Toward fully synthetic homogeneous glycoproteins: A high mannose core containing glycopeptide carrying full h-type2 human blood group specificity

Article abstract of DOI:10.1002/1521-3773(20010504)40:9<1728::AID-ANIE17280>3.0.CO;2-1

Blood typing with the ABO classification is based on cell-surfacse glycoproteins. In a significant step toward the synthesis of these compounds, the laboratory synthesis of a fully functional N-linked glycopeptide featuring H-type blood group determinants 1 is described.

Full text of DOI:10.1002/1521-3773(20010504)40:9<1728::AID-ANIE17280>3.0.CO;2-1

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[1] a) M. J. Zaworotko, Angew. Chem. 2000, 112, 3180 ± 3182; Angew.
Chem. Int. Ed. 2000, 39, 3052 ± 3054; b) D. M. L. Goodgame, D. A.
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1995, 378, 703 ± 706; c) V. A. Russell, C. C. Evans, W. Li, M. D. Ward,
Science 1997, 276, 575 ± 579.
Toward Fully Synthetic Homogeneous
Glycoproteins: A High Mannose Core
Containing Glycopeptide Carrying Full
H-Type2 Human Blood Group Specificity**
Zhi-Guang Wang, Xufang Zhang, Michael Visser,
David Live, Andrzej Zatorski, Ulrich Iserloh,
Kenneth O. Lloyd, and Samuel J. Danishefsky*
[3] a) J. M. Lehn, Supramolecular Chemistry: Concepts and Perspectives,
VCH, Weinheim, 1995, pp. 139 ± 198; b) C. J. Jones, Chem. Soc. Rev.
1998, 27, 289 ± 299; c) D. Phip, J. F. Stoddart, Angew. Chem. 1996, 108,
1242 ± 1286; Angew. Chem. Int. Ed. Engl. 1996, 35, 1154 ± 1196.
[4] a) M. J. Zaworotko, Angew. Chem. 1998, 110, 1269 ± 1271; Angew.
Chem. Int. Ed. 1998, 37, 1211 ± 1213; b) L. Carlucci, G. Giani, M.
Moret, D. M. Proserpio, S. Rizzato, Angew. Chem. 2000, 112, 1566 ±
1570; Angew. Chem. Int. Ed. 2000, 39, 1506 ± 1510; c) S. R. Batten, R.
Robson, Angew. Chem. 1998, 110, 1588 ± 1595; Angew. Chem. Int. Ed.
1998, 37, 1461 ± 1494.
Carbohydrate domains in the context of glycolipids and
glycoproteins carry significant messages. The definition of the
full scope and impact of oligosaccharide-based bioinformatics,
falls within the scope of the rapidly growing field of
glycobiology.[1] The sorting out of the diverse effects of
glycosylation on phenomena ranging from protein folding[2] to
cascades with a bearing on fertilization,[3] inflammation,[4] and
metastasis,[5] constitutes a major challenge to glycobiology.[6]
Other phenomena that are communicated in the ªgrammarº
of carbohydrate structure include aberrant glycosylation
patterns, associated with tumorigenesis, and blood typing.[7]
The most widely known of the carbohydrate-centered serol-
ogy systems, the ABO classification, is based on structural
patterns of cell-surface glycoproteins on erythrocytes.[8]
From the perspective of chemistry, one of the issues
complicating molecular level understanding of the conse-
quences of glycoarchitecture is the phenomenon of hetero-
geneity. While the various carbohydrate domains present on a
glycoprotein may be isolated and purified, this tends to be
feasible only after detachment of the oligosaccharide ensem-
ble from its macromolecular setting. One method for dealing
with the issue of the inhomogeneity of glycoproteins is
through synthesisÐeither chemical, enzymatic, or a combi-
nation of both.[9]
[5] S. Leininger, B. Olenyuk, P. J. Stang, Chem. Rev. 2000, 100, 853 ± 908,
and references therein.
[6] a) M. Fujita, Chem. Soc. Rev. 1998, 27, 417 ± 425; b) N. Takeda, K.
Umemoto, K. Yamaguchi, M. Fujita, Nature 1999, 398, 794 ± 796.
[7] a) B. F. Abrahams, S. J. Egan, R. Robson, J. Am. Chem. Soc. 1999, 121,
3535 ± 3536; b) M. Scherer, D. L. Caulder, D. W. Johnson, K. N.
Raymond, Angew. Chem. 1999, 111, 1690 ± 1694; Angew. Chem. Int.
Ed. 1999, 38, 1587 ± 1592; c) R.-D. Schnebeck, E. Freisinger, B.
Lippert, Angew. Chem. 1999, 111, 235 ± 238; Angew. Chem. Int. Ed.
1999, 38, 168 ± 170.
[8] S. B. Copp, S. Subramanian, M. J. Zaworotko, J. Chem. Soc. Chem.
Commun. 1993, 1078 ± 1079.
[9] H. Li, A. Laine, M. OꢁKeefe, O. M. Yaghi, Science 1999, 283, 1145 ±
1147.
[10] S. S.-Y. Chui, S. M.-F. Lo, J. P. H. Charmant, A. G. Orpen, I. D.
Williams, Science 1999, 283, 1148 ± 1150.
[11] a) C.-Y. Su, B.-S. Kang, Q.-G. Wang, T. C. W. Mak, J. Chem. Soc.
Dalton Trans. 2000, 1831 ± 1833; b) C.-Y. Su, B.-S. Kang, Q.-C. Yang,
T. C. W. Mak, J. Chem. Soc. Dalton Trans. 2000, 1857 ± 1862; c) C.-Y.
Su, B.-S. Kang, H.-Q. Liu, Q.-G. Wang, T. C. W. Mak, Chem. Commun.
1998, 1551 ± 1552.
[12] ªPLATON program:º A. L. Spek, Acta Crystallogr. Sect. A 1990, 46,
194 ± 201.
[13] IR (KBr): nÄ ˆ 3396, 3067, 1626, 1543, 1497, 1476, 1452, 1385, 1278,
1115, 1086, 747, 627 cm 1; elemental analysis (%) found: C 42.37, H
5.11, N 13.12.
A long-term goal of our laboratory has been the develop-
ment of methodology and strategies which would enable the
synthesis of complex oligosaccharides bearing the inherent
information in a context that simulates the natural glycopro-
tein setting. As will be shown below, advances in the field are
[14] IR (KBr): nÄ ˆ 3432, 3067, 1697, 1626, 1543, 1498, 1476, 1452, 1386,
1278, 1114, 1088, 748, 628 cm 1; elemental analysis (%) found: C
46.12, H 4.85, N 13.22, possibly corresponding to [Cu6(Acntb)6]-
(ClO4)6 ´ 22H2O ´ 6(CH3COCH3), calcd: C 46.34, H 4.74, N 13.04.
[15] M. Moon, I. Kim, M. S. Lah, Inorg. Chem. 2000, 39, 2710 ± 2711.
[16] K. D. Benkstei, J. T. Hupp, C. L. Stern, Angew. Chem. 2000, 111, 235 ±
238; Angew. Chem. Int. Ed. 2000, 39, 2891 ± 2893.
[*] Prof. S. J. Danishefsky,[‡] Dr. Z.-G. Wang, X. Zhang, Dr. M. Visser,
Dr. A. Zatorski, Dr. U. Iserloh
The Laboratory for Bioorganic Chemistry
Sloan ± Kettering Institute for Cancer Research
1275 York Avenue, Box 106, New York, NY 10021 (USA)
Fax : (‡1)212-772-8691
Dr. D. Live
The Department of Biochemistry, Molecular Biology, and Biophysics
University of Minnesota, Minneapolis, MN 55455 (USA)
Dr. K. O. Lloyd
The Laboratory for Tumor Antigen Immunochemistry
Sloan ± Kettering Institute for Cancer Research
1275 York Avenue, New York, NY 10021 (USA)
‡
[ ] The Department of Chemistry
Columbia University, Havemeyer Hall, New York, NY 10027 (USA)
[**] This work was supported by the National Institutes of Health (Grant
nos.: HL-25848 and CA-28824 (to S.J.D.), and CA-710506 (to
K.O.L.)). Postdoctoral fellowship support is gratefully acknowledged
by Z.-G.W. (US Army breast cancer grant no.: DAMD17-97-1-7119)
and M.V. (NIH grant no.: CA-62948-04). We gratefully acknowledge
Dr. George Sukenick of the Sloan ± Kettering Instituteꢁs NMR core
facility for mass spectral and NMR spectroscopic analyses (SKI core
grant no.: CA-08748).
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such that a construction is now
possible. Our specific focus in
this project was a maximally
convergent, stereospecific syn-
thesis of a homogeneous N-
acetyllactosamine glycopeptide
bearing an N-linked bidomainal
high-mannose core, connected
through lactosamine spacers to
sectors carrying the carbohy-
drate-encoded information.[10]
For this demonstration, we fo-
cused on the total synthesis of a
glycopeptide construct that
presents human H-type2 specif-
icity in a naturally occurring,
glycan-like setting. Herein, we
describe a solution to this prob-
lem in the context of the syn-
thesis of 1 (see Scheme 5).
OTBS
BnO
BnO
BnO
OTBS
O
BnO
BnO
BnO
O
OTBS
OTBS
O
BnO
BnO
BnO
BnO
O
BnO
BnO
O
O
O
a
glycal assembly
O
PMBO
O
PMBO
O
SEt
O
OBz
3
4
BnO
HO
BnO
BnO
O
O
O
BnO
b
PhSO2HN
2
OTBS
BnO
BnO
BnO
OH
O
BnO
BnO
BnO
*
O
c
OTBS
BnO
BnO
BnO
OH
O
O
BnO
BnO
BnO
*
O
inversion
BnO
O
OAc
O
O
BnO
PMBO
BnO
O
BnO
BnO
O
PMBO
O
O
O
O
O
O
O
BnO
*
O
OBz
BnO
BnO
PhSO2HN
PhSO2HN
6
5
Scheme 1. Synthesis of core pentasaccharide 6. a) 1. DMDO/CH2Cl2; 2. EtSH/TFA/CH2Cl2, 75% (two steps);
3. BzCl/Py/DMAP, 90%; b) MeOTf/CH2Cl2/DTBP,75%; c) 1. LiAlH4/THF/ 208C !08C; 2. Dess ± Martin
periodinane/CH2Cl2/228C; 3. l-selectride/THF/228C; 4. Ac2O/Py/DMAP/CH2Cl2, 82% (four steps); 5. TBAF/
THF, 77%. Bn ˆ benzyl, Bz ˆ benzoyl, DMAP ˆ 4-dimethylaminopyridine, DMDO ˆ dimethyl dioxirane,
DTBP ˆ 2,6-di-tert-butylpyridine, PMB ˆ para-methoxybenzyl, Py ˆ pyridine, TBAF ˆ tetrabutylammonium
fluoride, TBS ˆ tert-butyldimethylsilyl, Tf ˆ triflate ˆ trifluoromethanesulfonyl, TFA ˆ trifluoroacetic acid.
Glycal assembly logic had
been used for the large-scale
syntheses
of
2
and
3
(Scheme 1).[11, 12] Unfortunately,
coupling of 2 with the glycal
epoxide directly available from
3 occurs, at best, in poor yield.
A body of chemistry to deal
with just such a contingency
had been developed (see
3 !4 !5).[13] System 5 had been
organized such that a C-2 hy-
droxyl group in the C ring (see
asterisk in 5) could be exposed
from a unique benzoate. Epi-
merization of the resultant al-
cohol (by oxidation/reduc-
tion),[14] followed by acetylation
at C-2 and deprotection of the
unique ring D and ring E silyl
ethers, gave rise to 6 with de-
fined acceptor sites at the two
ªwingº mannose units (see as-
terisks in 6).
AcO
AcO
OAc
O
BnO
AllO
OBn
O
BnO
AllO
OBn
O
OAc
O
OBn
O
OBn
O
b
a
O
O
BnO
O
SEt
AcO
BnO
AcO
BnO
BnO
NH
SO2
7
8
9
TMS
BnO
AllO
BnO
OBn
O
OBn
O
donor
OBn
O
OBn
O
*
d
c
ClCH2COO
O
BnO
O
SEt
SEt
BnO
BnO
BnO
PhthN
PhthN
10
11
acceptor
*
Scheme 2. Synthesis of lactosamine building block 11. a) 1. NH3/MeOH; 2. Bu2SnO/C6H6; 3. allyl bromide/
Bu4NBr; 4. BnBr/NaH/DMF, 50% (four steps); b) 1. IDCP/TMSCH2CH2SO2NH2, 83%; 2. EtSH/LiHMDS/
DMF, 85%; c) 1. CsF/DMF, 908C, 94%; 2. phthalic anhydride/Py/228C; 3. Piv2O, then Ac2O, 100% (two steps);
d) 1. Ph3RuCl/DABCO/THF; 1n HCl, 74%; 2. (ClCH2CO)2O, DMAP/DTBP, 97%. All ˆ allyl, DABCO ˆ 1,4-
diazabicyclo[2.2.2]octane, DMF ˆ dimethylformamide, HMDS ˆ 1,1,1,3,3,3-hexamethyldisilazane, IDCP ˆ
iodonium dicollidine perchlorate, PhtH ˆ phthaloyl, Piv ˆ pivaloyl, TMS ˆ trimethylsilyl.
We next concerned ourselves
with fashioning the lactosamine spacer region, which charac-
teristically intervenes between the bifurcated high mannose
core sector and the bioinformation domains. For the purposes
of this work, we focused on interpolation of an acetyllactos-
amine element on each wing of the mannose sector. Herein,
we use the two-directional mannose building block 11 (see
Scheme 2) as a single insertion unit in the two branching
domains. However, the chemistry described here could be
extended to the building of longer spacer sectors by controlled
homocoupling of 11.
horizon, trans diaxial addition of iodonium 2-(trimethylsilyl-
ethanesulfonamide) (SES) to the glycal double bond was fol-
lowed by thiolysis, which triggered migration of the sulfon-
amide from C-1 !C-2 with concurrent ejection of iodide from
C-2 to form 9.[16] Deprotection of the nitrogen and phthaloy-
lation[17] (to form 10), followed by deallylation and reprotec-
tion at C-3, afforded 11, which was equipped with activatable
donor and acceptor sites (marked by asterisks in Scheme 2).
A concise fashioning of the H-type antigen is shown in
Scheme 3. The galactal donor system 12 was actuated by strict
a-face epoxidation. The a-epoxide coupled to 13, notwith-
standing the hindered nature of its acceptor site (marked with
an asterisk). The C-2' alcohol specifically unveiled in the
coupling step serves as the acceptor site for the l-fucosyl
Our synthesis of 11 commenced with peracetylated lactal 7.
This was converted into 8, which bears a unique allyl
protecting group at C-3' (Scheme 2).[15] Following chemistry
that we had developed with this type of application on the
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Much planning and trial and
error research went into accom-
plishing the global deprotection
of the 15-mer (Scheme 5). The
four phthaloyl groups of 21, as
well as the hindered acetate on
the C ring, were deprotected
concurrently. We next carried
O
OBn
O
OTIPS
O
O
O
OBn
O
OTIPS
O
O
BnO
OBn
O
OBn
O
*
HO
O
BnO
O
O
BnO
O
SEt
BnO
BnO
a
b
O
O
NHSO2
12 + "OH"
13
O
O
OBn
OBn
F
OBn
OBn
BnO
BnO
TMS
O
15
16
OBn
OBn
BnO
14
out the iodosulfonamidation of
the glycal linkage at the reduc-
ing end of the 15-mer. This
addition was followed by hydro-
lytic rearrangement (a four-step
sequence). The critical massive
BnO
OBn
O
OBn
O
BnO
OBn
OBn
O
BnO
BnO
O
c
O
O
SEt
d
SEt
NHPhth
BnO
BnO
O
O
NH2
O
O
OBn
OBn
OBn
18
17
OBn
BnO
BnO
deprotection step could now be
realized. Thus, 37 benzyl groups
and the sulfonamido function
were all reductively cleaved
Scheme 3. Synthesis of ªwingº trisaccharide 18: a) 1. DMDO/CH2Cl2; 2. ZnCl2; 3. SnCl2/AgOTf/DTBP/CH2Cl2,
50% (three steps); b) 1. TBAF/THF; 2. BnBr/NaH/DMF, 81% (two steps); 3. IDCP/TMSCH2CH2SO2NH2;
4. EtSLi/DMF/ 408C ± 08C, 75% (two steps); c) CsF/DMF/1008C, 5 days, 65%; d) 1. phthalic anhydride/Py/
228C; 2. Ac2O, 97% (two steps). TIPS ˆ triisopropylsilyl.
through the agency of sodium/
ammonia.[19] Remarkably, the terminal hemiacetal linkage
was sufficiently robust such that there was no detectable
reduction to an alditol under these conditions. Furthermore,
selective acetylation of the lone amino function in the A ring
was readily achieved in the polyhydroxyl substrate system.
This remarkable sequence led to the free hemiacetal 22, which
was, in turn, converted into 23 by ammonolysis of the masked
aldehyde.[20] In the concluding step, the polyhydroxyl glyco-
sylamine 23 coupled with differentiated pentapeptide 24 to
produce the desired b-glycosyl N-linked glycopeptide target
system 1 (m/z: calcd 3305 [M ]; found 3328 [M‡Na] ).[21]
While the yield of this compound may appear modest,
detailed NMR spectroscopic analysis fully corroborates that
compound 1 meets the standard of homogeneity while
displaying its H-type2 serological determinant in the context
of an N-acetyllactosamine gly-
donor 14. This glycosylation leads to the a-l-fucoside 15. The
glycal found in 15 was advanced to 18 (through 16 and 17)
with chemistry previously developed on simple systems with
such applications in mind.
We next turned to the assembly of these carefully crafted
subunits. The program commenced with twofold coupling of 6
with 11 (Scheme 4). Fortunately, this goal could be accom-
plished in good yield to produce the 9-mer 19 through an
apparently stereospecific sulfonamidoglycosylation reaction,
modulated by the neighboring phthalamido linkages.[18] The
two positionally defined acceptor sites (marked with aster-
isks) of the nonasaccharide were unveiled as shown. Fortu-
nately, coupling of 20 with H-type donor 18 occurs at each of
the lactosamine moieties, again under mediation by methyl
triflate, to afford 15-mer glycal 21.
‡
‡
copeptide. The availability of
such an advanced N-linked gly-
copeptide provides excellent
opportunities for probing glyco-
architecture and its biological
consequences. As seen in Fig-
ure 1, the 1H NMR spectrum
(800 MHz) of the 15-mer oligo-
saccharide system linked to the
5-mer peptide is extremely well
resolved and suggestive of
structural order. Detailed anal-
ysis of mutual conformational
effects between the oligosac-
charide and peptide domains
using high level NMR spectro-
scopic techniques will be re-
ported separately.
In addition to the critical
nuclear magnetic resonance
spectroscopic and mass spectro-
metric measurements that sup-
port our structural claim on
behalf of compound 1, it was
ˆ
Scheme 4. Synthesis of the protected 15-mer glycal 21. a) MeOTf/CH2Cl2/Et2O/DTBP, 62%; b) (NH4)2C S/
EtOH/NaHCO3, 99%; c) trisaccharide 18/MeOTf/CH2Cl2/Et2O/DTBP, 78%.
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HO
HO
HO
b
a
O
O
NH2
NHAc
O
15-mer glycal 21
O
OH
O
14-mer
14-mer
HO
NHAc
22
23
CO2H
OH
NH2
O
H
N
H
N
c
AcHN
N
N
H
H
H
O
O
O
24
NAc-Lactosamine
O
H-type 2
OH
HO
HO
OH
O
O
O
HO
HO
OH
O
5-mer Peptide
H2N
AcHN
HO
O
O
O
O
OH
O
HO
HO
OH
AcHN
HO
HO
HO
HO
O
H
NH
OH
O
O
HO
OH
O
OH
HO
O
Man
HO
HO
O
HO
O
HO
O
O
O
O
O
O
HO
AcHN
HO
AcHN
HO
HN
HN
O
OH
H-type 2
O
O
HO
O
OH
OH
O
O
HO
HO
OH
NAc-Lactosamine
OH
NH
HO
O
O
HO
O
O
O
NH
HO
AcHN
AcHN
Man
Man
Chitobiose
O
NHAc
1
Scheme 5. Synthesis of the fully synthetic and homogeneous 15-mer glycopeptide 1. a) 1. NH2CH2CH2NH2/EtOH; 2. Ac2O/Py/DMAP, 85% (two steps);
3. IDCP/NH2SO2Ph, 74%; 4. LiHMDS/AgOTf/THF/H2O, 63%; 5. Na/NH3/THF; 6. Ac2O/MeOH, 46% (two steps); b) NH4HCO3/H2O, 90%; c) peptide 24/
HOBt/HBTU/DIPEA/DMSO, 20%.[21] DIPEA ˆ diisopropylethylamine, DMSO ˆ dimethyl sulfoxide, HBTU ˆ O-(benzotriazol-1-yl)-N,N,N',N'-tetra-
methyluronium hexafluorophosphate, HOBt ˆ 1-hydroxy-1H-benzotriazole, Man ˆ mannose.
of interest to establish that the H-type constructs, so
presented, maintain functionality. Indeed, the presence of
operational H-type2 blood group determinants in the synthe-
sized product was confirmed by demonstrating its reactivity
with an antibody against H-type2 determinants (mAbSA) in
an enzyme-linked immunosorbant assay (ELISA; Figure 2).
This antibody is highly specific for H-type2 blood group
determinants and does not react with H-type1, Lea, or Lex
structures.[22, 23]
This synthesis serves to illustrate the current reach of the
glycal assembly method. More broadly it shows the extra-
Figure 1. A) 1H NMR (800 MHz) spectrum of 1 in D2O at 20 8C and pH 3.7
~
&
(phosphate buffer). B) Section of the spectrum of 1 in H2O at 5 8C and
pH 3.7 (phosphate buffer) showing the secondary NH signals of amides
from the peptide backbone, side chain, and GlcNAc sites. C) The anomeric
region of the 1H-13C HMQC spectrum at 800 MHz of 1 in D2O at 20 8C and
pH 3.7 (phosphate buffer).
Figure 2. Reactivity of glycopeptide 1 ( ), H-type2 active mucin ( ) as a
x
a
!
positive control, and Le /Le -active mucin ( ) as a negative control with
the antibody against H-type2 determinants (mAbSA) as determined with
an ELISA. The mucin preparations have been previously described (see
ref. [22]).
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COMMUNICATIONS
[18] a) T. Sasaki, K. Minamoto, H. Itoh, J. Org. Chem. 1978, 43, 2320;
b) Z. G. Wang, X. F. Zhang, Y. Ito, Y. Nakahara, T. Ogawa,
Carbohydr. Res. 1996, 295, 25.
[19] For a recent example featuring simultaneous removal of 17 benzyl
groups, see: W. Frick, A. Bauer, J. Bauer, S. Wied, G. Müller,
Biochemistry 1998, 37, 13421.
[20] a) L. M. Likhosherstov, O. S. Novikova, V. A. Derevitskaja, N. K.
Kochetkov, Carbohydr. Res. 1986, 146, C1; b) S. T. Cohen-Anisfeld,
P. T. Lansbury, Jr., J. Am. Chem. Soc. 1993, 115, 10531.
[21] HBTU/HOBt: a) R. Knorr, A. Trzeciak, W. Bannwarth, D. Gillessen,
Tetrahedron Lett. 1989, 30, 1927; b) A. Speicher, T. Klaus, T. Eicher, J.
Prakt. Chem. 1998, 340, 581.
ordinary progress in the field of oligosaccharide and glyco-
peptide synthesis. Given the extendibility of this chemistry to
virtually any type of saccharide presentation and the capacity,
in principle, for ligation of the pentapeptide construct to
larger polypeptide or protein domains,[24] the synthesis of
sequence-defined homogeneous glycopeptides, and thence
glycoproteins, is at hand. Studies directed toward reaching
fully functional glycoproteins by total synthesis are underway.
Received: January 22, 2001 [Z16470]
[22] Analysis of the fine specificities of 11 mouse monoclonal antibodies
reactive with H-type2 blood group determinants: K. Furukawa, S.
Welt, B. W. T. Yin, H.-J. Feickert, T. Takahashi, R. Ueda, K. O. Lloyd,
Mol. Immunol. 1990, 27, 723.
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Enhanced Physical Properties in a Pentacene
Polymorph
Theo Siegrist,* Christian Kloc, Jan H. Schön,
Bertram Batlogg, Robert C. Haddon, Steffen Berg, and
Gordon A. Thomas
Pentacene is a highly promising material for application in
thin film transistor devices because of its recently reported
high mobilities and good semiconducting behavior.[1] For this
reason, we have carried out a program to grow single crystals
of unusually high purity and crystalline perfection to study the
intrinsic properties of organic semiconductors. We have
produced millimeter-sized crystals with electrically active
impurities at concentrations of the order of 1013 cm 3 (or one
impurity molecule per 108 pentacene molecules) by using a
vapor-phase deposition technique. Such crystals were used for
[10] For a definition of glycoprotein classification and nomenclature, see:
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pp. 13 ± 28.
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Danishefsky, Angew. Chem. 2000, 112, 3798; Angew. Chem. Int. Ed.
2000, 39, 3652.
[*] Prof. Dr. T. Siegrist,[‡] Dr. C. Kloc, Dr. J. H. Schön,
Prof. Dr. B. Batlogg,[‡‡] S. Berg, Prof. Dr. G. A. Thomas
Bell Laboratories, Lucent Technologies
600 Mountain Avenue, Murray Hill, NJ 07974 (USA)
Fax : (‡1)908-582-2521
E-mail: tsi@bell-labs.com
Prof. Dr. R. C. Haddon
[14] With modification of the original procedure from: M. A. E. Shaban,
R. W. Jeanloz, Carbohydr. Res. 1976, 46, 138.
Departments of Chemistry and Physics
and Advanced Carbon Materials Center
University of Kentucky, Lexington, KY 40506-0055 (USA)
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F. E. McDonald, T. Oriyama, J. Am. Chem. Soc. 1992, 114, 8331.
[17] Piv2O (or Ac2O) is needed to dehydrate the initial adduct (amide) into
the phthalimide 10.
‡
[ ] Other address:
Inorganic Chemistry 2, Lund University (Sweden)
‡‡
[
] Other address:
Institute of Solid State Physics, ETH Zürich (Switzerland)
1732
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4009-1732 $ 17.50+.50/0
Angew. Chem. Int. Ed. 2001, 40, No. 9