An efficient synthesis of N-allylglycosylamides from unprotected carbohydrates

Article abstract of DOI:10.1021/jo9522522

Synthetic, multivalent, carbohydrato assemblies are important tools in studying the avidity of many naturally occuring lectins for their ligands. This report details a simple, high-yielding three-step procedure to convert unprotected carbohydrates into N-allylglycosides. This method compliments the reductive amination procedure but allows the reducing-end pyranose ring to remain intact. No carbohydrate protecting groups are needed, and the resulting N-allylglycosylamide can be easily linked to other molecules. Two examples of analogs of silyl Lewis(x) and sulfo Lewis(X) have been derivatized by this process.

Full text of DOI:10.1021/jo9522522

J . Org. Chem. 1996, 61, 3417-3422
3417
An Efficien t Syn th esis of N-Allylglycosyla m id es fr om Un p r otected
Ca r boh yd r a tes
Wayne Spevak,† Falguni Dasgupta,‡ Christopher J . Hobbs,† and J on O. Nagy*,†
Center for Advanced Materials, Lawrence Berkeley National Laboratory, Berkeley, California 94720, and
Glycomed, Inc., Atlantic Avenue, Alameda, California 94501
Received December 21, 1995X
Synthetic, multivalent, carbohydrate assemblies are important tools in studying the avidity of many
naturally occuring lectins for their ligands. This report details a simple, high-yielding three-step
procedure to convert unprotected carbohydrates into N-allylglycosides. This method compliments
the reductive amination procedure but allows the reducing-end pyranose ring to remain intact.
No carbohydrate protecting groups are needed, and the resulting N-allylglycosylamide can be easily
linked to other molecules. Two examples of analogs of silyl Lewisx and sulfo Lewisx have been
derivatized by this process.
Sch em e 1
In tr od u ction
Carbohydrate-lectin interactions play a key role in
biological processes such as cell recognition during
pathogenic infection,1-3 control of differentiation,4 clear-
ance of tumor cells,5 and inflammation.6 Recently, lectin-
mediated carbohydrate binding has been shown to stimu-
late signal transduction.7,8 In general, however, the
binding strength of lectins for carbohydrates is low
compared to other biological recognition events.9 Nature
quite often employs a strategy to improve binding by
expressing many copies of a carbohydrate on a single
scaffold. In this manner, multivalent forms of the
carbohydrate bind through avidity, orders of magnitude
higher. To study these important biological interactions,
synthetic particles that incorporate known amounts of
specific oligosaccharides must be prepared. Because the
desired carbohydrate may be extremely expensive or
available in only limited supply, the linking chemistry
must be simple and efficient. In this paper, we present
a nonreductive method that compliments the reductive
amination reaction for introducing a linking handle on
the glycosidic position of a carbohydrate.
explored extending this work to amines containing
functionality. We have developed a general three-step
strategy to introduce an N-acetylallylamine group onto
oligosaccharides (Scheme 1).
In this method, unprotected oligosaccharides are dis-
solved in neat allylamine. In most cases the carbohy-
drate is readily soluble in this solvent at ambient
temperature. However, if after several hours the starting
material is incompletely dissolved, some water may be
added. This tends to lengthen the reaction time but has
no adverse effect on yield.
The initial step in this transformation is the attack of
allylamine on the anomeric hydroxyl group. Due to the
weak anomeric effect of the nitrogen atom, only the
â-glucopyranosylamine is obtained.11 However, heating
the solution leads to the formation of mixtures of R and
â anomers and other side products. The excess of amine
inhibits the formation of N,N-diglycosylamines. A num-
ber of examples of N-allyl glycosides have been reported
in the literature.12-15 In one report, the N-allyl glycoside
is directly isolated;15 in all other cases, the amine is
immediately converted to a urea prior to isolation and
characterization. In our hands, we have found that the
carbohydrate aminals easily hydrolyze back to the parent
sugar, lowering the isolated yields. However, immediate
acylation gives a stable product. The following table
shows representative examples of carbohydrates that
have been converted into the peracetylated N-allylgly-
cosylamides (1-8). The N-acetate group in nearly all
cases displays restricted rotation, giving rise to multiplic-
Resu lts a n d Discu ssion
Inspired by the facile method of Lockhoff10 for the
formation of long chain glycosylamide glycolipids, we
* To whom correspondence should be addressed. Tel.: (510) 486-
4964. E-mail: jonagy@lbl.gov.
† Center for Advanced Materials.
‡ Glycomed, Inc.
X Abstract published in Advance ACS Abstracts, May 1, 1996.
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S0022-3263(95)02252-3 CCC: $12.00 © 1996 American Chemical Society

3418 J . Org. Chem., Vol. 61, No. 10, 1996
Ta ble 1. Selected Exa m p les of Ca r boh yd r a tes Con ver ted to N-Allylglycosa m id es
Spevak et al.
ity of signals in the carbon and proton NMR spectra.
Heating of the material to at least 85 °C in DMSO shows
peak coalescence. This phenomenon was also observed
for the long chain and aryl glycosyl amides.10,16
The reaction of 3′-acetic acid-Gal-â-1,4-[Fuc R-1,3]Glc
in this procedure followed by methanol treatment gives
a mixture of the methyl ester (7) and various lactones.17
Compound 7 can be purified from the mix in 55% yield;
however, directly treating the crude mixture with sodium
methoxide18 (Zemple´n conditions) converts the ester and
lactones directly to compound 15 in 76% overall yield.
The other peracetylated glycosides are likewise treated
to give deprotected N-allyl glycosylamides (Table 1).
An allylic group at the glycosyl position is an extremely
versatile functionality serving to both protect the ano-
meric position, allowing modifications to other parts of
the oligosaccharide, and act as a ready handle for specific
linking reactions.19-23
There are many ways to introduce functionality to the
reducing end of oligosaccharides. In typical carbohydrate
synthesis the standard method for glycosyl functional-
ization involves protection of the hydroxyl groups and
activation of the glycosyl position. This is usually ac-
complished with concomitant generation of strong acids
(e.g., glycosyl halides)24 or by the use of strong bases (as
(19) Roy, R.; Tropper, F. D. J . Chem. Soc., Chem. Commun. 1988,
1058.
(20) Roy, R.; Laferriere, C. A. Carbohydr. Res. 1988, 177, C1.
(21) Allanson, N. M.; Davidson, A. H.; Martin, F. M. Tetrahedron
Lett. 1993, 34, 3945.
(22) Kallin, E.; Lo¨nn, H.; Norberg, T.; Elofsson, M. J . Carbohydr.
Chem. 1989, 8, 597.
(16) Vigdorchik, M. M.; Kostyuchenko, N. P.; Olad’ko, R. P.; Mosina,
G. S.; Sheinker, Yu.N.; Suvorov, N. L. J . Org. Chem. USSR (Engl.
Transl.) 1973, 9, 617.
(17) Danishefsky, S. J .; Gervay, J .; Peterson, J . M.; McDonald, F.
E.; Koseki, K.; Griffith, D. A.; Oriyama, T. Marsden, S. P. J . Am. Chem.
Soc. 1995, 117, 1940.
(18) Peters, S.; Bielfeldt, T.; Meldal, M.; Bock, K.; Paulsen, H. J .
Chem Soc., Perkin Trans. 1 1992, 1163.
(23) Spevak, W.; Nagy, J . O.; Tropper, F. D. Manuscript in prepara-
tion.

Synthesis of N-Allylglycosylamides
J . Org. Chem., Vol. 61, No. 10, 1996 3419
in acetamide formation, the Schmidt reaction).25 Ex-
tremely sensitive carbohydrate linkages, as in fucosylo-
ligosaccharides, can be intolerant of these conditions. For
large oligosaccharides or natural product samples avail-
able only in minute quanitities the use of complicated
protection/deprotection chemistry is problematic or inef-
ficient. Further complications can occur when N-acetyl
groups are present in the 2-position. The formation of
oxazolines as byproducts is common.26
This methodology has enabled us to take oligosaccha-
rides from synthetic and natural sources and prepare
them for multimerization. Compounds 15 and 16 are
prepared from 3′-(acetic acid)- and 3′-sulfo-Lewis X
analogs which are implicated as antagonists toward
selectins in the inflammation response.32 Multivalent
particles containing these linked analogs show extremely
potent P-selectin inhibition33 and will be the subject of
future reports with L- and E-selectin.
Alternatively, and in a more direct manner, there are
several ways to introduce linking groups to an unpro-
tected oligosaccharide’s glycosidic position. This can be
accomplished by reductive amination if the pyranose or
furanose ring of the reducing end carbohydrate is not
important. However, when the integrity of this ring is
necessary for biological activity, strategies employing the
formation of an amine glycoside are used. Owing to the
greater nucleophilicity of the nitrogen atom in unsubsti-
tuted glycosylamines, this group can be selectivly de-
rivatized.27 Glycosylamines can be prepared by treat-
ment of the carbohydrate with aqueous ammonium
carbonate28 (the Kochetkov reaction) or, alternatively,
Exp er im en ta l Section
Gen er a l P r oced u r es. Materials were obtained from com-
mercial suppliers: D-glucose (Sigma), D-lactose (Malinckrodt),
N-acetyl-D-glycosamine (U.S. Biochemicals), L-fucose (Aldrich),
and GalR-1,3-Galâ-1,4-GlcNAc (Dextra Labs Ltd.). 3′-Acetic
acid- and 3′-sulfo-Galâ-1,4 (FucR-1,3)Glu were gifts from
Glycomed Inc. (Alameda). Tri-N-acetyl-chitotriose was ob-
tained from hydrolysis and acelyation of crude chitosan34 and
was used without further purification. Allylamine was ob-
tained from Aldrich and is classified as a highly toxic material.
Due to it’s high volatility, evaporation and all other handling
should be carried out in an efficient fume hood. Deionized
water was used in all manipulations. The silica gel used in
column chromatography was Kieselgel 60 (Merck, 230-400).
Thin layer chromatography (TLC) was performed using An-
altech silica gel GHLF coated on glass plates. TLC plates were
visualized using molybdate stain (72 g of ammonium molyb-
date, 3 g of ceric sulfate, 50 mL of concentrated sulfuric acid,
and 250 mL of water). Melting points were determined in
capillaries and are uncorrected. 1H NMR spectra were deter-
mined at either 400, 500, or 200 MHz as indicated. Chemical
shifts are reported as parts per million (δ), positive values
indicating shifts downfield of tetramethylsilane. 1H NMR
spectra determined in D2O and DMSO-d6 are reported relative
to 4.61 and 2.49 ppm, respectively. The 1H NMR spectra
determined in CDCl3 are reported relative to 7.25 ppm. The
1H NMR spectra determined in CD3OD are reported relative
to the HOD signal at 4.63 ppm. 1H NMR data are tabulated
in order: multiplicity (s, singlet; d, doublet; t, triplet; q,
quartet; m, multiplet; br, broad), number of protons, and
coupling constant(s) in Hz. 13C NMR spectra were proton
decoupled and measured at either 100 or 125 MHz. Chemical
shifts are reported relative to the central peak of CDCl3 at
77.0 ppm, the central peak of CD3OD at 49.0 ppm, or the
central peak of DMSO-d6 at 39.5 ppm. All high-temperature
NMR experiments were performed on a 400 MHz instrument.
Fast atom bombardment (FAB+) mass spectra and electron
ionization (EI+) mass spectra were recorded at the UC
Berkeley Mass Spectral Laboratory. Elemental analyses were
performed by the microanalytical laboratory operated by the
College of Chemistry at the University of California, Berkeley.
Gen er a l P r oced u r e for th e P r ep a r a tion of P er a cetyl-
a ted â-NAc-a llyl Glycosid es fr om F r ee Su ga r s. Neat
allylamine was added to the carbohydrate containing a free
reducing end to give a 0.5-0.1 M solution. The reaction was
stoppered and stirred at ambient temperature for not less than
48 h. Small quantities of water can be added if the entire
amount of carbohydrate does not dissolve after 6 h of stirring.
Heating of the reaction is not recommended, since this leads
to production of significant quantities of impurities. The initial
allylamine glycoside product was unstable to thin-layer silica
gel chromatography; therefore, this technique cannot be used
to measure the progress of the reaction. Typically, a small
aliquot was removed from the reaction, peracetylated (as
described below), and compared to a sample of the starting
sugar that has been peracetylated. The peracetylated glyco-
sylamide product was always seen as a slightly more polar
anhydrous,27 methanolic,29 or aqueous30 ammonia.
A
recent report of a large nunber of mono- and oligosac-
charides subjected to the Kochetkov reaction has ap-
peared.31
There are various drawbacks with these methods.
Glycosylamines are not stable compounds.30,31 Hydrolysis
in neutral or slightly acidic aqueous solution is facile. The
Kochetkov method is also complicated by the difficulty
involved in removal of the ammonium carbonate.31 The
vigorus and prolonged (>3 days) lyophilization that is
needed to adaquately purify the samples leads to reduc-
tion in yields. In addition, a major side product, resulting
from a single molecule of ammonia glycosylating two
carbohydrate molecules (N,N-diglycosylamines), can be
seen in each of these methods.
The method we have described is a nonreductive
technique for efficiently derivatizing oligosaccharides
with allylamide groups at the glycosidic position. The
one-pot, two step reaction gives a stable, crude product,
readily purifiable. The product is obtained exclusivly in
the â-form. No carbohydrate protecting groups are
needed, although the hydroxyl groups become acylated
during the amine acylation step. Since the solvent/
reactant (allylamine) is volatile, simple evaporation
followed by the per-acetylation step gives a product that
is easy to purify by silica gel chromatography, in high
yield. The O-acetyl groups are also readily removed by
methoxide in high yield. The products are stable in air
in both the O-acetylated and-deacetylated form. This
method is perfectly suitable for sensitive carbohydrates
(e.g., fucosylated derivatives) and can be easily carried
out on very small scales (<5 mg) or large scales (>20 g).
No byproducts resulting from formation of N,N-diglyco-
sylamines or oxazolidines (in the case of 2-NAc carbohy-
drates, e.g., compounds 2, 5, and 6) were observed.
(24) Paulsen, H. Angew. Chem., Int. Ed. Engl. 1982, 21, 155.
(25) Schmidt, R. R. Angew. Chem., Int. Ed. Engl. 1986, 25, 212.
(26) Micheel, F.; Ko¨chling, H. Chem. Ber. 1957, 90, 1597.
(27) Hodge, J . E.; Moy, B. F. J . Org. Chem. 1963, 28, 2784.
(28) Likhosherstov, L. M.; Novikova, O. S.; Derevitskaja, V. A.;
Kochetkov, N. K. Carbohydr. Res. 1986, 146, C1.
(32) Dasgupta, F.; Rao, B. N. N. Exp. Opin. Invest. Drugs 1994, 3,
709.
(29) Isbell, H. S.; Frush, H. L. J . Org. Chem. 1958, 23, 1309.
(30) Lubineau, A.; Auge´, J .; Drouillat, B. Carbohydr. Res. 1995, 266,
211.
(33) Spevak, W.; Foxall, C.; Charych, D. H.; Dasgupta, F.; Nagy, J .
O. J . Med. Chem. 1996, 39, 1018.
(34) Osawa, T.; Nakazawa, Y. Biochim. Biophys. Acta 1966, 130,
56.
(31) Vetter, D.; Gallop, M. A. Bioconjugate Chem. 1995, 6, 316.

3420 J . Org. Chem., Vol. 61, No. 10, 1996
Spevak et al.
product on TLC than the peracetylated oligosaccharide. Upon
complete conversion of starting material into amino glycoside
product, the solvent was removed by evaporation and the crude
solid was treated with toluene and evaporated several times.
The flask was then chilled in an ice bath, and a solution of
60% pyridine, 40% acetic anhydride was added to give a
solution containing 500 mol % excess of acetic anhydride. The
reaction was protected from moisture, stirred, and allowed to
warm to ambient temperature overnight. The solvent was
removed by evaporation, and the residue was dissolved in
toluene and evaporated several times. The crude product was
purified by flash chromatography. Nearly all the purifed
peracetylated N-allylglycosylamides displayed multiplicity of
signals in the proton and carbon NMR spectra. This was
especially evident for the allyl, N-acetyl, and anomeric carbon
and proton signals. Heating these compounds to 85 °C in
DMSO-d6 showed peak coalessence.
Hz), 5.26 (dd, 1H, J ) 1.2, 3.5 Hz), 5.53 (br, 1H), 5.69 (m, 1H);
13C NMR (100 MHz, DMSO-d6, 25 °C) δ 20.22, 20.28 (2C),
20.38, 20.50, 21.72 (2C), 21.92, 60.79, 62.05, 67.04, 68.70
(0.5C), 68.90 (0.5C), 69.62, 70.23, 72.78, 72.97, 73.50 (0.5C),
73.68 (0.5C), 75.90, 79.10, 83.54, 99.91, 115.81 (0.5C), 116.42
(0.5C), 134.79 (0.5C), 135.52 (0.5C), 168.97, 169.22, 169.36,
169.43, 169.81 (0.5C), 169.82 (0.5C), 170.11, 170.18, 171.28;
13C NMR (100 MHz, DMSO-d6, 105 °C) δ 19.56, 19.61 (2C),
19.64, 19.73, 19.81, 19.84, 21.20, 60.55, 61.65, 66.95, 68.79,
68.95, 69.63, 70.12, 72.79, 73.65, 75.23, 99.37, 115.42, 134.76,
168.30, 168.45, 16863, 168.69, 169.13, 169.15, 169.35, 170.09;
mass spectrum (FAB+) 718 (MH+). Anal. Calcd for C31H43
-
NO18: C, 51.88; H, 6.04; N, 1.95. Found: C, 51.49; H, 6.03;
N, 1.87.
N-[(2-Acetam ido-3,4,6-tr i-O-acetyl-2-deoxy-â-D-glu copy-
r a n osyl)-(1f4)-O-(2-a ceta m id o-3,6-d i-O-a cetyl-2-d eoxy-â-
D-glu cop yr a n osyl)-(1f4)-2-a cet a m id o-3,6-d i-O-a cet yl-2-
N-(2,3,4,6-Tetr a -O-a cetyl-â-D-glu cop yr a n osyl)-3-a ceta -
m id o-1-p r op en e (1): amination reaction time, 72 h (neat
allylamine); chromatographed with ethyl acetate-hexane 1/2;
D-glu cop yr a n osyl]-3-a cet a m id o-1-p r op en e (5):
amination reaction time, 90 h (allylamine plus small amount
d eoxy-â-
of H2O); chromatographed with cloroform-methanol 20/1;
white solid (89%); mp 125 °C; [R]25 ) +2.3 (c ) l, CHCl3); 1H
white solid (84%); mp 280-282 °C dec; [R]25 ) -17.2 (c ) 2,
D
D
NMR (500 MHz, CDCl3) δ 1.95 (s, 3H), 1.97 (s, 3H), 2.00 (s,
3H), 2.02 (s, 3H), 2.04 (s, 3H), 3.73-3.82 (m, 2H), 3.85-3.93
(m, 1H),4.09 (dd, 1H, J ) 2.0, 12.4 Hz), 4.15 (dd, 1H, J ) 4.8,
12.2 Hz), 5.00 (t, 2H, J ) 9.6 Hz), 5.12 (bd 2H, J ) 16.0 Hz),
5.30 (t, 1H, J ) 9.7 Hz), 5.67-5.77 (m, 1H), 5.92 (d, 1H, J )
9.4 Hz); 13C NMR (500 MHz, CDCl3) δ 20.47 (3C), 20.59, 22.08,
46.38, 61.86, 68.28, 68.74, 73.25, 74.00, 80.12, 117.01, 134.76,
169.46, 169.81, 170.40 (2C), 172.31; HRMS FAB m/ z for
C19H28NO10 calcd 430.1705 (MH+), found 430.1713.
CHCl3/MeOH, 50/50); 1H NMR (500 MHz, CDCl3/CD3OD: 1/1,
ref CD3OD to 3.30 ppm) δ 1.82 (s, 3H), 1.87 (s, 3H), 1.96 (s,
3H), 1.97 (s, 3H), 1.98 (s, 3H), 1.99 (s, 3H), 2.00 (s, 3H), 2.03
(s, 3H), 2.04 (s, 3H), 2.06 (s, 3H), 2.11 (s, 3H), 3.57-3.75 (m,
7H), 3.79 (dd, 1H, J ) 6.7, 17.6 Hz), 3.89 (bd, 1H, J ) 13.3
Hz), 3.99 (dd, 1H, J ) 1.9, 12.5 Hz), 4.06 (m, 2H), 4.10 (t, 1H,
J ) 10.2 Hz), 4.35 (t, 1H, J ) 12.5 Hz), 4.36 (t, 1H, J ) 11.1
Hz), 4.46 (bd, 1H, J ) 11.5 Hz), 4.57 (m, 1H), 4.67 (d, 1H, J )
8.4 Hz), 4.95 (t, 1H, J ) 9.7 Hz), 5.10 (m, 4H), 5.25 (t, 1H, J
) 9.8 Hz), 5.66 (bd, 1H, J ) 9.8 Hz), 5.67-5.74 (m, 1H). 13C
NMR (100 MHz, CDCl3/CD3OD: 1/1, ref CD3OD to 49.00 ppm)
20.62 (2C), 20.69, 20.77, 20.88, 20.96 (2C), 22.30, 22.65, 22.85
(2C), 49.0 (2C buried under solvent), 51.60, 55.31, 55.59, 56.39,
62.47, 62.92, 63.40, 69.21, 72.15, 72.91, 73.24, 73.53, 74.36,
75.75, 76.52, 81.41, 101.14, 117.39, 135.45, 170.61, 171.22,
171.32 (2C), 171.35 (2C), 171.64, 171.80, 171.92, 172.59,
172.68; HRMS FAB m/ z for C43H63N4O23 calcd 1003.3883
(MH+), found 1003.3900.
N-(2-N-Acetyl-3,4,6-tr i-O-a cetyl-â-D-glu cop yr a n osyl)-3-
a ceta m id o-1-p r op en e (2): amination reaction time, 72 h
(neat allylamine); chromatographed with ethyl acetate; white
solid (60%); mp 132-134 °C; [R]25 ) -2.1 (c ) 1, CHCl3); 1H
D
NMR (200 MHz, CDCl3) δ 1.83 (s, 3H), 1.99 (s, 3H), 2.00 (s,
3H), 2.04 (s, 3H), 2.05 (s, 3H), 3.74 (m,1H), 3.88 (m, 2H), 4.13
(m, 2H), 4.25 (ddd, 1H, J ) 9.7, 9.7, 9.8 Hz), 5.08 (dd, 1H, J )
9.7, 9.7 Hz), 5.09 (m, 2H), 5.17 (dd, 1H, J ) 9.7, 9.7 Hz), 5.76
(m, 1H), 5.79 (d, 1H, J ) 9.7 Hz), 6.64 (d, 1H, J ) 9.8 Hz); 13
C
NMR (50 MHz, CDCl3) δ 20.54, 20.59, 20.64, 22.03, 22.98,
46.65, 51.24, 62.03, 68.26, 73.36, 74.29, 81.06, 117.11, 134.90,
169.30, 170.28, 170.51, 170.85, 172.80; mass spectrum (FAB+)
429 (MH+). Anal. Calcd for C19H28N2O9: C, 53.26; H, 6.59;
N, 6.54. Found: C, 52.93; H, 6.61; N, 6.39.
N-(2,3,4-Tr i-O-a cetyl-â-L-fu cop yr a n osyl)-3-a ceta m id o-
1-p r op en e (3): amination reaction time, 72 h (neat allyl-
amine); chromatographed with ethyl acetate-hexane 1/2;
viscous oil (98%); 1H NMR (200 MHz, CDCl3) δ 1.09 (d, 3H, J
) 6.4 Hz), 1.91 (s, 3H), 1.92 (s, 3H), 1.99 (s, 3H), 2.11 (s, 3H),
3.82 (m, 2H), 3.90 (m, 1H), 5.15 (m, 5H), 5.77 (m, 1H), 5.81 (d,
1H, J ) 9.0 Hz); 13C NMR (50 MHz, CDCl3) δ 16.07, 20.46,
20.52 (2C), 22.08, 46.54, 66.56 (0.5C), 66.81 (0.5C), 70.25, 71.03
(0.5C), 71.33 (0.5C), 71.64 (0.5C), 71.92 (0.5C), 80.29, 116.59
(0.5C), 116.72 (0.5C), 135.38, 169.71, 170.17, 170.24, 172.11;
HRMS FAB m/ z for C17H26NO8 calcd 372.1658 (MH+), found
372.1657.
N-[(2,3,4,6-Tetr a -O-a cetyl-r-D-ga la ctop yr a n osyl)(1f3)-
(2,4,6-t r i-O-a cet yl-â-D-ga la ct op yr a n osyl)-(1f4)-2-a cet a -
m id o-3,6-d i-O-a cet yl-2-d eoxy-â-D-glu cop yr a n osyl]-3-a c-
eta m id o-1-p r op en e (6): amination reaction time 96 h (neat
allylamine); chromatographed with chloroform-methanol 20/
1; white solid (93%); 1H NMR (500 MHz, CDCl3) δ 1.85 (s, 3H),
1.92 (s, 3H), 2.03 (s, 3H), 2.04 (s, 3H), 2.05 (s, 3H), 2.06 (s,
6H), 2.08 (s, 3H), 2.13 (s, 6H), 2.16 (s, 3H), 3.65-3.70 (m, 1H),
3.74 (t, 1H, J ) 9.3 Hz), 3.78 (t, 1H, J ) 7.0 Hz), 3.82 (dd, 2H,
J ) 2.9, 10.5 Hz), 3.84-3.91 (m, 2H), 4.00-4.20 (m, 7H), 4.44
(bt, 2H, J ) 8.0Hz), 5.06-5.20 (m, 5H), 5.21-5.26 (m, 1H),
5.31 (d, 1H, J ) 2.6 Hz), 5.43 (d, 1H, J ) 2.0 Hz), 5.67-5.84
(m, 1H), 5.72 (d, 1H, J ) 9.8 Hz), 5.85 (d, 1H, J ) 9.7 Hz);
HRMS FAB m/ z for C43
H61N2O25 calcd 1005.3570 (MH+),
found 1005.3563.
N-[(3-((Meth oxyca r bon yl)m eth yl)-2,4,6-tr i-O-a cetyl-â-
D-ga la ct op yr a n osyl)-(1f4)-O-[(2,3,4-t r i-O-a cet yl-r-L-fu -
copyr an osyl)-(1f3)]-O-2,6-di-O-acetyl-â-D-glu copyr an osyl]-
3-a ceta m id o-1-p r op en e (7): amination reaction time 72 h
(neat allylamine); treated crude product with methanol for
three hours at ambient temperature; chromatographed with
N-[4-O-â-(2,3,4,6-Tet r a -O-a cet yl-D-ga la ct op yr a n osyl)-
(2,3,6-t r i-O-a cet yl)-â-D-glu cop yr a n osyl]-3-a cet a m id o-1-
p r op en e (4): amination reaction time, 72 h (neat allylamine);
chromatographed with chloroform-methanol 200/1; white
solid (98%); mp 85-90 °C (scinters); [R]25 ) -2.0 (c ) 1,
chloroform-methanol 30/1; white solid (55%); mp 108-111 °C;
D
CHCl3); 1H NMR (400 MHz, DMSO-d6, 25 °C) δ 1.88 (s, 1.5H),
1.89 (s, 1.5H), 1.92 (s, 3H), 1.96(s, 3H), 1.99 (s, 3H), 2.00 (s,
3H), 2.04 (s, 3H), 2.07 (s, 3H), 2.09 (s, 3H), 3.65 (m, 0.5H),
3.81-3.91 (m, 2.5H), 3.95-4.01 (m, 4H), 4.22 (t, 1H, J ) 6.6
Hz), 4.34 (t, 1H, J ) 10.3 Hz), 4.77 (t, 1H, J ) 8.4 Hz), 4.85
(dd, 1H, J ) 8.0, 10.0 Hz), 4.91-5.00 (m, 2H), 5.04-5.11 (m,
1H), 5.16-5.23 (m, 2.5H), 5.29 (m, 0.5H), 5.45 (d, 0.5H, J )
8.9 Hz), 5.63-5.75 (m, 1H), 5.83 (d, 0.5H, J ) 8.9 Hz); 1H NMR
(400 MHz, DMSO-d6, 105 °C) δ 1.89 (s, 3H), 1.91 (s, 3H), 1.97
(s, 3H), 1.98 (s, 3H), 2.00 (s, 3H), 2.03 (s, 3H), 2.04 (s, 3H),
2.08 (s, 3H), 3.76 (m, 1H), 3.86 (app q, 2H, J ) 10.0, 18.2 Hz),
3.91 (m, 1H), 4.05 (m, 3H), 4.18 (dt, 1H, J ) 1.1, 6.4 Hz), 4.39
(dd, 1H, J ) 2.0, 12.0 Hz), 4.75 (d, 1H, J ) 7.9 Hz), 4.87 (dd,
1H, J ) 7.9, 16.2 Hz), 5.00 (app t, 2H), 5.10 (dd, 1H, J ) 1.5,
16.0 Hz), 5.14 (dd, 1H, J ) 3.6, 10.3 Hz), 5.23 (t, 1H, J ) 9.1
[R]25 ) -35.9 (c ) 3, CHCl3); H NMR (500 MHz, CDCl3) δ
1
D
1.06 (d, 3H, J ) 6.5 Hz), 1.89 (s, 3H), 1.91 (s, 3H), 1.94 (s,
3H), 1.95 (s, 3H), 2.00 (s, 3H), 2.02 (s, 3H), 2.07 (s, 3H), 2.09
(bs, 6H), 3.31 (dd, 1H, J ) 3.5, 9.4 Hz), 3.46 (bt, 1H, J ) 8.7
Hz), 3.58-3.72 (m, 4H), 3.72 (s, 3H), 3.80 (m, 2H), 4.04-4.07
(m, 1H), 4.11 (q, 2H, J ) 18.8 Hz), 4.21 (dd, 1H, J ) 8.5, 11.2
Hz), 4.30 (d, 1H, J ) 7.7 Hz),4.30-4.33 (m, 1H), 4.46 (q, 1H,
J ) 5.7 Hz), 4.65 (dd, 1H, J ) 1.7, 12.1 Hz), 4.92-4.96 (m,
3H), 5.06 (bd, 2H, J ) 16.4 Hz), 5.14 (bdd, 1H, J ) 3.1, 10.8
Hz), 5.27 (bd, 2H, J ) 19.7 Hz), 5.61-5.73 (m, 1H), 5.72 (d,
1H, J ) 9.2 Hz); 13C NMR (100 MHz, CDCl3) δ 15.70, 20.44,
20.56 (5C), 20.70 (3C), 21.94, 46.66, 52.33, 60.94, 63.85, 64.82,
66.06, 67.81, 68.15, 70.24, 70.62, 71.27, 72.05, 74.20, 74.75,
75.46, 80.05, 81.33, 95.39, 102.90, 116.75, 135.17, 169.56,
170.04, 170.33 (2C), 170.42, 170.50, 170.58, 170.72, 171.99,

Synthesis of N-Allylglycosylamides
J . Org. Chem., Vol. 61, No. 10, 1996 3421
172.26; HRMS FAB m/ z for C40H58NO24 calcd 936.3349 (MH+
- COCH2), found 936.3341.
173.64 (0.4C); mass spectrum (FAB+) 246 (MH+). Anal. Calcd
for C11H19NO5: C, 53.87; H, 7.81; N, 5.71. Found: C, 54.03;
H, 7.75; N, 5.64.
N-[(3-Su lfo-2,4,6-t r i-O-a cet yl-â-D-ga la ct op yr a n osyl)-
(1f4)-O-[(2,3,4-tr i-O-a cetyl-r-L-fu cop yr a n osyl)-(1f3)]-O-
2,6-d i-O-a cet yl-â-D-glu cop yr a n osyl]-3-a cet a m id o-1-p r o-
p en e (8): amination reaction time 72 h (neat allylamine);
chromatographed with chloroform-methanol 10/1; white solid
N-(4-O-â-D-Ga la ctop yr a n osyl-â-D-glu cop yr a n osyl)-3-a c-
eta m id o-1-p r op en e (12): recrystallized from MeOH/CH2Cl2
isolated as a white solid (79%); mp 195-196 °C; [R]25D ) +12.2
1
(c ) 1, H2O); H NMR (400 MHz, DMSO-d6, 25 °C) δ 1.99 (s,
(90%); mp 173-175 °C dec; [R]25 ) -44.3 (c ) 1.2, CH3OH);
1.17H), 2.07 (s, 1.83H), 3.42 (m, 5H), 3.72 (m, 1H), 3.89 (m,
2H), 4.08 (app. q, 1H, J ) 5.2, 10.5 Hz), 4.20 (m, 1H), 4.50
(m, 2H), 4.62 (t, 1H, J ) 4.5 Hz), 4.76 (m, 2H), 4.95 (d, 0.63H,
J ) 10.3 Hz), 5.10 (m, 2H), 5.25 (d, 0.37H, J ) 17.2 Hz), 5.32
(d, 0.63H, J ) 5.7 Hz), 5.40 (d, 0.37H, J ) 9.4 Hz), 5.75 (m,
0.63H), 5.87 (m, 0.37H); 1H NMR (400 MHz, DMSO-d6, 85 °C)
δ 2.06 (s, 3H), 3.35 (m, 2H), 3.48 (m, 1H), 3.58 (m, 2H), 3.68
(t, 1H, J ) 3.8 Hz), 3.75 (m, 1H), 3.86 (dd, 1H, J ) 4.9, 16.3
Hz), 3.99 (dd, 1H, J ) 5.4, 17.4 Hz), 4.15 (m, 2H), 4.26 (d, 1H,
J ) 7.4 Hz), 4.32 (t, 1H, J ) 5.3 Hz), 4.36 (d, 1H, J ) 5.4 Hz),
4.61 (s, 1H), 4.74 (d, 1H, J ) 4.1 Hz), 5.01 (br s, 1H), 5.17 (br
s, 1H), 5.84 (br s, 1H); 13C NMR (50 MHz, DMSO-d6, 25 °C) δ
21.94 (0.4C), 22.25 (0.6C), 42.84 (0.4C), 45.45 (0.6C), 60.45,
68.19, 69.78, 70.35 (0.4C), 70.58 (0.6C), 73.29, 75.59, 76.93,
77.12, 80.20, 81.41, 86.64, 103.81, 115.43 (0.4C), 116.33 (0.6C),
136.25, 170.76 (0.4C), 171.41 (0.6C); HRMS FAB m/ z for
C17H30NO11 calcd 424.1819 (MH+), found 424.1818. Anal.
Calcd for C17H29NO11: C, 48.22; H, 6.90; N, 3.31. Found: C,
47.56; H, 7.19; N, 3.36.
D
1H NMR (500 MHz, CD3OD) δ 0.98 (d, 3H, J ) 6.6 Hz), 1.71
(s, 3H), 173 (s, 3H), 1.77 (s, 3H), 1.79 (s, 3H), 1.85 (s, 1.5H),
1.86 (s, 1.5H), 1.86 (s, 3H), 1.87 (s, 3H), 1.92 (s, 3H), 1.94 (s,
3H), 3.50-3.58 (m, 1H), 3.63 (t, 1H, J ) 9.6 Hz), 3.73 (bd, 1H,
J ) 16.9 Hz), 3.82-3.88 (m, 1H), 3.93 (dt, 1H, J ) 5.2 Hz),
4.08 (dd, 1H, J ) 6.3, 11.7 Hz), 4.10-4.18 (m, 1H), 4.39 (bdd,
1H, J ) 10.0 Hz), 4.49 (dd, 2H, J ) 8.2, 15.3 Hz), 4.67-4.70
(m, 2H), 4.80-5.02 (m, 7H), 5.09 (dd, 2H, J ) 3.8, 12.9 Hz),
5.19 (bs, 1H), 5.44 (d, 1H, J ) 3.4 Hz), 5.44-5.61 (m, 1H); 13
C
NMR (100 MHz, CD3OD) δ 16.36, 20.43, 20.63, 20.75 (3C),
20.81, 20.91 (2C), 21.22, 22.30, (2C buried under solvent
signal), 62.86, 63.08, 65.53, 69.55, 69.67, 70.04, 71.22, 72.84
(2C), 75.54, 76.04, 76.62, 76.81, 96.89, 101.90, 117.46, 136.57,
171.46 (2C), 171.52, 171.99, 172.10, 172.32 (2C), 172.38,
174.69; HRMS FAB m/ z for C39H54NO26SNa2 calcd 1030.2440
(M+2Na+), found 1030.2450.
Gen er a l P r oced u r e for th e P r ep a r a tion of âNAc-a llyl
Glycosid es. The peracetylated â-NAc allyl glycoside is dis-
solved in anhydrous methanol to give a 0.1-0.01 M solution.
A catalytic amount (several drops) of 1 N NaOMe in MeOH
was added (pH ∼ 10), and the reaction was stirred at ambient
temperature for 3 h. J ust enough Dowex 50 resin (H+ form)
was added to neutralize the base, and then the solution was
filtered and evaporated to dryness. The products are usually
pure enough to require no further pruification; however they
can be recrystalized as in some cases below.
N-[(2-Aceta m id o-2-d eoxy-â-D-glu cop yr a n osyl)-(1f4)-O-
(2-a ceta m id o-2-d eoxy-â-D-glu cop yr a n osyl)-(1f4)-2-a ceta -
m id o-2-d eoxy-â-D-glu cop yr a n osyl]-3-a cet a m id o-1-p r o-
p en e (13): white solid (88%); mp 182-183 °C dec; [R]25
)
D
-6.2 (c ) 1, H2O); 1H NMR (500 MHz, CD3OD) δ 1.68 (s, 2H),
1.71 (s, 1H), 1.78 (s, 3H), 1.81 (s, 3H), 1.84 (s, 2H), 1.97 (bs,
1H), 3.09 (dt, 2H, J ) 1.7, 3.2, 4.8 Hz), 3.14 (dd, 0.6H, J ) 2.2,
6.5 Hz), 3.16 (dd, 0.4H, J ) 2.2, 6.5 Hz), 3.17 (m, 2H, J ) 2.0,
5.4, 7.4 Hz), 3.23 (dd, 1H, J ) 8.6, 10.3 Hz), 3.37-3.44 (m,
4H), 3.50 (dd, 2H, J ) 8.5, 10.3 Hz), 3.54-3.63 (m, 4H, J )
1.6, 10.0, 19.0 Hz), 3.69 (dd, 1H, J ) 2.1, 11.9 Hz), 3.70-3.93
(m, 3H), 4.29 (t, 2H, J ) 8.7 Hz), 4.81 (d, 0.6H, J ) 10.1 Hz),
4.97 (m, 1.8H, J ) 17.5 Hz), 5.40 (bs, 0.6H), 5.54-5.63 (m,
0.4H, J ) 4.7, 10.5, 16.9 Hz), 5.68-5.77 (m, 0.6H, J ) 4.6,
7.2, 10.5, 14.8 Hz); 13C NMR (100 MHz, CD3OD) δ 22.39, 22.73,
23.01, 23.07, 53.55, 54.22, 56.64, 57.38, 61.65, 61.80, 62.58,
72.00, 74.09, 74.65, 74.78, 75.74, 76.52, 78.15, 79.04, 80.83,
81.54, 103.01, 103.21, 116.68 (0.2C), 117.22 (0.8C), 137.16,
173.53, 173.70, 173.81, 175.01; HRMS FAB m/ z for C29H49N4O16
calcd 709.3144 (MH+), found 709.3147.
N-(â-D-glu cop yr a n osyl)-3-a ceta m id o-1-p r op en e (9): iso-
lated as a white solid (98%); mp 137-139 °C; [R]25 ) -4.2 (c
D
) 1, H2O); 1H NMR (500 MHz, CD3OD) δ 1.95 (s, 1H), 2.03 (s,
2H), 3.09 (q, 1H, J ) 9.4 Hz), 3.16-3.29 (m, 2.4H), 3.33 (t,
0.6H, J ) 8.8 Hz), 3.46 (dq, 1H, J ) 2.8, 5.3,6.0 Hz), 3.66 (dt,
1H, J ) 2.0, 12.9 Hz), 3.81 (dd, 1H, J ) 5.1,15.3 Hz), 3.88 (dd,
1H, J ) 6.1, 16.6 Hz), 4.67 (d, 0.6H, J ) 8.9 Hz), 4.87 (dd,
0.4H, J ) 1.2, 10.3 Hz), 5.02 (m, 1H, J ) 1.4, 11.9, 17.3 Hz),
5.13 (d, 0.4H, J ) 17.3 Hz), 5.37 (dd, 0.6H, J ) 8.9 Hz), 5.65-
5.73 (m, 0.6H, J ) 0.8, 5.9, 10.5 Hz), 5.73-5.84 (m, 0.4H, J )
5.5, 10.7 Hz); 13C NMR (100 MHz, CD3OD) δ 22.07 (0.6C),
22.49 (0.4C), 44.86 (0.4C), 47.35 (0.6C), 62.79, 71.17 (0.6C),
71.26 (0.4C), 71.94, 79.07 (0.4C), 80.17 (0.6C), 83.71, 88.78,
116.55 (0.6C), 117.27 (0.4C), 136.44 (0.6C), 136.58 (0.4C),
174.35 (0.6C), 175.39 (0.4C); HRMS FAB m/ z for C11H20NO6
calcd 262.1291 (MH+), found 262.1288. Anal. Calcd for
C11H19NO6: C, 50.57; H, 7.33; N, 5.36. Found: C, 50.52; H,
7.52; N, 5.34.
N-[(r-D-galactopyr an osyl)-(1f3)-(â-D-galactopyr an osyl)-
(1f4)-2-a ceta m id o-2-d eoxy-â-D-glu cop yr a n osyl]-3-a ceta -
m id o-1-p r op en e (14): white solid (96%); 1H NMR (500 MHz,
CD3OD) δ 1.73 (s, 2H), 1.76 (s, 1H), 1.83 (s, 1H), 1.88 (s, 2H),
3.34 (bdd, 1H, J ) 6.2, 10.8 Hz), 3.42 (dd, 1H, J ) 4.6, 6.9
Hz), 3.46 (d, 1H, J ) 9.8 Hz), 3.50 (bs, 2H), 3.52-3.56(m, 4H),
3.60 (m, 2H, J ) 7.6, 9.2, 11.5 Hz), 3.67 (bs, 3H), 3.67 (bd, 1H,
J ) 4.2 Hz), 3.72 (bs, 1H), 3.74 (d, 2H, J ) 0.8Hz), 3.87 (bs,
1H), 4.04 (bt, 1H, J ) 6.0 Hz), 4.27 (bd, 1H, J ) 5.8 Hz), 4.86
(bs, 1H), 4.91-5.05 (m, 2.6H, J ) 9.9, 10.6, 18.0 Hz), 5.47 (bs,
0.4H), 5.61-5.66 (m, 0.4H, J ) 5.5, 6.4 Hz), 5.67-5.78 (m,
0.6H, J ) 2.6, 3.5, 4.5, 6.7 Hz); 13C NMR (100 MHz, CD3OD)
δ 22.63, 22.71, 53.58, 62.21, 62.46, 62.79, 66.69, 70.19, 71.05,
71.18, 71.39, 72.30, 74.70, 76.72, 79.15, 80.01, 80.25, 81.12,
97.79, 105.15, 107.09, 116.69(0.2C), 117.20 (0.8C), 137.17,
174.10, 175.05; HRMS FAB m/ z for C25H43N2O16 calcd 627.2613
(MH+), found 627.2615.
N-(2-N-Acetyl-â-D-glu cop yr a n osyl)-3-a ceta m id o-1-p r o-
p en e (10): isolated as a white solid (99%); mp 96-98 °C
(scinters); [R]25 ) +17.3 (c ) 1, H2O); 1H NMR (200 MHz,
D
CD3OD) δ 1.94 (s, 1.83H), 1.98 (s, 1.17H), 2.09 (s, 1.83H), 2.24
(s, 1.17H), 3.38 (m, 2H), 3.61 (m, 1H), 3.83 (m, 1H), 3.91 (m,
1H), 3.95 (m, 1H), 5.16 (m, 4H), 5.66 (d, 1H, J ) 9.7 Hz), 5.91
(m, 1H), 7.97 (d, 0.61H, J ) 9.5 Hz), 8.07 (d, 0.39H, J ) 8.8
Hz); 13C NMR (50 MHz, CD3OD) δ 22.41, 22.81 (0.5C), 22.91
(0.5C), 48.01, 54.01 (0.5C), 54.89 (0.5C), 62.89, 71.83, 76.36,
80.48, 82.60 (0.5C), 87.30 (0.5C), 116.66 (0.5C), 117.24 (0.5C),
136.14 (0.5C), 137.13 (0.5C), 173.54 (0.5C), 173.62 (0.5C),
174.13 (0.5C), 174.91 (0.5C); HRMS FAB m/ z for C13H23N2O6
calcd 303.1556 (MH+), found 303.1551.
N-[O-(3-O-((Met h oxyca r b on yl)m et h yl)-â-D-ga la ct op y-
r a n osyl)-(1f4)-O-[(r-L-fu cop yr a n osyl)-(1f3)]-O-(â-D-glu -
copyr an osyl]-3-acetam ido-1-pr open e (15): purified by silica
gel column chromatography eluting with 3:2:1 ethyl acetate:
N-(â-L-F u cop yr a n osyl)-3 a ceta m id o-1-p r op en e (11): re-
crystallized from ethylacetate isolated as a white solid (60%);
mp 133-134 °C; 1H NMR (200 MHz, CDCl3/CD3OD) δ 1.14 (t,
3H, J ) 6.1 Hz), 1.99 (s, 1.68H), 2.06 (s, 1.32H), 3.54 (m, 4H),
3.70 (m, 1H), 4.21 (d, 0.17H, J ) 4.2 Hz), 4.35 (d, 0.1H, J )
4.3 Hz), 4.54 (d, 0.53H, J ) 8.7 Hz), 4.67 (d, 0.2H, J ) 4.9
Hz), 5.04 (m, 2.4H), 5.32 (d, 0.6H, J ) 8.6 Hz), 5.76 (m, 1H);
13C NMR (50 MHz, CDCl3/CD3OD) δ 16.03, 21.52 (0.6C), 21.83
(0.4 C), 43.78 (0.6C), 46.01 (0.4C), 67.68, 71.11 (0.6C), 71.38
(0.4C), 72.53, 74.48 (0.6C), 74.68 (0.4C), 82.31 (0.6C), 87.71
(0.4C), 115.85 (0.6C), 116.39 (0.4C), 134.72, 172.18 (0.6C),
2-propanol:H2O; white solid (76%); mp 190 °C dec; [R]25
)
D
-43.9 (c ) 1.5, H2O); 1H NMR (200 MHz, D2O) δ 1.02 (d, 3H,
J ) 6.4 Hz), 2.02 (s, 1.3H), 2.08 (s, 1.7H), 3.29 (app dd, 1H, J
) 2.6, 9.8 Hz), 3.41 (t, 3H, J ) 7.1 Hz), 3.52-3.84 (m, 14H),
3.89 (s, 3H), 4.31 (d, 1H, J ) 7.3 Hz), 4.64 (m, 2H, obscured by
HOD signal), 5.04 (m, 2.5H), 5.26 (d, 1H, J ) 3.7 Hz), 5.36 (d,
0.5H, J ) 8.2 Hz), 5.62-5.76 (m 1H); 13C NMR (100 MHz, D2O)
δ 16.25, 22.18 (0.4C), 22.68 (0.6C), 44.78 (0.4C), 47.50 (0.6C),
60.58, 62.64, 66.08, 67.53, 69.01 (0.4C), 69.21 (0.6C), 70.23,

3422 J . Org. Chem., Vol. 61, No. 10, 1996
Spevak et al.
71.00, 72.00, 72.47 (0.4C), 72.94 (0.6C), 73.16, 75.81, 78.23,
78.42, 78.70, 79.01, 82.75, 83.54, 88.04, 99.39 (0.4C), 102.66
(0.6C), 117.56 (0.6C), 118.30 (0.4C), 134.78 (0.4C), 134.89
(0.6C), 176.18 (0.4C), 177.63 (0.6C), 179.43; HRMS FAB m/ z
for C26H43NO17 calcd 664.2427 (M + Na+), found 664.2429.
N-[(3-Su lfo-â-D-gla ctop yr a n osyl)-(1f4)-O-[(r-L-fu cop y-
r an osyl)-(1f3)]-O-â-D-glu copyr an osyl]-3-acetam ido-1-pr o-
61.43, 62.79, 67.53, 68.36, 70.35, 71.19, 72.98, 73.36, 73.74,
74.48, 76.36, 79.58, 80.42, 82.04, 84.09, 88.92, 100.37 (0.6C),
103.62 (0.4C), 116.62 (0.6C), 117.27 (0.4C), 136.44 (0.6C),
136.62 (0.4C), 174.38 (0.6C), 175.52 (0.4C); HRMS FAB m/ z
for C23H39NO18SNa calcd 672.1786 (MH+), found 672.1792.
Ack n ow led gm en t. This research was supported by
the Director, Office of Energy Research, Office of Basic
Energy Sciences, Division of Material Sciences, the
Division of Energy Biosciences of the U.S. Department
of Energy, and Glycomed, Inc.
p en e (16): yellow solid (71%); mp 200 °C dec; [R]25 ) -40.3
D
(c ) 1.5, H2O); 1H NMR (500 MHz, CD3OD) δ 0.93 (d, 3H, J )
6.6 Hz), 1.88 (s, 1.1H), 1.96 (s, 1.9H), 3.21-3.33 (m, 2H), 3.40-
3.47 (m, 2H, J ) 4.8, 5.8, 6.4, 9.5 Hz), 3.49 (bs, 2H), 3.54 (m,
3H, J ) 3.5, 4.0 Hz), 3.60 (bt, 1H, J ) 9.5 Hz), 3.58-3.65 (m,
1H), 3.69 (bdt, 2H, J ) 2.8, 9.7 Hz), 3.77 (dd, 1H, J ) 5.5, 14.4
Hz), 3.77-3.83 (m, 1H), 3.96 (bdd, 2H, J ) 2.2, 14.0 Hz), 4.28
(dd, 1H, J ) 3.2, 7.6 Hz), 4.56 (q, 1H, J ) 6.6 Hz), 4.80 (d, 1H,
J ) 9.9 Hz), 4.96 (m, 1H, J ) 16.6 Hz), 5.05 (d, 0.6H, J ) 17.2
Hz), 5.16 (d, 0.4H, J ) 3.9 Hz), 5.17 (d, 0.6H, J ) 3.8 Hz),
5.27 (d, 0.4H, J ) 9.0 Hz), 5.59-5.66 (m, 0.6H, J ) 4.9, 5.6,
6.3 Hz), 5.66-5.74 (m, 0.4H, J ) 4.8, 5.3, 6.4 Hz); 13C NMR
(100 MHz, D2O) δ 16.59, 22.11 (0.5C), 22.53 (0.5C), 47.61,
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra for
compounds 1, 3, 5, 7, 8, 10, 13, 15, and 16 (9 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
J O9522522