Asymmetric Strecker Synthesis of C-Glycopeptide

Full text of DOI:10.1021/jo000034p

4440
J . Org. Chem. 2000, 65, 4440-4443
Sch em e 1
Asym m etr ic Str eck er Syn th esis of
C-Glycop ep tid e
Ste´phane P. Vincent, Axel Schleyer, and
Chi-Huey Wong*
Department of Chemistry, BCC 338, The Scripps Research
Institute, 10550 North Torrey Pines Road,
La J olla, California 92037
Received J anuary 11, 2000
Glycopeptides serve not only as key components in
cellular recognition processes but also as modulators of
protein function.1,2 Small glycopeptides have also become
attractive therapeutic targets as exemplified by the
recent preparation of a glycopeptide-based vaccine that
is now in clinical trials against prostate cancer.3 Neverthe-
less, the use of glycopeptides as pharmaceuticals is
limited by their chemical and enzymatic instability in
vivo. This drawback can be overcome by the use of
C-glycosides.4
Several procedures have been reported for the asym-
metric synthesis of C-linked serine5 and asparagine6
glycoconjugates. The strategies developed include the
coupling of an activated chiral amino acid analogue,7-9
the use of asymmetric reactions such as catalytic hydro-
genation,10 the Wittig rearrangement,11 or the chiral
auxiliary based enolate methodology.12 In the course of
developing new sialyl Lewis x mimics,13-15 we were
interested in the synthesis of glycopeptide analogues with
the amino acid function closer to the sugar moiety. To
date, however, only a few are available to provide such
structures that involve either a Sharpless asymmetric
dihydroxylation of allyl glycosides or a free-radical ad-
dition of bromo glycosides to dehydroalanine deriva-
tives.16,17 Here, we report our investigation on the Streck-
er reaction as a general stereoselective method for
C-glycopeptide synthesis.
Our strategy relies on the coupling of a fully benzylated
C-glycoside18,19 with a benzylic amine in the presence of
acetone cyanohydrin as a cyanide donor (Scheme 1). The
starting aldehydes, obtained in three steps following
known procedures,20,21 have already been used in numer-
ous synthetic procedures.12,22-28 To our surprise, the sugar
did not induce any chirality (see Table 1, entries 6 and
10) in the mannose and the galactose series, although
1-amino sugars have previously been successfully em-
ployed as chiral auxiliaries.29,30 Thus, we turned our
attention to the use of (S)-R-methylbenzylamine, which
has been described as one of the best chiral auxiliaries
for the Strecker synthesis and always gives the expected
(S)-configurated amino acid.31-33 The intermediate imine
is first formed at room temperature with magnesium
sulfate or molecular sieves as a desiccant and then
allowed to react with acetone cyanohydrin. The diaste-
reoisomeric excess of each reaction was determined by
NMR. As expected, in any solvent the selectivity was
always enhanced by lowering the reaction temperature.
We were able to separate the resulting R-aminonitrile
mixture by standard silica gel chromatography only in
the fucose and glucose series. However, in each case, pure
(1) For a recent review, see: Marcaurelle, L.; Bertozzi, C. R. Chem.
Eur. J . 1999, 5, 1384-1390.
(2) Kihlberg, J .; Elofsson, M. Curr. Med. Chem. 1997, 4, 85-116.
(3) Kuduk, S. D.; Schwarz, a. B.; Chen, X.-T.; Glunz, P. W.; Sames,
D.; Ragupathi, G.; Livingston, P. O.; Danishefsky, S. J . J . Am. Chem.
Soc. 1998, 120, 12474-12485.
(18) Kishi, Y. Pure Appl. Chem. 1989, 61, 313-324.
(19) Lewis, M. D.; Cha, J . K.; Kishi, Y. J . Am. Chem. Soc. 1982,
104, 4976-4978.
(4) Postema, M. H. D. Tetrahedron 1992, 48, 8545-8599.
(5) Herpin, T.; Motherwell, W.; Weibel, J .-M. Chem. Commun. 1997,
923.
(20) Woltering, T. J .; Weitz-Schmidt, G.; Wong, C.-H. Tetrahedron
Lett. 1996, 37, 9033-9036.
(21) Uchiyama, T.; Woltering, T. J .; Wong, W.; Lin, C.-C.; Kajimoto,
T.; Takebayashi, M.; Weitz-Scmidt, G.; Asakura, T.; Noda, M.; Wong,
C.-H. Bioorg. Med. Chem. 1996, 4, 1149-1165.
(22) Marron, T. G.; Woltering, T. J .; Weitz-Scmidt, G.; Wong, C.-H.
Tetrahedron Lett. 1996, 37, 9037-9040.
(6) Burkhart, F.; Hoffman, M.; Kesler, H. Angew. Chem., Int. Ed.
Engl. 1997, 36, 1191-1192.
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1992, 57, 6092-6094.
(8) Urban, D.; Skrydstrup, T.; Beau, J .-M. Chem. Commun. 1998,
955-956.
(23) Tsai, C.-Y.; Park, W.; Weitz-Schmidt, G.; Wong, C.-H. Bioorg.
Med. Chem. Lett. 1998, 8, 2333-2338.
(9) Pearce, A. J .; Ramaya, S.; Thorn, S. N.; Bloomberg, G. B.; Walter,
D. S.; Gallager, T. J . Org. Chem. 1999, 64, 5453-5462.
(10) Debenham, S. D.; Debenham, J . S.; Burk, M. J .; Toone, E. J . J .
Am. Chem. Soc. 1997, 119, 9897-9898.
(24) J acques, F.; Dupeyroux, H.; J oly, J .-P.; Chapleur, Y. Tetrahe-
dron Lett. 1997, 38, 73-76.
(25) Arya, P.; Ben, R. N.; Qin, H. Tetrahedron Lett. 1998, 39, 6131-
6134.
(11) Lay, L.; Meldal, M.; Nicotra, F.; Panza, L.; Russo, G. Chem.
Commun. 1997, 1469-1470.
(26) Bertozzi, C. R.; Bednarski, M. D. J . Org. Chem. 1991, 56, 4326-
4329.
(12) Ben, R. N.; Orellana, A.; Arya, P. J . Org. Chem. 1998, 63, 4817-
(27) Panek, J . S.; Sparks, M. A. J . Org. Chem. 1989, 54, 2034-2038.
(28) Sutherlin, D. P.; Spark, T. M.; Hugues, R.; Armstrong, R. W.
J . Org. Chem. 1996, 61, 8350-8354.
4820.
(13) Wong, C.-H.; Moris-Varas, F.; Lin, C.-C.; Gong, K. W.; Weitz-
Schmidt, G. J . Am. Chem. Soc. 1997, 119, 8152-8158.
(14) Lampe, T. F. J .; Weitz-Schmidt, G.; Wong, C.-H. Angew. Chem.,
Int. Ed. Engl. 1998, 97, 1707-1711.
(29) Kunz, H.; Sager, W.; Schanzenbach, D.; Decker, M. Liebigs Ann.
Chem. 1991, 649-54.
(30) Kunz, H.; Sager, W.; Pfrengle, W.; Laschat, S.; Schanzenbach,
D. Chem. Pept. Proteins 1993, 5/ 6, 91-8.
(15) Simanek, E. E.; McGarvey, G. J .; J ablonowski, J . A.; Wong, C.-
H. Chem. Rev. 1998, 98, 833-862.
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(32) Stout, D. M.; Black, L. A.; Matier, W. L. J . Org. Chem. 1983,
48, 5369-5373.
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6601-6604.
(17) Kessler, H.; Wittman, V.; Kock, M.; Kottenhahn, M. Angew.
Chem., Int. Ed. Engl. 1992, 31, 902-904.
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1279.
10.1021/jo000034p CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/06/2000

Notes
J . Org. Chem., Vol. 65, No. 14, 2000 4441
Ta ble 1
entry
substrate
solvent
desiccant
compd
T (°C)
amine
R/Sa
yield (%)
79
73
82
67
69
85
89
1
2
3
4
5
6
7
8
9
10
11
12
13
fucose
fucose
THF
CH2Cl2
THF
CH2Cl2
CH2Cl2
THF
MgSO4
MgSO4
MgSO4
MS 4 Å
MgSO4
MS 4 Å
MgSO4
MS 4 Å
MgSO4
MgSO4
MgSO4
MS 4 Å
MgSO4
5
5
6
6
6
6
2
2
2
7
7
7
7
-20
-85
-20
-70
-15
-20
-20
-70
-70
-20
-40
-70
-20
1
1
1
1
1/5.2
1/1.3
1/3.5
2.1/1
7/1
1/1
1/1.8
2/1
4.1/1
1/1
ND
3/1
1/1.1
galactose
galactose
galactose
galactose
glucose
glucose
glucose
mannose
mannose
mannose
mannose
1
BnNH2
THF
1
1
1
CH2Cl2
CH2Cl2
THF
THF
CH2Cl2
THF
81
80
78
BnNH2
1
1
1
no reaction
75
84
a
Determined by 1H NMR.
Sch em e 2
Sch em e 3
diastereoisomers could be obtained as methyl esters after
methanolysis of the nitrile function. The absolute ster-
eochemistry of the formed stereocenter was determined
by 1H NMR according to the well-established rules
described by Stout et al.32-34 We further confirmed the
stereochemistry by converting 3 to the known C-gluco-
L-alanine analogue 4 (Scheme 2).17 Therefore, asymmetric
Strecker reactions, employing 1 as chiral inducer and
C-glycosylacetaldehydes, give in THF the expected
aminonitrile with the (S) configuration.
Solven t Effect. To improve the selectivity, we tried
several other conditions and found that when performing
the reaction in CH2Cl2, the diastereoselectivities were
reversed as exemplified in entries 3, 5, 7, 9, 12, and 13.
In the mannose, glucose, and galactose series, the reac-
tions gave opposite stereoselectivities when carried out
in CH2Cl2 vs THF. Table 1 collects representative data
taken from experiments for which the best diastereose-
lectivities have been obtained as well as experiments
showing the characteristics of the reaction. In CH2Cl2,
the temperature can be significantly lowered (entries 11
and 12) to improve the selectivity. In both solvents, we
obtained good stereoselectivities, especially in the reac-
tion of the fucosyl and the galactosyl imines. It is,
however, unclear why the mannose derivatives gave
poorer selectivities considering that neither the mannosyl
nor the galactosyl moieties induce any stereoselectivities
with benzylamine (entries 6 and 10). Furthermore, we
found that the use of magnesium sulfate in place of
molecular sieves increased the stereoselectivities in the
glucose and galactose series (entries 4, 5, 8, and 9).
cyanide.32,33 So far, this selectivity had only been de-
scribed for the Strecker reaction involving 1 as chiral
inducer. Surprisingly, in CH2Cl2, the 1,3-trans-selectivity
was observed, corresponding to a Cram-type stereoin-
duction.37 In the fucose series, even if the Cram product
ratio is increased from CH2Cl2 to THF, the Felkin-Anh
product, with the S configuration, is still predominantly
formed (Table 1, entry 2). It is still unclear why the
Strecker reaction proceeds through different transition
states from a solvent to another but this phenomenon
seems to be quite general.
Ap p lica tion to th e Syn th esis of F u cop ep tid es
Mim etics. One application of this methodology is il-
lustrated in Scheme 4, where the amino nitrile 7 result-
ing from the asymmetric Strecker reaction was trans-
formed into the methyl ester. Saponification then gives
the C-fucopeptide 8, which could be hydrogenolysed to
the fully deprotected analogue 9. This C-fucosyl alanine
derivative can be further functionalyzed and used as core
structure to generate libraries of biologically relevant
fucopeptide mimetics.
Ra tion a liza tion of th e Ster eoselectivity. The 1,3-
syn-stereoselectivity was obtained when the Strecker
reaction was performed in THF, corresponding to a
Felkin-Ahn model (see Scheme 3).35 This Felkin-Ahn
selectivity had previously been observed in water-
alcoholic mixtures containing sodium36 or potassium
In conclusion, we developed a new stereoselective way
to synthesize glycoalanine derivatives using the Strecker
reaction. An interesting solvent-dependent reversal of
(36) Speelman, J . C.; Talma, A. G.; Kellogg, R. M.; Meetsma, A.;
Boer, J . L. d.; Beurskens, P. T.; Bosman, W. P. J . Org. Chem. 1989,
54, 1055-1062.
(37) This type of solvent dependent reversal of induction has a few
precedents in the literature. For references, see: Kunz, H.; Sager, W.;
Pflenle, W.; Schanzenbach, D. Tetrahedron Lett. 1988, 29, 4397-4400.
(34) In all cases, in THF with (S)-(-)-R-methylbenzylamine 1, the
protons vicinal to the nitrile of the major isomer were always upfield,
compared to the minor isomer, in the NMR spectra. The (S) stereo-
chemistry was therefore assigned to the major isomer.
(35) Bloch, R. Chem. Rev. 1998, 98, 1407-1438.

4442 J . Org. Chem., Vol. 65, No. 14, 2000
Notes
Sch em e 4
1.65 (d, J ) 6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 169.52,
139.69, 139.34, 139.14, 138.93, 136.81, 130-128, 81.44, 79.57,
78.38, 75.71, 75.25, 74.24, 74.02, 72.96, 72.32, 69.73, 59.55, 30.88,
20.67; HRMS (MaldiFTMS) calcd for C45H49N1O7 716.3587,
found 716.3606.
stereoinduction was observed from THF to CH2Cl2,
allowing the preparation of both epimers using the same
chiral inducer (S)-methylbenzylamine.
Exp er im en ta l Section
2(S)-[(1(S)-P h en yleth yl)a m in o]-3-[2,3,4,6-tetr a ben zyl-r-
L-fu cop yr a n osyl]p r op a n en itr ile (5). The general procedure
was used for the synthesis (66% yield in pure (S) isomer): 1H
NMR (600 MHz, CDCl3) δ 7.45-7.16 (m, 20H), 4.74 (m, 2H),
4.63 (m, 3H), 4.48 (d, J ) 11.8 Hz, 1H), 4.38 (td, J ) 7.3 Hz J )
3.2 Hz, 1H), 4.04 (q, J ) 6.6 Hz, 1H), 3.82 (dd, J ) 7.1, 3.0 Hz,
1H), 3.79 (m, 1H), 3.71 (t, J ) 3.0 Hz, 1H), 3.69 (dd, J ) 7.1, 2.8
Hz, 1H), 3.33 (dd, J ) 8.7, 3.3 Hz, 1H), 2.11 (ddd, J ) 14.7, 11.1,
3.3 Hz, 1H), 1.75 (ddd, J ) 14.7, 8.9, 2.0 Hz, 1H), 1.72 (bs, 1H),
1.32 (d, J ) 6.6 Hz, 3H), 1.19 (d, J ) 6.5 Hz, 3H); 13C NMR (150
MHz, CDCl3) δ 143.02, 138.47, 138.67, 138.5, 137.76, 136.50,
129.63, 128-127, 125.85, 120.28, 73.27, 75.80, 73.32, 73.17,
73.14, 73.04, 68.86, 63.03, 56.37, 45.81, 25.14, 15.36; HRMS (M
+ Cs+) calcd for C38H42N2O4 723.2199, found 723.2221.
2-[(1(S)-P h en ylet h yl)a m in o]-3-[2,3,4,6-t et r a b en zyl-R-D-
ga la ctop yr a n osyl]p r op a n en itr ile (6). The general procedure
was used for the synthesis. This compound was isolated as a
diastereoisomeric mixture (82% yield): 1H NMR (600 MHz,
CDCl3) δ 7.35-7.05 (m, 25H), 4.75-4.45 (m, 8H), 4.20 (td, J )
10.3, 4.0 Hz, 1H), 4.01 (q, J ) 6.6 Hz, 1H), 3.94 (m, 1H), 3.90
(m, 1H), 3.71 (m, 1H), 3.65 (dd, J ) 7.0, 2.6 Hz, 1H), 3.59 (dd, J
) 10.6, 5.1 Hz, 1H), 3.26 (dd, J ) 8.4, 5.9 Hz, 1H), 2.08 (ddd, J
) 14.0, 10.2, 5.9 Hz, 1H), 1.87 (ddd, J ) 14.0 Hz, 1H), 1.72 (bs,
1H), 1.29 (d, J ) 6.6 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ
143.44, 138.43, 138.41, 138.39, 138.33, 138.31, 137.90, 128-125,
120.28, 76.48, 76.13, 74.03, 73.33, 73.27, 73.24, 73.18, 73.02,
72.99, 72.52, 67.31 (S), 66.28 (R), 56.58 (S), 56.05 (R), 45.83 (S),
45.54 (R), 31.88, 24.68; HRMS (M + Cs+) calcd for C45H48N2O5
829.2618, found 829.2648.
Gen er a l P r oced u r es. Str eck er Rea ction . To an aldehyde
(prepared by standard procedure) in the appropriate solvent (see
Table 1, c ) 0.2 M) was added the desiccant and (S)-phenyl-
ethylamine (2.0 equiv) at room temperature. The reaction
mixture was then cooled to the temperature indicated in Table
1, and acetone cyanohydrin (5.0 equiv) was injected. After the
reaction was complete, the mixture was poured onto ice-water,
saturated with sodium bicarbonate, and extracted with ethyl
acetate. The combined organic layers were dried over magnesium
sulfate and the solvent removed in vacuo. The product was
purified by column chromatography on silica gel.
Am in on it r ile Con ver sion t o t h e Cor r esp on d in g r-
Am in o Meth yl Ester . Dry methanol was added to aminonitriles
(c ) 0.1 M). The solution was saturated with HCl gas at 0 °C
and kept at this temperature for an additional 2 h. The reaction
mixture was then poured on ice-water and neutralized with
sodium hydroxide and sodium bicarbonate until pH 7.5. After
extraction, the combined organic layers were dried over mag-
nesium sulfate and the solvent removed in vacuo. The residual
mixture was purified by column chromatography on silica gel.
Con ver sion of th e Meth yl Ester to th e Cor r esp on d in g
Acid . The methyl ester was dissolved in a 10:1 methanol/water
mixture. Lithium hydroxide was added (apparent pH ) 9.5-
10.5), the mixture was stirred at room temperature for 16 h,
the solution was reacidified to pH 1, and the aqueous layer was
extracted three times with ethyl acetate. The combined organic
fractions were dried with magnesium sulfate, and the solvent
was removed in vacuo.
2-[(1(S)-P h en ylet h yl)a m in o]-3-[2,3,4,6-t et r a b en zyl-r-D-
m a n n op yr a n osyl]p r op a n en itr ile (7). The general procedure
was used for the synthesis. This compound was isolated as a
diastereoisomeric mixture (84% yield): 1H NMR (400 MHz,
CDCl3) (R) diastereoisomer δ 7.31-7.14 (m, 25H), 4.85-4.42 (m,
8H), 4.34 (ddd, J ) 10.3 Hz J ) 7.3 Hz J ) 3.5 Hz, 1H), 3.97 (q,
J ) 6.5 Hz, 1H), 3.91 (bt, J ) 4.3 Hz, 1H), 3.79-3.61 (m, 5H),
3.51 (m, 1H), 1.95 (m, 2H), 1.58 (bs, 1H), 1.26 (d, J ) 6.5 Hz,
3H); (S) diastereoisomer δ 7.31-7.14 (m, 25H), 4.85-4.42 (m,
8H), 4.17 (bq, J ) 7.0 Hz, 1H), 4.05 (q, J ) 6.2 Hz, 1H), 3.79-
3.61 (m, 5H), 3.51 (m, 1H), 3.43 (bt, J ) 7.6 Hz, 1H), 1.95 (m,
2H), 1.58 (bs, 1H), 1.33 (d, J ) 6.2 Hz, 3H).
2(S)-[(1(S)-P h en yleth yl)a m in o]-3-[2,3,4,6-tetr a ben zyl-r-
L-fu cop yr a n osyl]p r op a n oic Acid (8). The general procedure
was used for the synthesis (95% yield): 1H NMR (600 MHz, CD3-
OD) δ 7.37-7.10 (m, 20H), 4.88 (bs, 2H), 4.65 (m, 2H), 4.48 (m,
3H), 4.21 (td, J ) 10.1, 3.9 Hz, 1H), 3.85 (m, 1H), 3.82 (dd, J )
6.2, 2.9 Hz, 1H), 3.74 (bt, J ) 3.8 Hz, 1H), 3.71 (dd, J ) 6.2, 3.8
Hz, 1H), 3.46 (bd, J ) 5.4 Hz, 1H), 2.29 (m, 1H), 2.00 (m, 1H),
1.64 (d, J ) 6.8 Hz, 3H), 1.11 (d, J ) 6.6 Hz, 3H); 13C NMR (150
MHz, CD3OD) δ 177.62, 139.37, 139.28, 138.90, 136.93, 130.10,
130.01, 128.9-128.1, 77.33, 76.37, 75.39, 73.43, 73.41, 73.32,
73.22, 70.21, 67.25, 58.64, 29.99, 19.39, 14.65; HRMS (M + Cs+)
calcd for C39H45NO6 756.2301, found 756.2321.
Dep r otection of th e Ben zyl Gr ou p s. A solution of benzy-
lated compound in MeOH/H2O (10:1) was treated with H2 at 60
psi in the presence of Pd(OH)2/C (Degussa type, 20% Pd(OH)2
on activated carbon) at 23 °C overnight. The reaction was filtered
through Celite and washed with MeOH/H2O/AcOH (10:1:1), and
the solvent was removed under reduced pressure.
2-[(1(S)-P h en ylet h yl)a m in o]-3-[2,3,4,6-t et r a b en zyl-r-D-
glu cop yr a n osyl]p r op a n en itr ile (2). The general procedure
was used for the synthesis. The desired pure (S)-derivative was
obtained. The (R)-aminonitrile was still contaminated with its
diastereoisomer (Table 1, entry 7:89% yield): 1H NMR (400 MHz,
CDCl3) S diastereoisomer (50.9%) δ 7.32-7.08 (m, 25H), 4.90-
4.30 (m, 8H), 4.20 (td, J ) 5.2 Hz J ) 3.9 Hz, 1H), 4.06 (q, J )
6.6 Hz, 1H), 3.75-3.55 (m, 5H), 3.37 (bd, J ) 9.3 Hz, 1H), 2.12
(m, 2H), 1.76 (bs, 1H), 1.33 (d, J ) 6.6 Hz, 3H); R diastereoisomer
(38.1% R/S ) 84/16) δ 7.32-7.08 (m, 25H), 4.90-4.30 (m, 8H),
3.98 (q, J ) 6.6 Hz, 1H), 3.84 (dd, J ) 8.2 Hz J ) 3.9 Hz, 1H),
3.75-3.55 (m, 5H), 3.48 (bd, J ) 8.8 Hz, 1H), 2.24 (ddd, J )
15.0 Hz J ) 11.6 Hz J ) 3.8 Hz, 1H), 2.01 (ddd, J ) 15.0 Hz J
) 8.1 Hz J ) 2.4 Hz, 1H), 1.27 (bs, 1H), 1.29 (d, J ) 6.6 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 144.75, 143.24, 138.5-137.7;
128.7-127.5, 126.73, 120.18, 119.94, 82.00, 81.98, 79.13, 79.98,
77.63, 77.42, 75.40, 75.02, 74.26, 71.78, 71.64, 70.95, 70.56, 68.54,
68.00, 56.52, 56.14, 45.29, 45.02, 29.69, 28.57. 24.73, 21.70;
HRMS (M + Na+) calcd for C45H48N2O5 719.3461, found 719.3479.
2(S)-[(1(S)-P h en yleth yl)a m in o]-3-[2,3,4,6-tetr a ben zyl-r-
D-glu cop yr a n osyl]p r op a n oic Acid (3). The general procedure
was used for the synthesis (93% yield): 1H NMR (600 MHz, CD3-
OD) δ 7.50-7.11 (m, 25H), 4.77 (d, J ) 11.4 Hz, 1H), 4.67 (m,
2H), 4.56 (AB system, νA ) 4.58 νB ) 4.53, J AB ) 11.4 Hz, 2H),
4.49 (m, 1H), 4.41 (m, 2H), 4.15 (btd, J ) 4.8 Hz J ) 10.4 Hz,
1H), 3.74 (m, 1H), 3.61 (m, 2H), 3.45 (m, 3H), 3.29 (m, 1H), 2.46
(btd, J ) 16.0 Hz J ) 5.1 Hz, 1H), 2.21 (bt, J ) 16.0 Hz, 1H),
2(S)-Am in o-3-r-L-fu cop yr a n osylp r op a n oic Acid (9). The
general procedure was used for the synthesis (94% yield): 1H
NMR (600 MHz, D2O) δ 4.11 (ddd, J ) 11.2, 5.6, 3.0 Hz, 1H),
3.94 (dd, J ) 9.7, 5.9 Hz, 1H), 3.91 (q, J ) 6.0 Hz, 1H), 3.79 (dd,
J ) 3.4, 1.6 Hz, 1H), 3.76 (bdd, J ) 9.6, 3.4 Hz, 2H), 2.26 (ddd,
J ) 15.3, 11.7, 3.5 Hz,), 1.94 (ddd, J ) 15.3, 12.0, 3.2 Hz, 1H),
1.11 (d, J ) 6.6 Hz, 3H); 13C NMR (150 MHz, D2O) δ 178.12,
71.02, 70.23, 69.11, 67.08, 66.69, 51.64, 25.19, 14.81; electrospray
(MH +) 236.

Notes
2(S)-[(1(S)-P h en yleth yl)a m in o]-3-[2,3,4,6-tetr a ben zyl-r-
J . Org. Chem., Vol. 65, No. 14, 2000 4443
138.23, 138.08, 128-126, 82.16, 79.53, 77.71, 75.43, 74.93, 73.42,
72.86, 71.50, 71.18, 68.43, 56.85, 55.88, 51.72, 29.26, 25.21;
HRMS (MaldiFTMS) calcd for C46H51N1O7 730.3744, found
730.3744.
L-fu cop yr a n osyl]p r op a n oic Acid , Meth yl Ester (10). The
general procedure was used for the synthesis (81% yield): 1H
NMR (600 MHz, CDCl3) δ 7.46-7.12 (m, 20H), 4.90-4.50 (m,
6H), 4.28 (td, J ) 11.5, 3.3 Hz, 1H), 3.91 (bs, 1H), 3.77 (bs, 1H),
3.79 (m, 1H), 3.71 (m, 6H), 3.11 (dd, J ) 9.3, 4.4 Hz, 1H), 1.95
(ddd, J ) 14.8, 10.8, 4.5 Hz, 1H), 1.63 (m, 2H), 1.29 (d, J ) 6.5
Hz, 3H), 1.16 (d, J ) 6.5 Hz, 3H); 13C NMR (150 MHz, CDCl3)
δ 177.62, 145.62, 139.67, 139.39, 139.23, 129-127, 77.77, 77.00,
74.24, 74.01, 73.91, 73.89, 73.85, 73.71, 69.22, 57.19, 57.00, 52.49,
26.48, 16.39; HRMS (M + Cs+) calcd for C39H45NO6 756.2301,
found 756.2321.
2(S)-[(1(S)-P h en yleth yl)a m in o]-3-[2,3,4,6-tetr a ben zyl-r-
D-glu cop yr a n osyl]p r op a n oic Acid , Meth yl Ester (11). The
general procedure was used for the synthesis (78% yield): 1H
NMR (400 MHz, CDCl3) δ 7.30-7.11 (m, 25H), 4.90 (m, 1H),
4.77 (m, 2H), 4.56 (m, 2H), 4.42 (m, 3H), 4.17 (td, J ) 5.2, 9.7
Hz, 1H), 3.73 (m, 2H), 3.68 (s, 3H), 3.66 (m, 2H), 3.61 (m, 2H),
3.43 (bd, J ) 9.4 Hz, 1H), 3.35 (dd, J ) 10.5, 1.9 Hz, 1H), 3.17
(t, J ) 6.2 Hz, 1H), 2.02 (m, 2H), 1.83 (bs, 1H), 1.31 (d, J ) 6.5
Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 175.79, 145.09, 138.66,
2(S)-Am in o-3-[r-D-glu cop yr a n osyl]p r op a n oic Acid Ace-
ta te Sa lt (12). The general procedure was used for the synthesis
except that 5% AcOH was added to the solvent mixture): 1H
NMR (600 MHz, D2O) δ 4.22 (btd, J ) 4.8, 10.1 Hz, 1H), 3.77
(m, 2H), 3.67 (dd, J ) 6.1, 9.7 Hz, 1H), 3.64 (dd, J ) 4.8 Hz, J AB
) 12.3 Hz, 1H), 3.56 (bt, J ) 9.2 Hz, 2H), 3.30 (t, J ) 9.2 Hz,
1H), 2.15 (m, 2H), 1.95 (); 13C NMR (150 MHz, CDCl3) δ 165.75,
74.48, 74.14, 73.70, 71.28, 70.71, 61.65, 54.07, 26.58, 23.77;
HRMS (MaldiFTMS) calcd for C9H18NO7 252.1083 (MH+), found
252.1079.
Su p p or tin g In for m a tion Ava ila ble: NMR spectra for
obtained compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
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