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Glycocoating of Oligovalent Amines Synthesis of Thiourea-Bridged Cluster Glycosides from Glycosyl Isothiocyanates.

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[6] Single ci-ystals of 2a were obtained from n-pentane at - 78 'C. C,,H,,N,Nb,
M , = 400.41. yellow block (0.51 x 0.43 x 0.38 mm). triclinic. space group Pi
(no. 7). 0=885.9(1), h=1065.5(1), r.=1276.7(1)pm. 2=70.47(1). p =
X549(1).;. =70.58(1) V=10704(2)x10' p m 3 . 2 = 2.pCaiib=1.242gcm-',
I.;,,,,, = 424:p = 5.7cin~'.lPDS(STOE&CIE),Mo,,.i
=71.073 pm.oscillation. 3 nun per image, 11965 intensities were collected at T = - 100 C. After
LP and combined decomposition and absorption correction 3446 (R,,, =
0 027316:)) were considered as independent reflections. The structure was
solved by ii combination of direct methods and difference-Fourier syntheses
(STRUX-V. SIR-92, SHELXS-93. full matrix). All heavy atoms were refined
with anisotropic. all H atoms with isotropic displacement parameters.
convergence a t KI = Z(11,'il - lFcll)/ZIFo~
= 0.0255. wR2 = [ZIV(F:- F':)';
Zw(Ff)']I = 0 0680 [ii = az(F:) + (0 0417 P), 0.57 P mit P =
+ 2 Ff) 31. GOF = 1.070 for 3446 reflections [/> 0.00(/)]and 348 variables.
A linal difference-Fourier synthesis remained without remarkable features
= + 0 30, - 0.38 e k ' ) [9](71 3 a . ' H N M R (400MHz. C,D,.
25 C. TMS): 6=1.29 (d. 1 2 H ;
'J(H.H) = 6.7 Hz; CH(CH,),), 3 22 (s, 12H: N(CH,),). 4.11 (sept. 2 H ;
3.1(H,H) = 7 0 H7: CH(CH,),). 5.92 (s. 5 H ; C,H,), 6.97 (t. 1 H:
'J(H.H) =7.3 Hz. p - C J f , ) , 7.11 (d. 2 H ; 'J(H.H) =7.3 Hz, M-C,H,);
"Ci'Hi NMR (100.4 MHz. C,D,, 25 'C. TMS): 6 = 24.7 (CH(CH,),). 27.4
(Cff(CH3)2).
52 1 (N(CH,d,), 108.2(C,H5). 122.9(i7i-C6H3).123 1 (p-C6HJ),
143 0 (n-C,H <). 152.8 (ipso-C,H,).
181. 4 % ' H NMR (400 MHz. C,D,. 25-C. TMS): 6 =1.31 (d. 12H: 'J(H.H) =
.
7.0 Hz. CH(C/f,),), 1 55 (s. 3 H ; C(CH,),), 1.58 (s, 3 H ; C(CH,),). 2.88 ( s .
6 H : N ( C H , ) ? ) , 4.04 (sept. 2 H : 'J(H.H) = 7 0 Hz; CH(CH,),). 5.48 (s, 2 H ;
C5HL).5.53 (s. 2 H , C,H,). 6.18 (s. 4 H : C,H,), 6.96 (t. 1 H: 'J(H.H) =
7.5 H r . p - C , / / , ) . 7.09 (d. 2 H ; 'J(H.H) =7.5 Hz, n - C , H , ) ; "C{'H) NMR
(100.4 MH;.. C,D,. 25 C. TMS) 6 = 24 4 (CH(CH,),). 25.2 (C(CH,),). 28.1
(('H(CHt)2).28.4 (C(CH,),). 36.3 (C(CH,),), 54.2 (N(CH,),). 90.9. 106.7.
112.5, 114.0 (CqH4),122.9 (tii-C<,HJ, 123.8 (p-C6H,), 142.8 (ipso-CSH,).
143.7 (o-C6H3).152.6 (ipt~-C,H,~).
4b: ' H N M R (400 MHz. C'D,. 70-C,
TMS). 6 = I 32 (d, 12H: 'J(H.H) =7.3Hz: CH(CH,),). 1.49 (s. 3 H :
C(C//,)z).15X (s, 3 H . C(CH,),). 2.93 ( s . 6 H ; N(CH,),). 3.99 (sept. 2 H ,
"J(H. HI = 7 0 Hz: CH(CH,),), 5-01 (s, 2H. C,H,), 5.51 (m, 2 H : C,H,). 6.08
(m,2H:CsH,).6.2X(m.2H:C,H,).6.9l
(t. 1 H ; 'J(H,H) ~ 7 . Hz.p-C,HJ.
6
7.15(d.ZH. ' J ( H . H ) = ~ . ~ H Z . I ? ~ - C , H , ) . ' ~ C NMR(100.4MHz.C6D,.
:'H~
70 c', TMS). 0 = 24.4 (CH(CH,),). 25.5 (C(CH,),). 28.1 (CH(CH,),). 29.4
(C(CH,),). 364(C(CH,),). 53.3 (N(CH,),), 89.4. 108 3 . 113.2. 116.1 (C,H,).
122.4 (iii-C,,H<).123.1 (p-C,H,). 143.7 (o-C,H,). 145.3 (Ipso-C,H,). 152.2
(ipso-CsH .,)
[9]Single crystals o f 4 a were obtained from n-heptane at -30 C. C,,H,,N,Nb.
M , = 482.51. orange plate (0.39 x 0.38 x 0.31 mm). monoclinic, space group
P 2 , I I (no. 14). (i =1000.3(1), h = 2186 l(1). c =1153.I(l) pm. [<= 95.29(1)'.
V = 2510.8(4) x 10' pm'. 2 = 4, pc4,cd
= 1.276 gcm-'.
Fooo =1016. p =
4 9 c m . ' . IPDS (STOE&CIE), Mo,,. i=71.073 pm. oscillation. 2.5 min per
image. 18328 intensities were collected at T = - S O T . After LP correction
4322 (R,,,,= 0.021 5 ( F i ) ) were considered independent reflections. The slructure was solved by a combination of direct methods and difference-Fourier
syntheses (STRUX-V. SIR-92, SHELXS-93, full matrix). All heavy atoms were
refined with anisotropic. all H atoms with isotropic displacement parameters;
convergence at R1 = Z(/l~'-;l - l & l l ) ; Z l ~ [= 0.0295 ivR2 = [ Z I V ( F-~ F:)'/
L w ( ~ ~ ) ' ] '= 0.0649 [ii.-' = o'(FJZ) (0 0476 P), +0.14 P, mit P = (F:
2
F:) 31. <;OF= 1.072 for all 4322 reflections [/>0.00(/)] and 419 variables. A
final difference-Fourier synthesis remained without remarkable features
*/ = + 0.30 - 0.38 e k ' ) . Further details of thecrystal structure investigations may be obtained from the Fachinformationszentrum Karlsruhe, D76344 Eggenstcin-Leopoldshafen(Germany), on quoting the depository numbers C'SD-405082 (2a) and CSD-405083 (4a).
[lo] 5 a : ' H N M R ( 4 0 0 M H z . C , D 6 . 2 5 C.TMS):6=1.00(s.3H;C(CH3),). 1.32
(5. 3 H : C ( C H , ) , ) . 1.33 (d. 12H: 'J(H.H) =7.0Hz: CH(CH,),). 3.89 (sept.
2 H . 'J(H.H) =7.0H7: CH(CH,),). 5.51 (pseudo q. 2H: J ( H . H ) = 2 H z :
C J / , ) . 5.85 (pseudo q. 2 H . J ( H , H ) = 2 Hz; C,H,). 6.03 (pseudo q. 2 H ;
J(H. H ) = 3 H I . C 5 H 4 ) ,6.30 (pseudo q. 2 H : J(H.H) = 3 Hz; C,H,), 6 85 (t.
1 H . ' J ( H . H ) = 7 . 5 H z . p ~ C n H I ) .7.06(d. 2 H ; ' J ( H . H ) = 7 S H z . n7-C6H,);
"CC('H: NMR (100.4 MHz. C,D6. 25 C. TMS): d = 22.1 (C(CH,),). 24.1
(C(CH,),). 24.4 (CH(CH,),), 27.7 (CH(CH,),). 36.4 (C(CH,),). 95.4. 105.7.
1154. 118.3 (C,Hd), 122.6 (m-C,H,). 123.1 (p-C6H,), 139.8 (rpsu-C,H,).
140.9 ( o - C J I ~ ) .154.5 (il,.~o-C,H,). 5b: triclinic space group Pi (no. 2).
n=951.4(1). h =1071.9(1). c=1138.5(l)pm. ~ = 7 6 . 4 4 ( 1 ) , 8=83.16(1),
;. = 80 3 h ( l ) Deiailed description of the synthesis and structure: W. A. Herrmnnn. W. Bnratta. €. Herdtweck. 0l;punorni~tallics1996, in press.
[I 11 a ) A. D Jenkis. M. F. Lappei-t. R. C. Srivastava. J Organomet. Clien?.1970,23,
165: b) J S. Bd%. D. C. Bradley. M. H. Chisholm. J C h ~ n iSot.
.
A 1971. 1433.
.
+
(cf
.
'
An,q,ii.. Chri?~.
/lit
+
Ed. Enxl. 1996. 35. No. f 7
+
t> VCH
Glycocoating of Oligovalent Amines : Synthesis
of Thiourea-Bridged Cluster Glycosides from
Glycosyl Isothiocyanates**
Thisbe K. Lindhorst* and Christoffer Kieburg
Many cell adhesion phenomena are based on the specific interactions of carbohydrates and proteins."] Important examples
include the transfer of leucocytes to areas of acute or chronic
inflammation, which is initiated by the interaction of selectins
with the sialyl Lewis" tetrasaccharide,['' and the phagocytosis of
bacteria, which is prompted by carbohydrate- protein interact i o n ~ . ' Microbial
~]
adhesion is in many cases also dependent on
the recognition of carbohydrates on the surface of the host cells
by specific l e ~ t i n s . ' ~The
] so-called mannose-binding protein
(MBP),r51an acute phase protein of immune response, recognizes a broad array of oligosaccharide moieties on the surface of
bacteria, which it is able to distinguish from its own sugar epitopes.161There is even evidence that carohydrate - lectin interactions are a key requirement for processes leading to neuronal
o~tgrowth.~''
Suitable glycomimetics that are able to compete with or even
perform better than the naturally occurring carbohydrate
ligands are needed for the elucidation and manipulation of carbohydrate-protein interactions.['l For this purpose the clustering of glycosides has proved to be advantageous in many instances, as the multipresentation of specific sugar epitopes in
one molecule can result in remarkably increased avidities in the
adhesion systems examined."] This phenomenon has been
termed the cluster effect and was first shown for the galectin on
hepatocytes.['*l Since then the clustering of glycosides has been
examined in particular for the inhibition of the influenza virus
hemagglutinin." '1 Copolymerization reactions'' 2 1 or telomerizations'' 31 have often been used to incorporate several
oligosaccharides; meanwhile an increasing number of dendrimers has appeared as core molecules for the synthesis of
clustered glycosides with exactly defined structures.r141Recently
the clustering of the sialyl Lewis" tetrasaccharide has been also
investigated for the control of leucocyte trafficking."
We have lately described a facile method for the preparation
of glycosyl isothiocyanates, which gives access to these versatile
carbohydrate derivatives on a multigramm scale." 61 We now
demonstrate that glycosyl isothiocyantes are ideally suited for
the preparation of cluster glycosides. The ease of the transformation of isothiocyanates and amines to thiourea derivatives
can generally be applied to the reaction of glycosyl isothiocyanates with oligovalent, multibranched amines to yield
oligoantennary, thiourea-bridged glycoconjugates directly.
We have tested the reaction with the trivalent tris(2aminoethy1)amine (I) and mono- as well as disaccharide glycosyl isothiocyanates of different configurations and obtained the
triantennary products in very good yields. The sugar units can
be deprotected easily in a ZCmplen reaction with sodium
methanolate in methanol without attack on the thiourea bridges
(Scheme 1). Thus the acetylated gluco-, manno-. galacto-, cellobio-, and lacto-configurated glycosyl isothiocyanates were
[*] Dr. T. K. Lindhorst, C. Kieburg
Institut fur Organische Chemie der Universitit
Martin-Luther-King-Platz 6, D-20146 Hamburg (Germany)
Fax: Int. code +(40) 4123-4325
e-mail. tklind(r, chemie.uni-hamburg de
I**] This work was funded by the Deutsche Forschungsgemeinschdft and the Fonds
der Chemischen Industrie. We wish to thank Prof. J. Thiem for his valuable
support We thank Dr. V. Havlicek for the electrospray-MS experiments.
Dipl. Chem. A. Jacob for the MALDI-TOF-spectrum, and Dr. V. Sinnwell for
the high temperature NMR measurements.
VerlugsgesellschufrftmbH. 0-6945f Weiniieirn, 1996
0570-0833:96/35f7-f953
$
f5.00+ .25 0
1953
COMMUNICATIONS
RO
R4
Ac
cs
1. CH2C12, reflux
2. NaOMeIMeOH. 20%
==?
Glycosyl isothiocyanate
Config.
R1
R2
PlaCfO
H
OAc H
R3
t%WCO
H
OAc H
a-manno OAC H
H
Pgalacto H
OAc OAc
pceliobio H
OAc H
=k:
Cluster Yield
Glycoside
["I./
R4
OAc
2
80
OAC
3
85
H
4
71
p(l,4)Glc(OAc)q 5
68
P(1,4)Gal(OAc)4 6
76
Scheme 1. Reaction of tris(2-aminoethylfamine ( 1 ) with glycosyl isothiocyanates to
cluster glycosides 2-6.
converted in two steps into the tris(2-glycosylthiourea-ethyl)amines 2-6 in overall yields of 70-85%.["]
The anomeric sugar configuration is determined by the glycosyl isothiocyanate used and does not change during the reaction.
However, the base-catalyzed 0 + N migration of the acyl
groups from the acetyl-protected glycosyl isothiocyanates onto
the amino termini of the core molecules was troublesome. If the
reaction was not carried out carefully enough, only the divalent
bis(glycosy1thiourea) cluster was formed, while the third amino
group was acetylated and therefore blocked. This unwanted side
reaction resulted in lower yields and structural defects in the
periphery of the cluster. It was suppressed by an appropriate
reaction procedure: a diluted solution of the oligovalent core
molecule was added dropwise to a solution of the glycosyl isothiocyanate in dichloromethane at reflux temperature.
This method can also be applied to the synthesis of higher
branched clusters, in which dendritic polyamines serve as
7
1954
0 VCH
OR
suitable core molecules. These
core molecules are easily
obtained by the exhaustive
Michael addition of methyl
acrylate to initial amines and
the subsequent amidation of
\\
the resulting esters with an exS
cess of ethylenediamine to af\
ford amidoamines. The reiteration of this two step reacR = H.
hexose
tion sequence results in the
doubling of peripheral animo
funtionalities; thus higher
branched structures are assembled in each developing
generation.
This construction
HO
principle leads to the so-called
RO
PAMAM (polyamidoamine)
JGeld triantennary thiourea-bridged
dendrimers as in the work
of Tomalia et al.[lsl In this
way the hexavalent amine 8
was synthesized from tris(2aminoethy1)amine (1) as well as the tetravalent amine 7 and
the next octaantennary generation 9 starting from ethylenediamine.
For the synthesis of bigger clusters we focused on the application of rnannosyi isothiocyanate for the coupling reaction, as we
were especially interested in clustered mannosides for the investigation of mannose-sensitive adhesion systems.['91 As expected
2,3,4,6-tetra-0-acety~-x-~-mannosyl
isothiocyanate reacted easily with the tetrafunctional amine 7 to give the tetraantennary
cluster 10, with the hexafunctional core 8 to yield the hexaantennary conjugate 11, and with the octavalent dendrimer 9 to afford the octaantennary cluster mannoside 12 in very good yields
of 76,69,and 55 70,respectively. The reaction can be carried out
following the same basic protocol for a variety of clusters.
Bigger clusters have to be dissolved in D M F instead of
dichloromethane, and the reaction times lengthened. The purification of all presented products was successfully performed on
Ho
.OH
a
Verlagsgeselischuft mhH. 0-69451 Weinheim, 1996
o57cl-clX3319613517-1954$15.00i.25jO
Angew. Chem. I n [ . Ed. Engi. 1996, 35. No. f 7
COMMUNICATIONS
Table 1. Selected ' H and "C NMR shifts of the glycoclusters
10-12 in D,O.
f
O Y N H
' H NMR (400 MHz):
glycosyl H-l
CH, groups
of the core region
A
-:yn
10
11
12
6
6
6
5.37 (4H)
5.37 ( 6 H )
5.37 (8H)
3.62 (8H)
3.32 ( 8 H )
286(8H)
2.72 (4H)
2.43 ( 8 H )
3.66 (6H)
3.30 ( 6 H )
2.75(9H)
2.62 ( 3 H )
2.23 ( 6 H )
3.65 (16H)
3.31 (24H)
2.99(12H)
2.90 (16H)
2.73 (SH)
2.51 (8H)
2.41 (16H)
182.62
174.75
82.70
182.67
175.28
82.78
182.60
175.01
82.12
50.1 1
49.28
44.41
39.32
32.33
51.35
49.70
4945
44.47
3934
33 03
51.89
49.91
49.60
49.19
44.43
39.26
37.04
32.69
31.97
"C NMR (69.89 MHz):
a.
S
c=s
c=o
glycosyl c-l
CH, groups
of the core region
&
no
n
n
12
OH
silica gel. The acetylated compounds yielded glasses; the watersoluble, deprotected cluster glycosides were obtained as white
powders after lyophylization.
All products were examined by means of 'H and 13C N M R
the integrals for these signals and for the signals of the
methylene protons of the core are correct for each product
as formulated. The N M R spectra of the acetylated clusters
were recorded in DMSO, where the required number of NH
spectroscopy and mass spectrometry. The NMR spectra show
resonances for every compound were observed between 6 =7.2
a single signal pattern for all sugar units; the ratios of
and 9.5.
Angeii. (%mi. Inr G I . G i g / . 1996, 35.
No. 17
VCH Verlogsgesellschu/~ mhH, 0.69451 Weinhrim. 1996
o570-o~33j9~~3517-1955
B 15.00+ .-75/0
1955
COMMUNICATIONS
The dynamic behavior of the aliphatic core chains resulted in
signal broadening in the ' H N M R spectra of the synthesized
cluster glycosides, especially for the thioamide protons, the
methylene peaks of the core region, and the anomeric protons of
the sugar antennae. For the same reason some signals in the 3C
spectrum, for example the signals related to the methylene
groups were hardly or not at all detected when the spectrum was
recorded at room temperature. These effects were less intense
for the deprotected compounds and when D,O was used as the
solvent. High-temperature measurements led to an improved
resolution of the multiplets in the 'H N M R and to the detection
of the complete signal pattern in the carbon spectrum (Table 1).
In the case of the octaantennary compound 12, the methylene
carbon atoms of the central ethylenediamine moiety can only be
seen with a highly concentrated sample.
MALDI-TOF mass spectrometry was a well-suited method
for the mass analysis of the largest cluster 12 ( M , =
3199.69 gmol-l). The protonated molecu~arion peak was the
only signal in the MALDI-TOF M S spectrum of 12.
We have shown here that glycosyl isothiocyanates can be
linked with dendritic ~Dolyamines to give
- thiourea-bridged cluster glycosides with defined structures. The method requires
simple starting materials, two reaction steps only, and easily
permits the variation of the carbohydrate epitopes, as well as the
number of branches, by choice of different core molecules. It
facilitates the rapid preparation of cluster glycosides of different
kinds on a multigramm scale.
[12] a) A. Spaltenstein, G. M. Whitesides. J. Am. Chem. Soc. 1991, 113, 686-687;
b) K. H. Mortell. M. Gingras, L. L. Kiessling, ibid. 1994, 116. 12053-12054.
1131 a) S. Aravind, W. K. C. Park, S. Brochu, R. Roy, Terrahedron Lett. 1994. 35,
7739-7742: b) W. K. C. Park. S. Aravind. A. Romanowska. J. Renaud, R. Roy,
Metliod.7 Enz.vmol. 1994,242,294-304; c) R. Roy, D . Zanini, S. J. Mennier, A.
Romanowska, ACS Symp. Ser. 1994. 560. 104- 119.
1141 a) R. Roy. D. Zanini. S. J. Meunier, A. Romanowska, J Chem. SO<.Chem.
Comtnun. 1993, 1869-1872, h) T. Toyokuni, A. K. Singhal. Chern. SOC.Rer.
1995. 231-242: c) R. Roy, W K. C. Park. Q. Wu, S.-N. Wang, Tetrahedron
Lett. 1995.36.4377--4380;d ) D Zdnini, W. K. C. Park, R. Roy, ;bid. 1995,36,
7383-7386, e) K. Aoi, K. Itoh. M. Okada. Macromolecules 1995.28, 53915393: f) N. Jayaraman, S. A. Nepogodiev. J. F. Stoddart, Ahstr. Pap. Eurocarh
V I I l (Seville) 1995. A-148: g) R. Roy in Modern Meth0d.Y in Carbohydrate
S>.nthr.sis(Eds: S. H. Khan. R. A. O'Neill), Harwood, Amsterdam. 1996, pp.
378 -402.
[15] a) G. Kretzschmar. U. Sprengdrd, H . Kunz, E. Bartnik, W. Schmidt, A.
Toepfer, B. Horsch, M. Krause, D . Seiffge. Terrahedron 1995, 51, 1301513030; b) U. Sprengdrd, M. Schudok, W. Schmidt. G. Kretzschmar. H. Kunz,
Angeir.. Chem. 1996. 108. 359-362: Angen. Chem. Int. Ed. Engl. 1996. 35,
321 -324.
[16] T. K. Lindhorst. C. Kieburg. Synthesi.s 1995. 1228--1230.
[17] Tris[2-(2
6-tetra-O-acetyl-a-~-mannopyranosyl)thiourea-ethyl~amine(C,,H,,N,O,?S,): FAB-MS: mi;: 1314 ( M + H + ) , 1336 ( M + N a + ) ; [a]iO=
+50.4 (c =1.0 in CH,CI,), ' H N M R (400MHz. DMSO): 6 = 8.75 (d. 3H.
NHCH). 7.61 (hr. s. 3H. NHCH,), 5.95 (dd. 3 H , H-1). 5.39 (dd, 3H. H-3).
5.1 1 (m. 6 H, H-2. H-4), 4.18 (dd. 3 H, H-6). 4.00 (dd. 3H, H-6). 3.89 (ddd, 3H,
H-5). 3.60 (d. 6 H , CH,NH), 2.72 (t. 6H. CH,N), 2.13, 2.02, 2.01, 1.97 (je s,
je 9H. l2OAc) J(NH.Hl) = 8.0, 5(2,3) = 3.5. J(3,4) = 9.7, 44.5) = 9.6,
J(5.6) = 5.1, J(5,6) = 2.5.46.6') = 12.2 Hz; I3C N M R (62.89 MHz, DMSO):
6 =182.84 (C=S), 170.03, 169.64. 169.61, 169.39 (C=O),79.20 fC-1). 69.28.
68 98. 68 43. 66 09 (C-2. C-3. C-4. C-5). 62 01 (C 6). 52 08 (CH,N), 41 99
(CH,NH), 20.62, 20.57, 20.45. 20.43 (COCH,). Tris[2-(a-D-mannopyranosyl)thioureaethyl]amine 3 (C2,H5,N,0,$J: Electrospray MS: mi;: 810
( M + H + ) : [Y]:* = +91.5 (c=1.0 in H,O): ' H N M R (400MHz, D,O):
6 = 5.55 (br. s, 3H. H-I), 4.08 (br. s, 3H. H-2). 3.89-3.86 (rn, 6 H , H-3, H-6).
3.78 (dd, 3H. H-6). 3.74-3.69 (m, 9 H , H-4. CH,NH). 3.57 (ddd. 3H. H-5).
2.87 ( t , 6H, CH,N); 43.4) = 9.1, 44.5) = 9.1. 5(5,6) = 2.1, 4 5 . 6 ) = 6.4,
I3C N M R (62.89 MHz. D,O): 6 =181.94 (C=S), 82.84
4 6 . 6 ) ~ 1 2 . Hz;
2
(C-1). 74.02, 70.94, 69 95, 67.72 (C-2, C-3, C-4, C-5). 61.27 (C-6), 52.78
(CH,N). 43 11 (CH,NH); J(H1,Cl) =165 H r .
[18] D. A. Tomalia. A. M. Naylor. W. A. Goddard 111, Angm.. Chem. 1990, 102,
119-157: Angeii.. Chrm. Inr. Ed. Engl. 1990, 29, 113-151.
[19] In collaboration with the research center in Borstel we are currently testing the
dependence of the inhibitory properties of cluster mannosides in the agglutination of type 1 fimbriae from Escherichia coli and yeast cells on the structure and
number of antennae of the examined compounds (cf. N. Firon, S. Ashkenazi,
D. Mirelman, I. Ofek, N. Sharon, Infect. Immun. 1987.55.472-476). In addition, cluster mannosides are needed for the investigation of the biological
functions of glycoproteins from the CD66 gene cluster (cf. S. L. Sauter, S. M.
Rutherford, C. Wagener, J. E. Shively. S. A. Hefta. J. B i d . Chem. 1993. 268.
15510-15516).
'
L
Exnerimental Procedure
12: A solution of generation 1 PAMAM dendrimer 9 (40 mg. 0.028 mmol) in D M F
(10 mL) was added dropwise to 2,3,4.6.-tetra-0-acetyl-a~mannopyranosylisothiocyanate (122 mg, 0.31 mmol, 11.2 equiv) in dichloromethane(50 mL) at reflux temperature. It was stirred a t reflux for 6 b. then the solvent was removed by distillation,
and the residual syrup was purified by flash column chromatography (silica gel
0.04-0.063 mm; CH,CI,/MeOH, 9/l). The acetylated reaction product was dissolved in dry inethanol (80 mL). and the solution was adjusted to p H 8-9 with a
freshly prepared 1 N sodium methanolate solution. The reaction mixture was stirred
at 40°C until the reaction was complete, then it was neutralized with ion exchange
resin (Dowex. H + W50x8), and the ion exchanger was filtered offand washed with
water. The resulting solution was distilled to remove the methanol and lyophilization. The octaantennary cluster mannoside 12 was obtained as a white lyophilizate
(49 mg, 0.015 mmol).
Received: March 21, 1996 [Z8961 IE]
German version: Angeis. Chem. 1996. 108,2083-2086
Keywords: dendrimers
*
glycoconjugates
glycosyl thioureas
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1956
f:)
VCH Verlagge.sellsc/i~ftmbH, 0.69451 Weinhrim. 1996
Synthesis of a Water-Soluble Conjugated
[3]Rotaxane**
Sally Anderson* and Harry L. Anderson*
~
Organic molecules with extended conjugated n-systems have
many
potential applications, for example as dyes for nonlinear
.
Optics and in electroluminescent displays.['] However, the small
HOMO-LUMO energy gaps that are responsible for the specia1 electronic properties of these compounds also make them
reactive, SO chemical instability often limits the usefulness of
[*I Dr. S. Anderson, Dr. H. L. Anderson
University of Oxford, Dyson Perrins Laboratory
South Parks Road, GB-Oxford OX1 3QY (UK)
Fax: Int. code +(1865)275-674
e-mail: harry.anderson(a~dyson.ox.ac.uk
[**I This work was supported by an Award to Newly Appointed Science Lecturers
from the Nuffield Foundation and by a gift of trimethylsilyacetylene from
Farchan Laboratories (Florida, USA). S. A. gratefully acknowledges a research fellowship and generous support from Trinity College, Cambridge
0570-0833/96/3517-/9S6 S /S.(JO+ .25/O
Angeir. Chem. Inr. Ed. Engl. 1996. 35.
NO.
17
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synthesis, clusters, bridge, glycosides, glycosyl, glycocoating, thioureas, oligovalent, amines, isothiocyanate
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