamine on the adthe acid chlorides in water (with alternate addition dition of acetic anhydride with completion oi
of sodium hydroxide) gave rise to the N-acylated crystallization overnight in the refrigerator has
D-glucosamines, and treatment of D-glucosamine m p . 200 to 204O, being sufficiently pure for ordiwith acid anhydrides in pyridine or with acid nary purposes. One recrystallization raised the
chlorides in a mixture of chloroform and pyridine melting point to 208" (uncorrected).
produced the iT-acyl-tetra-0-acyl-D-glucosamines. The action of fatty acid chlorides on D-glucoThe N-acylation was most effectively carried out saniine resulted in smaller yields and lower purity
by the addition of the respective acid anhydrides of the obtained Ali-acylated-D-glucosamines than
to a supersaturated, methanolic solution of D-gluco- did the action of the acid anhydrides on D-glucosamine. It is known that D-glucosamine is lib- samine, and the chlorides of lower fatty acids gave
crated from its salts by treatment with strong variable yields of the corresponding X-acyl-Dbasesss9and that i t is slightly soluble in alcohol (1 glucosamines. Concerning the higher homologs,
part in 38 of boiling methanol8). However, it was the preparations from the acid chlorides showed
physical constants identical with those from the
(1) \V. I H a v m r t h . P \V K e n t a n d hI Stacey, J C h e m S o c . , 1220
(1948); X f . I k a w a . J. B. Koeyfli, S G. h f u d d a n d C. Niemann. THIS corresponding acid anhydrides.
J O L ~ R N A I , 75,
,
3439 (19.53): cf 0 \Vestghal a n d 0 Liideritz, iliigeru
~~-A~cy~-tetra-O-acy~-D-g~ucosamines
were prer'hein , 66, 407 (1954).
pared
by
either
one
or
both
methods
in
which the
f ? ) .4. R . Foster and h i S t a c e y ,
acid anhydride or acid chloride was allowed to re247 ( I W )
(:%I P. \V. Kent and .\I \\-. IVhitehousr, "Biochemistry of thi, act with D-glucosamine, D-glucosamine hydro.4minosugars," Butterworths. I,ondon, 1933.
chloride or ~!'-ac~-l-D-glucosamine. Preparations
(4) R . Kuhn and I:. Haber. Cheni. H e i . , 86, 7 2 2 ( 1 Y . X )
t.5) .4. Neuberger a n d R . 1'. Pitt Rivers, Biochem. J . , 33, 1380
(l!l:w).
l
S t a c e y , J . C h c w Sot., X I ( j
(6) A . S. Jonrs, I T . A . (;. K;IW i l n ~ \I.
(10) hl. Bergmann and I,. Zervas, ibid., 64, 975 (1931); 65, 1201
(1932).
T
SOME F A T T Y
4'728
ACIDDERIVATIVES
O F D-GLUCUSAhlINE
TABLE
I
ACID DERIVATIVES
OF D-GLUCOSAMINE
FATTY
M.p.,O C,
Methods
Derivatives
AV-Acyl
N-Acetyl'
N-Butyroyl
S-Caproyl
A'-Capryloyl
S-Caprinoyl
N-Lauroyl
N-Myristoyl
N-Palmitoyl
.V-Stearoyl
A, B
A
4,c
A, C
A, C
A, C
A, C
A, C
Pentaacyl
Pentaacetyl'
Pentabutyroyl
Pentacaproyl
Pentacapryloyl
Pentacaprinoyl
Pentalauroyl
Pentamyristoyl
Pentapalmitoyl
PentastearoylQ
E:, H
D, H
D, G. I
G, I
G, I
G
F
F, I
F
.Mixed acyl
N-Acetyl-tetra-0-caprinoyl
Tetra-0-acetyl- Ar-caprinoyl
N- Acetyl-tetra-0-lauroyl
N-Acetyl-tetra-0-palmitoyl
A-Caprinoyl-tetra-0-palmitoyl
Tetra-0-caprinoyl-S-stearoyl
I
H
I
I
I
I
c
c
w
W
W
C
S
S
S
W
W
W
W
[a]oC
Yie1ds.d
(with solvent)
%
208
212
217-218
215
212-213
208-209
198
202-203
194-195
..
S
S
W
W
W
23
40
GO
74
66
..
43.10
47.97
52 15
55 17
57 02
59.43
61 50
63.56
G5 10
0.84
7.68
8 36
8 91
9.37
9 76
10.09
10.38
10.63
!L82
7.46
8.21
8.83
9.32
9.73
10.11
10.3G
10.80
49.36
5.95
5 Yti
CsiHvOioN
CuH380inS
84-86
80-84
63-64
53-54
88
92
90
6.33
6.62
5.0:
4,59
4.20
3.88
3 GO
3.35
3.14
3 ti0
2.04
2 09
1 73
70.78 6 9 . 9 2 l O . ! l 2 1 0 . 0 0 1 . 1 7
72 68 72 82 I 1 37 11 53 1 . 2 8
74.18 74 20 11 71 11 6 8 1 . 1 4
7 5 . 3 6 75.55 11.99 11 95 1 . 0 %
76.30 7 6 . 2 9 12.21 12.27 0 . 9 3
49.35
71
63
97-100
97-98
82-83
78
75-76
Carbon, 'A
Hydrogen,');
Sitrugen, '%
Calcd. Found Calcd. Found Calcd. Found
43.43
18.18
51.97
55.06
57.83
59.81
61.G7
63.28
64.68
4.
4.
4.
4.
4.
4.
q.
q.
4.
138-139
Formula
CssHioaOlaN
C7?HiaaOioPI'
CioH~siOioK
CuHiip0:oN
70 76
73 60
74.78
72.36
70.05
74.07
74 74
72.33
10 92
11.58
11.84
11.29
9 91
11.58
11.81
12.45
6.21
5.27
4.71
4.40
3.92
3.83
3.51
3 06
2 90
3.iil
21!i
2 38
L(i3
l.!i3
1.17
1.2d
1.05
0.9:
1 e7
2 79
1 47
1.47
2.39
1.3ii
1.09
1.0Y
..
1.32 1.28
a A, action of acid anhydride on D-glucosamine in MeOH; B, acetic butyric anhydride on D-glucosamine in MeOH; C,
acid chloride and NaOH on D-glucosamine in water; D, acid anhydride on D-glucosamine in pyridine; E, acid anhydride on
D-glucosamine hydrochloride in pyridine; F, acid chloride on D-glucosamine hydrochloride in pyridine and chloroform; G,
acid chloride on D-glucosamine in pyridine and chloroform; H, acid anhydride on N-acyl-D-glucosamine in pyridine; I,
acid chloride on N-acyl-D-glucosamine in pyridine and chloroform.
C, crystalline; S, sirup ; W , waxy-crystalline.
Unless specified for mutarotation, the values are for those after standing for 24 hr. ; solvent: W,water; P, pyridine; C, chloroq. stands for almost quantitative and the yields of fully acylated derivatives are those after one or two recrystallizaform.
tions. * Roseman and Ludowieg14 report m.p. 210" (corrected?, [ a ] " D +41.0. f Westphal and HolzmannO report for
iv-acetyl-tetra-0-acetyl-cu-D-glucosamine
m.p. 139", [ a ]*OD +92 .
Jones, Kaye and StaceyB report m.p. 71-72", [a]
2 5
+16".
Water
+"
Methanol
*
+
Hot
ethanol
Crystalline
tb
Sirup
Waxy-crystalline
a N-Acetyl-tetra-0-acetyl-D-glucosamine,particularly the
p-isomer, is slightly soluble.
N-Acetyl-D-glucosamine is
sparingly soluble.
T h e solubility decreases with the increase in rnrhon atom? of t h r aryl group for N-aryl derivatives.
+
+"
3724
U.I~VOUYE,
K. ONODERA,
S. KITAOKA
AND
s. H I R A N O
Vol. $8