Synthesis of cyclopropyl glycosides and their use as novel glycosyl donors

Article abstract of DOI:10.1016/j.carres.2012.03.008

Methods for the synthesis of cyclopropyl glycosides and their use as glycosyl donors are described. Cyclopropyl glycosides containing different substituents were prepared by cyclopropanation of the corresponding vinyl glycosides, or by glycosidation of cy

Full text of DOI:10.1016/j.carres.2012.03.008

Carbohydrate Research 356 (2012) 288–294
Contents lists available at SciVerse ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
Synthesis of cyclopropyl glycosides and their use as novel glycosyl donors
Clark Scholl a, Thomas Licisyn a, Christopher Cummings a, Kevin Hughes a, David Johnson b,
Walter Boyko a, Robert Giuliano a,
⇑
a Department of Chemistry, Villanova University, Villanova, PA 19085, United States
b GlaxoSmithKline Biologicals, 553 Old Corvallis Road, Hamilton, MT 59840, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Methods for the synthesis of cyclopropyl glycosides and their use as glycosyl donors are described. Cyclo-
propyl glycosides containing different substituents were prepared by cyclopropanation of the corre-
sponding vinyl glycosides, or by glycosidation of cyclopropyl alcohols that are synthesized by the
Kulinkovich reaction. 1-Methyl- and 1-phenyl-substituted cyclopropyl glycosides undergo coupling to
Fmoc-protected serine and threonine and to partially protected monosaccharides in the presence of
TMS triflate to give glycosidated products.
Received 31 January 2012
Received in revised form 7 March 2012
Accepted 8 March 2012
Available online 17 March 2012
Keywords:
Ó 2012 Elsevier Ltd. All rights reserved.
Cyclopropyl glycosides
Serine glycoside
Threonine glycoside
Cyclopropanols and alkoxycyclopropanes have been used as
homoenols and homoenolate equivalents in a variety of transfor-
mations in organic synthesis that are initiated by ring-opening.1,2
Recent applications include the conversion of oxygen-substituted
cyclopropanes to spirocyclobutanones by Prins-type reactions,3
in Scheme 1 may allow activation and coupling under mild activat-
ing conditions by treatment with a Lewis acid. Cyclopropyl glyco-
sides would be expected to be stable to a variety of conditions, and
should be accessible by cyclopropanation of vinyl glycosides, from
cyclopropyl alcohols, or from allyl glycosides once the double bond
is isomerized. In this paper we describe the synthesis of unsubsti-
tuted and substituted cyclopropyl glycosides, and their use as gly-
cosyl donors toward Fmoc-protected serine and threonine and
monosaccharides.
to oxepanes by Petasis–Ferrier rearrangement,4and to
a-methylke-
tones.5 Among cyclopropanated carbohydrates, those in which the
cyclopropane ring is fused at C2–C3 on the pyranose ring are the
most widely studied, and have been successfully used to synthe-
size 2-C alkyl branched-chain sugars, oxepines, heptoses, and other
products.2,6–9 We considered that cyclopropyl glycosides, which
are available from vinyl glycosides and by other means, may un-
dergo glycosidation under Lewis-acid activation (Scheme 1).
In their work on the structure of the plant toxin helminthosp-
oroside, Curini and Pellicciari demonstrated that a carboethoxy-
substituted cyclopropyl glycoside underwent fragmentation in
methanolic hydrogen chloride to produce methyl 4,4-dimethoxy-
butanoate (Scheme 2),10 presumably through loss of the
cyclopropyl group by an analogous process. Conceptually, the ring
opening-fragmentation pathway illustrated in Scheme 1 resembles
the cleavage of 1-methylcyclopropyl ethers (MCP ethers) and
(1-methyl)cyclopropyl carbamates, which have been used as
hydroxyl and amino protecting groups, respectively.11,12 MCPM
(1-methyl 10-cyclo propylmethyl) ethers have also been used as
hydroxyl protecting groups, and are cleaved under acidic
conditions.13
Cyclopropyl glycosides were prepared by three methods. The
first of these involves the conversion of tetra-O-benzyl-
D-glucopyr-
anose to mixed acetals by treatment with ethyl vinyl ether or
OR'
OR'
O
O
activation
"E+"
R'O
R'O
R'O
R'O
R'O
R'O
R
R
O
O
E
OR'
coupling
acceptor
O
R'O
R'O
OH
There have been no reports of the use of cyclopropyl glycosides
as glycosyl donors. We considered that the reactivity exemplified
R'O
O
acceptor
⇑
Corresponding author. Fax: +1 610 519 7167.
E-mail address: robert.giuliano@villanova.edu (R. Giuliano).
Scheme 1. Glycosidation via cyclopropyl glycosides.
0008-6215/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.carres.2012.03.008

C. Scholl et al. / Carbohydrate Research 356 (2012) 288–294
289
RO
OR
O
O
O
CH3OH
H+
O
H+
CH3O
CH3O
OEt
OEt
RO
H
RO
O
O
OEt
Scheme 2. Fragmentation of a cyclopropyl glycoside.
R'O
OBn
OBn
1.
O
O
BnO
BnO
BnO
BnO
PPTS
R
(R' = CH3; CH2CH3
R = H, CH3)
BnO
BnO
OH
R
O
1: R = H,
2: R = CH3
2. TMSOTf
CH2
iPr2NEt
(56-68%)
Cl3CCN
NaH
CH2I2
Et2Zn
(63-68%)
OBn
Ph
OBn
O
HO
3
O
BnO
BnO
BnO
BnO
.
BnO
BnO
BF3 OEt2
O
R
CCl3
O
(86%)
4
5a
: R = H (α)
NH
5b
: R = CH3 (α)
: R = Ph (β)
5c
Scheme 3. Synthesis of cyclopropyl glycosides.
2-methoxypropene. The mixed acetals are then cleaved by tri-
methylsilyl trifluoromethanesulfonate in the presence of an amine
base to give the vinyl glycosides 1 and 2 (Scheme 3). We previously
described this two-step sequence as a mercury-free method for the
preparation of vinyl glycosides and other vinyl-substituted carbo-
hydrates that were used as substrates in hetero-Diels–Alder
reactions.14,15
Cyclopropanation of the vinyl glycosides was carried out with
diethyl zinc and methylene diodide8 to give the corresponding
cyclopropyl glycosides 5a (R = H) and 5b (R = CH3). Initially, it
was difficult to isolate acceptable yields of the 1-methylcyclopro-
pyl glycoside 5b by this method, which involves quenching the
reaction with 1 M HCl. The replacement of the acid hydrolysis of
the reaction mixture with the addition of pyridine16 to precipitate
the zinc salts gave higher and more reproducible yields of 5b,
which could be prepared in gram quantities as a crystalline solid
that was stable indefinitely in the freezer (ꢀ10 °C). Compound 5b
is stable to amine and aqueous bases, and to Grignard reagents
at 0 °C.
Vinyl glycoside synthesis followed by cyclopropanation was a
convenient method to prepare unsubtituted and 1-methyl-substi-
tuted cyclopropyl glycosides 5a and 5b; however, the sequence
proved to be less practical for the preparation of the 1-phenyl-
substituted analog 5c. In this case, preparation of 1-phenylcyclo-
propanol by the Kulinkovich reaction,1,17 followed by Schmidt
glycosidation185c was successful. Synthesis of carboethoxy-substi-
tuted cyclopropyl glycoside 5d was performed by treatment of
vinyl glycoside 1 with rhodium acetate and ethyl diazoacetate
(Scheme 4).19,20 Cyclopropyl glycosides 5a and 5b were obtained
To study glycosidation using cyclopropyl glycosides, we initially
chose protected amino acid acceptors to avoid potential side reac-
tions that might result from the sensitivity of some carbohydrate
acceptors toward acidic reagents that may be required to activate
the cyclopropyl ring toward cleavage. Additionally, glycosidations
of serine and threonine are known to be problematic, thus success-
ful coupling reactions involving them would be synthetically use-
ful. In this study, coupling reactions of the cyclopropyl glycosides
were carried out using Fmoc-protected serine and threonine
methyl esters. Previously, low yields in the synthesis of serine
O-glycosides by the Koenigs–Knörr procedure have been ascribed
to poor nucleophilicity of the hydroxyl group that results from
intramolecular hydrogen bonding.21 Improved yields were ob-
tained by the use of imine derivatives of the amino acid acceptors
in glycosidations with glycosyl halides, as well as through the use
of other donors.22,23 We were interested in observing if cyclopropyl
glycosides could be used to glycosidate serine and threonine deriv-
atives for possible application to glycopeptide synthesis.24. Initial
results were not encouraging, as the unsubstituted cyclopropyl
glycoside (5a), as well as the carboethoxy-substituted compound
(5d) failed to undergo coupling with either Fmoc serine or threo-
nine in the presence of trimethylsilyl triflate (TMS triflate, TMSOTf)
or N-bromosuccinimide. Decomposition of the cyclopropyl glyco-
sides was observed but no products of coupling were isolated.
However, methyl- and phenyl-substituted cyclopropyl glycosides,
5b and 5c, underwent coupling with both Fmoc serine and threo-
nine methyl esters 6a and 6b in the presence of TMS triflate to give
glycosidated amino acids 7a and 7b (Scheme 5). Glycosidation of
Fmoc serine methyl ester with 5c proceeded in 90% yield. In all
as
a
anomers, 5c as the b anomer, and 5d as a mixture of
cases,
a glycosides were obtained as the major products over b.
diastereomers.
While stereoselectivities are modest, we are encouraged by the

290
C. Scholl et al. / Carbohydrate Research 356 (2012) 288–294
OBn
OBn
[Rh(OAc)2]2
O
O
BnO
BnO
BnO
BnO
N2CHCO2Et
(35%)
BnO
BnO
O
O
CO2Et
5d
1
Scheme 4. Synthesis of a carboethoxy-substituted cyclopropyl glycoside.
OBn
Fmoc
TMSOTf
CH2Cl2
NH
O
BnO
HO
BnO
CO2CH3
BnO
O
R
R'
5b
α
: R = CH3 ( )
6a: R' = H
5c: R = Ph (β)
6b: R' = CH3
OBn
O
7a
5b
: R' = H, 59% from , 2:1 α/β
BnO
BnO
5c
90% from , 2.4:1 α/β
Fmoc
HN
7b
5b
: R' = CH3, 58% from , 2:1 α/β
BnO
5c α/β
40% from , 1.4:1
O
CO2CH3
R'
Scheme 5. Coupling of cyclopropyl glycosides with Fmoc serine/threonine.
ease with which glycosidation occurs from these readily accessible
donors. The Fmoc protecting group, shown previously to be well
suited to the efficient glycosidation of Fmoc serine benzyl ester
with glycosyl bromides,25 also works well in glycosidations with
cyclopropyl glycosides.
anated carbohydrates derived from glycals,2,6 and products result-
ing from addition of the electrophile to a cyclopropyl carbon are
obtained in some examples. One question that is pertinent to our
study is whether or not it is TMSOTf or simply triflic acid that is
activating the cyclopropyl glycosides in the coupling reactions. In
the glycosidation of a cytovaricin subunit with a triethylsilyl glyco-
side using trityl perchlorate as the catalyst, it was shown that no
reaction took place in the presence of 2,6-di-tert-butylpyridine or
molecular sieves, which suggested that the true catalyst was per-
chloric acid.27. This was confirmed by successful glycosidations of
the same donor with Brønsted acids. Control experiments that
we conducted with 1-methylcyclopropyl donor 5a and Fmoc serine
methyl ester were less clear. While glycosidation did not occur in
the presence of an amine base, tetramethylurea, or molecular
sieves, coupling also did not take place when triflic acid was used
to activate the cyclopropyl sugar. Attempted glycosidations using
cyclopropyl sugars in the presence of other catalysts, including bis-
muth and aluminum triflates, were also unsuccessful. The develop-
ment of milder conditions would expand the utility of cyclopropyl
glycosides as donors, especially in oligosaccharide synthesis, as
illustrated in Scheme 6.
Trichloroacetimidate derivatives have been used successfully to
glycosidate Fmoc-protected serine esters with perbenzylated sug-
ars. The TCA derivative of a disaccharide was used to glycosidate
Fmoc-serine methyl ester in 86% yield, with ꢁ2:1
a
/b selectivity.23
Isopropenyl glycosides, used in our study for the preparation of
cyclopropyl glycosides, have been used as glycosyl donors in their
own right.26 For an additional comparison, we carried out the gly-
cosidation of 6a with isopropenyl glycoside 2, using TMSOTf as the
catalyst in dichloromethane. The ratio of a/b glycosides was again
2:1 and the isolated yield after chromatographic purification was
64%. We observed that the glycosidation of 6a with isopropenyl
glycoside 2 occurred more rapidly than with cyclopropyl glycoside
donor 5b or 5c. Glycosidations with isopropenyl glycosides are
known to proceed in either dichloromethane or acetonitrile, and
with higher b-selectivity in the latter. Due to solubility problems
of the reactants in acetonitrile, we were unable to attempt glycos-
idations in this solvent alone; however, the glycosidation of 5b
with 6a was successful in a mixture of 8:1 acetonitrile–dichloro-
methane. The reaction proceeded more slowly than it did in dichlo-
Glycosidation of methyl 2,3,4-tri-O-benzyl-a-D-glucopyrano-
side28,29
8 with 1-methylcyclopropyl glycoside 5b occurred
smoothly to give the 1,6-linked disaccharide 926,30 in 51% yield
after chromatography. However, the attempted glycosidation of
bis-Troc-protected acceptor 1031,32 gave a mixture of products
romethane, and the yield (48%) and stereoselectivity
(a/b
ratio = 4:1) were also different. Clearly there are differences in
reactivity between the cyclopropyl and isopropenyl glycosides.
While it is difficult to be definitive without additional examples,
our results do suggest that cyclopropyl glycosides are less reactive
toward activation with TMSOTf than isopropenyl glycosides, and
from which only
a-linked disaccharide 11 could be isolated in
28% yield based on recovered 5b. Glycosidation of 10 was of inter-
est to us because it has been used as a glycosyl acceptor in the syn-
thesis of lipid A analogs. Selective glycosidation of the C-6 hydroxyl
in the presence of the unprotected C-4 hydroxyl was achieved
through the use of glycosyl halides.31 That debenzylation occurred
and that the anomeric configurations at C1 in both carbohydrates
that the preference for
dependent.
a-glycoside formation is not as solvent-
The mechanism of glycosidation with cyclopropyl glycoside do-
nors likely follows the pathway suggested by Scheme 1. Reagents
such as mercury(II) trifluoroacetate, N-iodosuccinimide and
TMSOTf have been shown to initiate the ring-opening of cycloprop-
in the disaccharide are
a were established by extensive NMR
analysis using both 1D and 2D techniques. Debenzylation is likely
the result of the sensitivity of this acceptor to triflic acid that is

C. Scholl et al. / Carbohydrate Research 356 (2012) 288–294
291
OBn
OH
O
BnO
BnO
O
BnO
BnO
BnO
O
BnO
O
BnO
BnO
OCH3
8
OBn
BnO
O
OCH3
9
BnO
BnO
(51%, 3.8:1 α/β)
TMSOTf
CH2Cl2
BnO
OBn
O
CH3
HO
5b
O
BnO
BnO
BnO
HO
O
O
HO
OBn
O
O
HN
O
O
O
OCH2CCl3
HN
O
OH
OCH2CCl3
O
OCH2CCl3
10
OCH2CCl3
11
(28%)
Scheme 6. Disaccharide synthesis with cyclopropyl glycosides as donors.
produced in the glycosidation. Given that other products were not
characterized, it is not possible to ascertain the stereoselectivity of
the coupling of 5b and 10. However, the loss of the aglycone from
the acceptor and apparent absence of a b-linked disaccharide indi-
cate sensitivity of the glycosidic linkages at both anomeric posi-
tions. It is worth noting that a recent comparison of relative rates
of hydrolysis of methyl glucopyranoside derivatives that were
substituted at the C2 position revealed a greater rate for hydrolysis
of glucosides with C2 carbamate groups than that observed with
alkyl or alkanoyl groups.33
In this study, we have synthesized 1-substituted cyclopropyl
glycosides by cyclopropanation of isopropenyl glycosides and by
glycosidation of 1-substituted cyclopropanols. The use of pyridine
in the processing of the cyclopropanation of isopropenyl glycosides
rather than acid was critical, and allowed the crystalline 1-methyl-
cyclopropyl glycoside to be prepared efficiently. We have shown
that 1-methyl and 1-phenylsubstituted cyclopropyl glycosides
can be activated with TMSOTf and used as glycosyl donors in cou-
pling reactions. Both Fmoc-protected serine and threonine methyl
esters undergo glycosidation smoothly with these novel donors.
Carbohydrate acceptors were also used successfully, albeit in a lim-
ited number of trials. Additional experiments are needed to assess
the scope and synthetic utility of cyclopropyl glycosides in glycos-
idation with carbohydrates that possess more diverse substitution
patterns.
1.2. Cyclopropyl 2,3,4,6-tetra-O-benzyl-
a
-
D
-glucopyranoside 5a
To a stirring solution of vinyl 2,3,4,6-tetra-O-benzyl-a-D-gluco-
pyranoside 1 (0.73 g, 1.3 mmol) in anhydrous diethyl ether (2 mL)
was added diiodomethane (1.0 mL, 12.7 mmol) followed by diethyl
zinc (2.0 mL, 1 M in hexanes) under argon. The reaction mixture
was stirred for 19 h at rt then ether (5 mL) was added and the reac-
tion cooled to 0 °C. Pyridine (0.17 mL, 2.1 mmol) was added and the
solution became yellow in color. After stirring for an additional
hour at rt, the reaction was again cooled and a second portion of
pyridine (0.17 mL, 2.1 mmol) was added, turning the solution or-
ange. The reaction mixture was filtered through a Celite pad and
concentrated under reduced pressure to give crude product that
was purified by flash chromatography with 1:14:85 triethyl-
amine–EtOAc–hexanes as the eluent. Cyclopropyl glycoside 5a
was obtained as an oil; yield, 0.73 g (97%). A second chromatogra-
phy with 1:19:80 triethylamine–EtOAc–hexanes was used to
provide 0.51 g (68%) of analytically pure material for characteriza-
tion. Rf 0.48 (20% EtOAc–hexanes), ½a D
ꢂ
+122 (c 1.0, chloroform),
1H NMR d 7.34–7.11 (m, 20H, Ph-H), 4.96, 4.79 (ABq, 2H, J = 10.8,
PhCH2), 4.87 (d, 1H, J1,2 = 3.7, H-1), 4.75, 4.61 (ABq, 2H, J = 12.2,
PhCH2), 4.83, 4.47 (ABq, 2H, J = 10.8, PhCH2), 4.60, 4.47 (ABq, 2H,
J = 12.2, PhCH2), 3.94 (dd, 1H, J3,2 = 9.7, J3,4 = 9.1, H-3), 3.85 (ddd,
0
1H, J5,4 = 10.1, J5,6 = 3.8, J5,6 = 2.1, H-5), 3.72 (dd, 1H, J6,5 = 3.8,
J6,6 = 10.6, H-6), 3.65 (dd, 1H, J6 ,5 = 2.1, J6 ,6 = 10.6, H-60), 3.63 (dd,
1H, J4,3 = 9.1, J4,5 = 10.1, H-4), 3.55 (dd, 1H, J2,1 = 3.7, J2,3 = 9.7, H-
2), 3.42 (m, 1H, cyclopropyl), 0.844 (m, 1H, cyclopropyl), 0.637–
0.391 (m, 3H, cyclopropyl); 13C NMR d 2 ꢃ 138.8, 138.2, 138.1
(Ph-ipso’s), 128.3–127.4, 20C, overlapped (Ph-CH’s), 97.3 (C-1),
81.9 (C-3), 79.7 (C-2), 77.7 (C-4), 75.5, 74.9, 73.4, 73.0 (PhCH2’s),
70.4 (C-5), 68.5 (C-6), 51.0 (cyclopropyl), 5.71 (cyclopropyl), 4.63
(cyclopropyl).
0
0
0
1. Experimental
1.1. General procedures
Melting points were recorded on a Thomas-Hoover apparatus
and they are uncorrected. Thin-layer chromatography was carried
out on aluminum foil-backed silica gel plates (EMD) coated with a
fluorescent indicator. Plates were developed with cerium molyb-
date stain. Flash chromatography was carried out using 230–
400 mesh silica gel. NMR spectra were recorded on a Varian (Agi-
lent) Mercury 300 Plus spectrometer in CDCl3 for 1H NMR at
300.0 MHz, tetramethylsilane reference, d = 0.0 ppm, and, 13C
NMR 70.0 MHz, CDCl3 reference, d = 76.9 ppm. Spectral assign-
ments were confirmed using gCOSY, DEPT, 13C detected HETCOR,
and gHMBC experiments.
Anal. calcd for C37H40O6: C, 76.66; H, 6.78. Found: C, 76.55; H,
6.85.
1.3. 1-Methylcyclopropyl 2,3,4,6-tetra-O-benzyl-a-D-glucopyra-
noside 5b
To a stirring solution of isopropenyl 2,3,4,6-tetra-O-benzyl-a-D-
glucopyranoside 2 (0.37 g, 0.64 mmol) in anhydrous diethyl ether
(6 mL) was added diiodomethane (0.51 mL, 6.3 mmol) and diethyl

292
C. Scholl et al. / Carbohydrate Research 356 (2012) 288–294
zinc (0.97 mL, 1 M in hexanes, 5.7 mmol) dropwise with stirring
under argon. The reaction mixture was stirred for 14 h at rt then
cooled to 0 °C. Pyridine (0.08 mL) was added and the solution be-
came yellow in color. After stirring for an additional hour at rt,
the reaction was again cooled and a second portion of pyridine
(0.08 mL) was added, turning the solution orange. The reaction
mixture was filtered through Celite and using an additional portion
of ether (5 mL) and filtrate was concentrated under reduced pres-
sure to an oil that was purified by flash chromatography using
1:10:89 triethylamine–EtOAc–hexanes to give 0.34 g (89%) of
product as a colorless oil that solidified on storage at 0 °C. Recrys-
tallization from 80:20 hexanes–EtOAc gave white solid (0.24 g,
63%). In subsequent preparations it was found that the solid prod-
uct obtained after chromatography was suitable for coupling reac-
NMR d 138.4, 137.8, 137.7, 137.52 (Ph-ipso’s), 128.3–127.3 (19 res-
onances, overlapped C for both diastereomers, Ph-CH), 97.5 (C-1),
81.7 (C-3), 79.4 (C-2), 77.3 (C-4), 75.6 (PhCH2), 74.9 (PhCH2), 73.3
(PhCH2), 73.3 (PhCH2), 70.7 (C-5), 67.9 (C-6), 60.47 (OCH2), 58.5
(cyclopropyl-1), 21.0 (cyclopropyl-2), 15.5 (cyclopropyl-3), 14.2
(CH3). HRMS calcd for C40H44O8 Na [M+Na]+: 675.2933. Found:
675.2942.
1.5. 1-Phenylcyclopropyl 2,3,4,6-tetra-O-benzyl-b-D-
glucopyranoside 5c
To a stirring solution of 2,3,4,6-tetra-O-benzyl-b-D-glucopyran-
osyl trichloroacetimidate17 (1.54 g, 2.25 mmol) in anhydrous
dichloromethane (11 mL) was added 1-phenyl-1-cyclopropanol16
(155 mg, 1.15 mmol). The solution was cooled to 0 °C and boron
tions: mp 83–86 °C, Rf 0.46 (20% EtOAc–hexanes), ½a D
ꢂ
+51.8 (c 1.0,
dichloromethane), 1H NMR d 7.34–7.11 (m, 20H, Ph-H), 4.95, 4.79
(ABq, 2H, J = 10.7, PhCH2), 5.09 (d, 1H, J1,2 = 3.7, H-1), 4.82, 4.45
(ABq, 2H, J = 10.5, PhCH2), 4.73, 4.64 (ABq, 2H, J = 12.2, PhCH2),
4.62, 4.45 (ABq, 2H, J = 12.0, PhCH2), 3.92 (dd, 1H, J3,2 = 9.7,
trifluoride diethyl etherate (150 lL) was added under argon. The
reaction mixture was allowed to warm to rt, and stirred for 2 h,
after which another 155 mg of 1-phenyl-1-cyclopropanol was
added. The reaction mixture was again cooled to 0 °C and addi-
0
J3,4 = 9.1, H-3), 3.85 (ddd, 1H, J5,4 = 10.0, J5,6 = 3.5, J5,6 = 2.2, H-5),
tional boron trifluoride diethyl etherate (150 lL) was added. After
0
0
3.72 (dd, 1H, J6,5 = 3.5, J6,6 = 10.5, H-6), 3.60 (dd, 1H, J6 ,5 = 2.2,
2 h the reaction was quenched with 3 mL saturated sodium car-
bonate solution. The organic layer was separated and dried over
MgSO4 then concentrated to yield a viscous brown oil which was
purified by flash chromatography (1:2:97 triethylamine–EtOAc–
hexanes) to yield a yellow oil (0.59 g, 40%): Rf 0.72 (25% EtOAc–
J6,6 = 10.5, H-60), 3.63 (dd, 1H, J4,3 = 9.1, J4,5 = 10.0, H-4), 3.51 (dd,
0
1H, J2,1 = 3.7, J2,3 = 9.7, H-2), 1.45 (br s, 3H, CH3), 1.07 (m, 1H, cyclo-
propyl), 0.75 (m, 1H, cyclopropyl), 0.41 (m, 2H, cyclopropyl); 13C
NMR d 138.6, 138.0, 137.9, 137.7 (Ph-ipso’s), 128.2–127.2, 20C,
overlapped (Ph-CH’s), 95.9 (C-1), 81.9 (C-3), 79.5 (C-2), 77.7
(C-4), 75.4, 74.8, 73.1, 73.3 (PhCH2’s), 70.1 (C-5), 68.4 (C-6), 58.5
(cyclopropyl), 22.1 (CH3). 13.8 (cyclopropyl), 12.3 (cyclopropyl).
hexanes), ½a D
ꢂ
+11.8 (c 1.0, chloroform), 1H NMR d 7.48–7.11 (m,
25H, Ph-H), 4.92, 4.73 (ABq, 2H, J = 10.8, PhCH2), 4.88, 4.76 (ABq,
2H, J = 10.4, PhCH2), 4.79, 4.54 (ABq, 2H, J = 11.2, PhCH2), 4.59 (d,
1H, J1,2 = 8.1, H-1), 4.53, 4.43 (ABq, 2H, J = 12.3, PhCH2), 3.61 (m,
1H, H-6), 3.58 (m, 1H, J4,3 = ND, J4,5 = 9.8, H-4), 3.54 (m, 1H, H-60),
3.58 (m, 1H, J3,2 = 8.1, J3,4 = ND, H-3), 3.43 (dd, 1H, J2,1 = 8.1,
J2,3 = 9.3, H-2), 3.30 (m, 1H, H-5), 1.68 (m, 1H, Jgem = 11.6, Jvic = 6.9,
5.2, cyclopropyl-2a), 1.32 (m, 1H, cyclopropyl-3a), 1.04 (m, 1H,
cyclopropyl-2b), 0.93 (m, 1H, cyclopropyl-3b); 13C NMR d 141.0
(CP-Ph ipso), 138.4, 2 ꢃ 138.2, 138.0 (Ph-CH2ipso), 128.8–128.2
(25C, Ph-CH), 102.0 (C-1), 84.8 (C-3), 82.1 (C-2), 77.7 (C-4), 75.4,
74.8, 74.7 (PhCH2’s), 74.6 (C-5), 73.3 (PhCH2), 68.7(C-6), 63.7
(cyclopropyl-1), 14.6 (cyclopropyl-2), 14.4 (cyclopropyl-3).
HRMS calcd for
612.3325.
C
38H46NO6 [M+NH4]+: 612.3309. Found:
1.4. 1-(2-Ethoxycarbonylcyclopropyl) 2,3,4,6-tetra-O-benzyl-a-
D-glucopyranoside 5d
To a stirring solution of vinyl 2,3,4,6-tetra-O-benzyl-a-D-gluco-
pyranoside (500 mg, 0.89 mmol) and rhodium(II) acetate dimer
(39 mg, 0.088 mmol) in dichloroethane (5 mL) was added a solu-
tion of ethyl diazoacetate (93.5 lL, 1.5 equiv) in dichloroethane
(1 mL) over the course of 1 h at 60 °C with stirring. The reaction
was stirred for 4 h at 60 °C, then concentrated to an oil that puri-
fied by flash chromatography; yield, 205 mg (35%). The carboeth-
oxy-substituted was obtained as an inseparable mixture of
diastereomers: Rf 0.3 (25% EtOAc–hexanes), 1H NMR (isomer A) d
7.35–7.10 (m, both diastereomers, Ph-H), 4.94, 4.79 (ABq, 2H,
J = 10.9, PhCH2), 4.82, 4.45 (ABq, 2H, J = 10.8, PhCH2), 4.82 (d, 1H,
J1,2 = 3.7, H-1), 4.78, 4.60 (ABq, 2H, J = 12.1, PhCH2), 4.61, 4.45
(ABq, 2H, J = 12.0, PhCH2), 3.89 (dd, 1H, J3,2 = 9.7, J3,4 = 8.8, H-3),
3.82 (ddd, 1H, J = 2.0, 4.3, 6.9, cyclopropyl-1), 3.81 (m, 1H, H-5),
3.66 (m, 1H, H-4), 3.76–3.62(m, 2H, H-6, H-60), 3.54 (dd, 1H,
J2,1 = 3.7, J2,3 = 9.7, H-2), 4.11 (q, 2H, Jvic = 7.2, OCH2), 1.73 (ddd,
1H, J = 2.0, 6.1, 9.6, cyclopropyl-2), 1.44 (m, 1H, cyclopropyl-3a),
1.30 (m, 1H, cyclopropyl-3b), 1.27 (t, 3H, Jvic = 7.2, CH3); 13C NMR
d 138.4, 137.8, 137.6, 137.48 (Ph-ipso’s), 128.3–127.3, (19 reso-
nances, overlapped C for both diastereomers, Ph-CH), 97.8 (C-1),
81.7 (C-3), 79.4 (C-2), 77.2 (C-4), 75.6, 74.9, 73.5, 73.4 (PhCH2’s),
70.6 (C-5), 67.9 (C-6), 60.5 (OCH2), 57.8 (cyclopropyl-1), 20.6
(cyclopropyl-2), 15.5 (cyclopropyl-3), 14.1 (CH3);(isomer B) d
7.35–7.10 (m, both diastereomers, Ph-H), 4.95, 4.79 (ABq, 2H,
J = 10.8, PhCH2), 4.82, 4.45 (ABq, 2H, J = 10.8, PhCH2), 4.84 (d, 1H,
J1,2 = 3.7, J2,3 = 9.7, H-1), 4.79, 4.60 (ABq, 2H, J = 12.1, PhCH2),
4.62, 4.46 (ABq, 2H, J = 12.2, PhCH2), 3.89 (dd, 1H, J3,2 = 9.7,
J3,4 = 8.7, H-3), 3.74 (m, 1H, H-5), 3.69 (ddd, 1H, cyclopropyl-1),
3.67 (m, 1H, H-4), 3.76–3.62(m, 2H, H-6, H-60), 3.55 (dd, 1H,
J2,1 = 3.7, J2,3 = 9.7, H-2), 4.09 (q, 2H, Jvic = 7.2, OCH2), 1.97 (ddd,
1H, J = 2.2, 6.1, 9.8, cyclopropyl-2), 1.23 (t, 3H, Jvic = 7.2, CH3),
1.21(m, 1H, cyclopropyl-3a), 1.14 (m, 1H, cyclopropyl-3b); 13C
HRMS calcd for
679.3036.
C
43H44NaO6 [M+Na]+: 679.3037. Found:
1.6. Methyl 3-(2,3,4,6-tetra-O-benzyl-a/b-D-glucopyranosyloxy)-
(S)-2-(9-fluorenyl-methoxycarbonylamino)-propanoate 7a
From 5b: To a stirring solution of cyclopropyl glycoside 5b
(59 mg, 0.1 mmol) in anhydrous dichloromethane (2 mL) was
added Fmoc-protected serine methyl ester 6a (17 mg, 0.05 mmol)
and the solution was flushed with argon and cooled to ꢀ78 °C. Tri-
methylsilyl trifluoromethanesulfonate (0.01 mL, 0.05 mmol) was
added and the reaction mixture was allowed to warm to rt. After
2 h, additional 6a (17 mg, 0.05 mmol) and TMS triflate (0.01 mL,
0.05 mmol) were added at ꢀ78 °C and the reaction was stirred
for an additional 2 h. Saturated sodium carbonate solution was
added followed by diethyl ether (10 mL). The organic phase was
separated, dried (Na2SO4) and concentrated to an oil that was puri-
fied by flash chromatography using 30% EtOAc–hexanes to give
unseparated anomers of 7a (51 mg, 59%, 2:1
a/b): Rf 0.37 (30%
EtOAc–hexanes), 1H NMR (
a
anomer) d 7.74–7.10 (m, 28H, Ph),
6.08 (m, 1H, J = 8.7, NH), 4.96, 4.82 (ABq, 2H, J = 10.8, PhCH2),
4.82, 4.47 (ABq, 2H, J = 10.6, PhCH2), 4.76 (d, 1H, J1,2 = 3.5, H-1),
4.71, 4.60 (ABq, 2H, J 12.0, PhCH2), 4.57, 4.45 (ABq, 2H, J = 12.3,
PhCH2), 4.56 (dd, 1H, J = 3.4, 3.7, CHN), 4.42–4.25 (m, 2H, OCOCH2),
4.22 (m, 1H, CHCH2O), 4.12 (dd, 1H, J = 3.7, 10.7, CHO), 3.93 (dd,
1H, J3,2 = 9.7, J3,4 = 8.8, H-3), 3.87 (dd, 1H, J = 3.4, 10.7, CHO), 3.73
(m, 1H, J5,4 = 10.1, H-5), 3.70 (s, 3H, OCH3), 3.69 (m, 2H, H-6,60),
3.63 (dd, 1H, J4,3 = 8.8, J4,5 = 10.1, H-4), 3.56 (dd, 1H, J2,3 = 9.7,

C. Scholl et al. / Carbohydrate Research 356 (2012) 288–294
293
J3,4 = 8.8 H-2); 13C NMR (
a
anomer) d F = (fluorenyl) 170.2 (OC@O),
F8a, F9a, 141.0 F4a, F4b, 138.4–137.5 (both isomers, 8C, Ph-ipso),
128.8 (F2, F7), 128.2–127.4 (both isomers, Ph-CH2 + F3,6), 124.9
(F1, F8), 119.7 (F4, F5), 97.95 (C-1), 81.6 (C-3), 79.2 (C-2), 77.4
(C-4), 75.6 (CHO), 75.4, 75.1, 73.4, 73.0 (4C, PhCH2’s), 70.8 (C-5),
68.1 (C-6), 67.0 (OCOCH2), 58.8 (CHN), 52.4 (OCH3), 47.0 (CHCH2),
1H NMR (b anomer) d 7.73–7.10 (m, 28H, Ph), 5.82 (m, 1H, J = 8.6,
NH), 4.90, 4.79 (ABq, 2H, PhCH2), 4.88, 4.71 (ABq, 2H, PhCH2), 4.79,
4.52 (ABq, 2H, PhCH2), 4.53, 4.46 (ABq, 2H, PhCH2), 4.43 (m, 1H,
J = 6.4, CH3CHO), 4.42 (d, 1H, J1,2 = 8.0, H-1), 4.40 (m, 1H, CHN),
4.39 (m, 2H, OCOCH2), 4.23 (m, 1H, J = 7.0, CHCH2O), 3.76 (s, 3H,
OCH3), 3.65 (m, 3H, H-3, H-4, H-5), 3.6 (m, 2H, H-6, 60), 3.43 (dd,
1H, H-2) 1.31 (d, 3H, CH3CH); 13C NMR d 138.4–137.5 (8C, Ph);
13C NMR (b anomer) d 170.5 (OC@O), 156.4 (NC@O), 143.66,
143.45 F8a, F9a, 141.0, 141.0 F4a, F4b, 138.4–137.5 (both isomers,
8C, Ph-ipso), 128.8 (F2, F7), 128.2–127.4 (both isomers, Ph-
CH2 + F3,6), 124.9 (F1, F8), 119.7 (F4, F5), 101.4 (C-1), 84.4 (C-3),
81.6 (C-2), 77.3 (C-4), 75.5 (PhCH2), 74.9 (PhCH2), 74.9 (PhCH2),
74.6 (CHO), 74.5 (C-5), 73.3 (PhCH2), 68.6 (C-6), 67.1 (OCOCH2),
58.6 (CHN), 52.3 (OCH3), 47.0 (CHCH2). HRMS calcd for
155.8 (NC@O), 143.6 (F8a,9a), 141.0 (F4a,4b), 138.4–137.5 (both
isomers, 8C, Ph-ipso), 128.2–127.4 (both isomers, Ph-CH2 + F3,6),
126.9 (F2,7), 125.0 (F1,8), 119.7 (F4,5), 98.6 (C-1), 81.6 (C-3), 79.7
(C-2), 77.3 (C-4), 75.6, 75.1, 73.4, 73.0 (4C, PhCH2’s), 70.8 (C-5),
69.9 (CH2O), 68.2 (C-6), 67.1 (OCOCH2), 54.5 (CHN), 52.6 (OCH3),
47.0 (CHCH2).
1H NMR (b anomer) d 7.74–7.10 (m, 28H, Ph), 5.84 (m, 1H,
J = 7.9, NH), 4.93, 4.82 (ABq, 2H, J = 10.8, PhCH2), 4.88, 4.73 (ABq,
2H, J = 11.0, PhCH2), 4.81, 4.53 (ABq, 2H, J 10.8, PhCH2), 4.59, 4.26
(ABq, 2H, J = 12.2, PhCH2), 4.55 (m, 1H, J = 3.4, CHN), 4.42–4.25
(m, 2H, OCOCH2), 4.36 (d, 1H, J1,2 = 7.8, H-1), 4.19 (m, 1H, CHCH2O),
4.35 (m, 1H, J = 3.5, CHO), 3.93 (m, 1H, H-3), 3.89 (dd, 1H, J = 3.4,
10.7, CHO), 3.42 (m, 1H, H-5), 3.76 (s, 3H, OCH3), 3.69 (m, 2H, H-
6,60), 3.63 (m, 1H, H-4), 3.45 (m, 1H, H-2); 13C NMR (b anomer) d,
F = (fluorenyl), 170.1 (OC@O), 155.7 (NC@O), 143.5 (F8a,9a),
141.0 (F4a,4b), 138.4–137.5 (both isomers, 8C, Ph-ipso), 128.2–
127.4 (both isomers, Ph-CH2 + F3,6), 126.9 (F2,7), 124.9 (F1,8),
119.7 (F4,5), 103.8 (C-1), 84.5 (C-3), 81.6 (C-2), 77.5 (C-4), 75.6
(PhCH2), 74.9 (PhCH2), 74.8 (C-5), 73.4 (PhCH2), 73.0 (PhCH2),
69.8 (CH2O), 68.4 (C-6), 67.2 (OCOCH2), 54.5 (CHN), 52.6 (OCH3),
47.0 (CHCH2). HRMS calcd for C53H54NO10 [M+H]+: 864.3748.
Found: 864.3748.
From5c: To a stirring solution of 5c (85 mg, 0.13 mmol) in anhy-
drous dichloromethane (2.5 mL) was added Fmoc-protected serine
methyl ester 6a (25 mg, 0.073 mmol). The solution was flushed
with argon and cooled to ꢀ78 °C. Trimethylsilyl trifluoromethane-
sulfonate (0.015 mL, 0.075 mmol) was added and the reaction mix-
ture was allowed to warm to room temperature. After 2 h,
additional 6a (25 mg, 0.073 mmol) and TMS triflate (0.015 mL,
0.075 mmol) were added at ꢀ78 °C and the reaction was stirred
for an additional 2 h. Saturated sodium carbonate solution was
added followed by diethyl ether (10 mL). The organic phase was
separated, dried (Na2SO4) and concentrated to an oil that was puri-
fied by flash chromatography using 30% EtOAc–hexanes to give
C
54H56NO10 [M+H]+: 878.3904. Found: 878.3865.
From5c: To a stirring solution of 5c (85 mg, 0.13 mmol) in anhy-
drous dichloromethane (2.5 mL) was added Fmoc-protected threo-
nine methyl ester 6a (28 mg, 0.079 mmol). The solution was
flushed with argon and cooled to ꢀ78 °C. Trimethylsilyl trifluoro-
methanesulfonate (0.015 mL, 0.075 mmol) was added and the
reaction mixture was allowed to warm to room temperature. After
2 h, additional 6a (28 mg, 0.079 mmol) and TMS triflate (0.015 mL,
0.075 mmol) were added at ꢀ78 °C and the reaction was stirred for
an additional 2 h. Saturated sodium carbonate solution was added
followed by diethyl ether (10 mL). The organic phase was sepa-
rated, dried (Na2SO4) and concentrated to an oil that was purified
by flash chromatography using 30% EtOAc–hexanes to give insep-
arable anomers of 7a (35 mg, 39%, 1.4:1 a/b).
1.8. Methyl 2,3,4-tri-O-benzyl-6-O-(2,3,4,6-tetra-O-benzyl-
a/b-D-
inseparable anomers of 7a (116 mg, 90%, 2.4:1
a
/b).
glucopyranosyl)-
a-D
-glucopyranoside 926,30
1.7. Methyl (R)-3-(2,3,4,6-tetra-O-benzyl- /b-
syloxy)-(S)-2-(9-fluorenyl-methoxycarbonylamino)butanoate 7b
a
D
-glucopyrano-
To a stirring solution of methyl 2,3,4-tri-O-benzyl-
ranoside 828,29 (35 mg, 0.075 mmol) and 1-phenylcyclopropyl
2,3,4,6-tetra-O-benzyl- -glycopyranoside 5c (0.042 g, 0.064
a-D-glucopy-
a
-D
From 5b: To a stirring solution of cyclopropyl glycoside 5b
(120 mg, 0.2 mmol) in anhydrous dichloromethane (4 mL) was
added Fmoc-protected threonine methyl ester 6b (36 mg,
0.1 mmol) and the solution was flushed with argon and cooled to
ꢀ78 °C. Trimethylsilyl trifluoromethanesulfonate (0.02 mL,
0.1 mmol) was added and the reaction mixture was allowed to
warm to rt. After 2 h, an additional 6b (36 mg, 0.1 mmol) and
TMS triflate (0.02 mL, 0.1 mmol) were added at ꢀ78 °C and the
reactions was stirred for an additional 2 h. Saturated sodium car-
bonate solution was added followed by dichloromethane (5 mL).
The organic phase was separated, dried (Na2SO4) and concentrated
to an oil that was purified by flash chromatography using a gradi-
ent of 10% EtOAc–hexanes to 30% EtOAc–hexanes to give unsepa-
mmol) in anhydrous dichloromethane (2 mL) was added trimeth-
ylsilyl trifluoromethanesulfonate (0.01 mL, 0.05 mmol) under ar-
gon at 0 °C. The reaction mixture was allowed to warm to room
temperature and stirred for 2 h, after which some more of 8
(35 mg, 0.075 mmol) in dichloromethane was added, and the reac-
tion mixture was again cooled to 0 °C and more trimethylsilyl tri-
fluoromethanesulfonate was added (0.01 mL, 0.05 mmol). The
reaction mixture was allowed to warm to room temperature and
stirred for another 2 h. Saturated sodium carbonate solution
(1 mL) was then added, the mixture was diluted with 10 mL
dichloromethane, and the organic layer was separated, dried
(MgSO4), filtered, and concentrated under reduced pressure to a
brown oil (0.086 g) that was purified by flash chromatography on
silica gel to give 9 as a mixture of anomers; yield, 32 mg (51%,
rated anomers of 7a (100 mg, 58%, 2:1
a/b): Rf 0.42 (30% EtOAc–
hexanes), 1H NMR (
a
anomer) d 7.70–7.10 (m, 28H, Ph), 5.98 (m,
3.8:1 a a anomer): d
/b): Rf 0.63 (30% EtOAc–hexanes), 1H NMR (
1H, J = 8.1, NH), 4.96, 4.84 (ABq, 2H, PhCH2), 4.89 (d, 1H, J1,2 = 3.7,
H-1), 4.81, 4.44 (ABq, 2H, PhCH2), 4.61, 4.60 (ABq, 2H, PhCH2),
4.57, 4.45 (ABq, 2H, PhCH2), 4.43 (m, 2H, OCOCH2), 4.38 (m, 1H,
J = 6.4, CH3CHO), 4.34 (m, 1H, CHN), 4.23 (m, 1H, J = 7.0, CHCH2O),
3.95 (m, 1H, J3,2 = 9.8, J3,4 = 9.2, H-3), 3.85 (m, 1H, J5,6 = 3.4, H-5),
7.36–7.08 (m, 35H, Ph-H), 4.97 (d, 1H, J = 3.6, H-1), 4.95, 4.81
(ABq, 2H, PhCH2), 4.94, 4.77 (ABq, 2H, PhCH2), 4.91, 4.64 (ABq,
2H, PhCH2), 4.82, 4.45 (ABq, 2H, PhCH2), 4.71, 4.57 (ABq, 2H,
PhCH2), 4.66 (ABq, 2H, tight pair, PhCH2), 4.57, 4.42 (ABq, 2H,
PhCH2), 4.54 (d, 1H, J = 3.9, H-10), 3.98 (m, 1H, H-30), 3.95 (m, 1H,
0
0
0
0
3.75 (m, 1H, J6,6 = 10.6, H-6), 3.70 (s, 3H, OCH3), 3.67 (m, 1H,
H-3), 3.82–3.49 (m, 6H, H-5 , H-5, H-6a, H-6b, H-6a , H-6b ), 3.65
(m, 1H, H-40), 3.62 (m, 1H, H-4), 3.54 (m, 1H, H-2), 3.44 (m, 1H,
H-20), 3.35 (s, 3H, CH3O). HRMS calcd for C62H66O11 [M+Na]+:
1009.4503. Found: 1009.4487.
J4,3 = 9.2, J4,5 = 9.8, H-4), 3.60 (m, 1H, H-60), 3.50 (dd, 1H, J2,1 = 3.7,
J2,3 = 9.8, H-2), 1.31 (d, 3H, Jvic = 6.4, CH3CH); 13C NMR (
a
anomer)
d, F = (fluorenyl) d 170.7 (OC@O), 156.4 (NC@O), 143.62, 143.50

294
C. Scholl et al. / Carbohydrate Research 356 (2012) 288–294
1.9. 2-Deoxy-6-O-(2,3,4,6-tetra-O-benzyl-
a
-D
-glucopyranosyl)-
(Summer Research Fellowship for Christopher Cummings), and
3-O-(2,2,2-trichloroethoxycarbonyl)-2-(2,2,2-trichloroethoxy-
carbonylamino)- -glucopyranose 11
Villanova University for financial support of this work. We also
thank Mr. Craig Johnson of GlaxoSmithKline Biologicals for the
preparation of compound 10, and Dr. Charles DeBrosse of Temple
University for 2D NMR analysis of compound 11.
a-D
To a stirring solution of benzyl 2-deoxy-3-O-(2,2,2-trichloroeth-
oxycarbonyl)-2-(2,2,2-trichloroethoxycarbonylamino)-b- -gluco-
pyranoside 1031,32 (100 mg, 0.16 mmol. and 1-methylcyclopropyl
2,3,4,6-tetra-O-benzyl- -glucopyranoside 5b (120 mg, 0.20
mmol) in 5 mL methylene chloride was added trimethylsilyl trifluo-
romethanesulfonate (35 L, 0.19 mol) under argon at 0 °C. The reac-
D
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a
-D
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J5,4 = 10.0, J5,6a = 4.2, J5,6b = 2.1, H-50), 3.77 (dd, 1H, J6a,5
=
0
00
0.9J6a,6b = 7.9, H-6b), 3.67 (dd, 1H, J6 a,5 = 4.2, J6 a,6 b = 10.8, H-6a0),
0
0
0
0
3.64 (m, 1H, H-4), 3.60 (t, 1H, J4 ,3 = 9.3 J4 ,5 = 10.0, H-40 3.60 (dd,
0
0
0
0
1H, J6 b,5 = 2.1, J6 a,6 b = 10.8, H-6b0), 3.57 (dd, 1H, J2,1 = 3.8,
J2,3 = 9.7, H-20); 13C NMR d 154.2 (C3 C@O), 153.4 (C@O), 138.9,
138.2, 137.9, 137.7 (ipso’s), 129.0–127.9 (20C, Ph), 99.4 (C-1), 96.9
(C-10), 95.5 (CCl3), 94.3 (CCl3), 81.9 (C30), 77.8 (C20), 77.2(C-40),
76.9 (CH2-Troc), 75.7 (PhCH2), 75.1 (PhCH2), 74.8 (C5), 74.6 (C3),
73.7 (PhCH2), 73.4 (PhCH2), 73.2 (C3), 71.8 (C4), 71.4 (C50), 68.2
(C60), 64.7 (C6), 50.4 (C2). ESMS calcd for C46H50NO14Cl6 [M+H]+:
1050.14. Found: 1050.1.
0
0
0
0
31. Johnson, D. A.; Keegan, D. S.; Sowell, C. G.; Livesay, M. T.; Johnson, C. L.;
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Acknowledgements
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The authors thank the Petroleum Research Fund, administered
by the American Chemical Society, GlaxoSmithKline Biologicals