Facile synthesis of unusual glycosyl carbamates and amino acid glycosides from propargyl 1,2-orthoesters as glycosyl donors

Article abstract of DOI:10.1039/c1ob05056g

Propargyl 1,2-O-orthoesters are exploited for the synthesis of 1,2-trans O-glycosides of protected amino acids. N-Fmoc- and N-Cbz protected serine/threonine - benzyl/methyl esters reacted well with glucosyl-, galactosyl-, mannosyl- and lactosyl- derived propargyl 1,2-orthoesters affording respective 1,2-trans glycosides in good yields under AuBr₃/4 A MS Powder/CH₂Cl₂/rt. t-Boc serine derivative gave serine 1,2-orthoester and glycosyl carbamate. Optimized conditions enabled preparation of new glycosyl carbamates from N-Boc protected amines in a single step using gold catalysts and propargyl 1,2-orthoesters in excellent yields.

Full text of DOI:10.1039/c1ob05056g

Organic &
Biomolecular
Chemistry
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Volume 9 | Number 17 | 7 September 2011 | Pages 5881–6172
ISSN 1477-0520
FULL PAPER
Srinivas Hotha et al.
Facile synthesis of unusual glycosyl
carbamates and amino acid
glycosides from propargyl
1,2-orthoesters as glycosyl donors
1477-0520(2011)9:17;1-R

Organic &
Biomolecular
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PAPER
Facile synthesis of unusual glycosyl carbamates and amino acid glycosides
from propargyl 1,2-orthoesters as glycosyl donors†
Ashif Y. Shaikh,a Gopalsamy Sureshkumar,a Debasish Pati,b Sayam Sen Guptab and Srinivas Hotha*c
Received 10th January 2011, Accepted 9th March 2011
DOI: 10.1039/c1ob05056g
Propargyl 1,2-O-orthoesters are exploited for the synthesis of 1,2-trans O-glycosides of protected amino
acids. N-Fmoc- and N-Cbz protected serine/threonine - benzyl/methyl esters reacted well with
glucosyl-, galactosyl-, mannosyl- and lactosyl- derived propargyl 1,2-orthoesters affording respective
˚
1,2-trans glycosides in good yields under AuBr3/4 A MS Powder/CH2Cl2/rt. t-Boc serine derivative
gave serine 1,2-orthoester and glycosyl carbamate. Optimized conditions enabled preparation of new
glycosyl carbamates from N-Boc protected amines in a single step using gold catalysts and propargyl
1,2-orthoesters in excellent yields.
Saccharides glycosylated to an aglycone are termed as glycocon-
jugates and they play an important role in various biological
events and are classified in accordance with the type of attached
aglycone.1 For example, if the aglycone is a long chain fatty acid the
glycoconjugate is called a glycolipid2 whereas a protein attached
to a saccharide is known as a glycoprotein.3 Glycoproteins have
immense significance in a variety of biological processes including
cell signalling, inflammatory responses, neuronal development
and immune surveillance.4 Glycoproteins comprise a saccharide
attached to the protein through an N-atom or an O-atom and
are named N- or O-glycosides (Fig. 1). Furthermore, it has
been shown that glycosylated peptides (or antifreeze peptides)
Fig. 1 General glycosides and amino acid glycosides.
are valuable for the survival of aquatic marine life at sub zero
temperatures in the Antarctic region.5 In mammalians, blood
group determinants, tumor associated antigens and a host of
other significant biological events involve glycoproteins.6 Thus,
synthetic glycopeptides are required for improving our current
understanding of those biological events which involve them.
At the heart of any glycopeptide synthesis, the attachment of
the sugar residue(s) to the amino acid as a glycoside from a
suitable saccharide and a protected amino acid is the key event.
However, only a limited number of approaches are available for the
attachment of a serine/threonine.7 For example, one of the earliest
and widely used methods couples the CbzSer(OH)Bn and an
acetobromosugar by means of environmentally detrimental mer-
cury salts. A notable and significant improvement was reported7a
by Cameron’s group taking advantage of reaction conditions
developed by Field et al.7c In this premise, methods that enable
preparation of amino acid glycosides from stable glycosyl donors
using catalytic and eco-friendly reagents are essential.8
Recent serendipitous observations from our laboratory led
to the identification of propargyl glycosides as novel glycosyl
donors for transglycosylations exploiting AuCl3 in acetonitrile at
60 ◦C.9a Later on, propargyl 1,2-orthoesters were found to afford9d
˚
1,2-trans glycosides under AuBr3/CH2Cl2/4 A MS powder/rt
and subsequent temperature controlled experiments revealed that
propargyl 1,2-orthoesters can be activated9c in the presence of
propargyl glycosides to obtain propargyl disaccharides.9
In continuation of the programme on gold catalyzed
glycosylations,9 we got interested in the exploitation of propar-
gyl 1,2-O-orthoesters9h for the synthesis of amino acid glyco-
conjugates. To begin our investigation, initially, propargyl 1,2-
orthoesters, Fmoc- and Cbz-protected serine/threonine were con-
sidered. Accordingly, per-O-benzoylated glucose 1,2-O-orthoester
1a was allowed to react with serine derived aglycone glycosides.
Among various naturally occurring amino acids, hydroxyl
containing serine and threonine and their Fmoc-, Cbz- and
Boc-protected derivatives are the most widely used. Thus,
aDivision of Organic Chemistry, Combi Chem – Bio Resource Center,
National Chemical Laboratory, Pune, 411008, India
bChemical Engineering & Process Development, National Chemical Labo-
ratory, Pune, 411 008, India
cDepartment of Chemistry, Indian Institute of Science Education & Research,
Pune, 411 021, India. E-mail: s.hotha@iiserpune.ac.in; Fax: +91 20 2589
9697; Tel: +91 20 2590 8000
† Electronic supplementary information (ESI) available: General experi-
mental techniques and NMR spectral charts for all compounds. See DOI:
10.1039/c1ob05056g
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CbzSer(OH)Bn (2a) reacted in the presence of 7 mol% of
AuBr3/CH2Cl2/4 A MS powder/rt/30 min to afford serine
efficiently polymerize into glycopolypeptides.12a Therefore, we
attempted the synthesis of the natural D-glucose-L-serine polypep-
tide (7b) from the serine O-glucoside 3a. The synthesis of the
gluco-NCA was carried out in two steps: first, we subjected
the glycoconjugate 3a to hydrogenolysis using 10% Pd/C at
400 psi to obtain per-O-benzoylated-D-glucose-L-serine which
was subsequently converted to its corresponding NCA 7a using
triphosgene and a-pinene7a in 80% yield after three crystallizations
(Scheme 2). Polymerization of 7a was attempted using hexylamine
as the initiator (M/I = 20) in dry DMF (Scheme 2). The progress
of the polymerization was followed by monitoring the complete
disappearance (24 h) of the anhydride stretch of the NCA ring
at 1787 and 1852 cm-1 in FT-IR. The resultant polymer 7b
was purified by reprecipitation. The number average molecular
weight (Mn) of the precipitated polymer 7b was estimated to be
13,600 Da by GPC (expected molecular weight 13,400) and a
molecular weight distribution with a PDI of 1.1 was observed.
The structure of the resulting polymer 7b was identified by 1H and
13C NMR spectral analysis.10 The overall strategy can be applied
to obtain glycosyl NCAs and eventually glycopolypeptides.12b
Such glycopolypeptides, featuring synthetic macromolecules with
pendant carbohydrate moieties, can find widespread applications
in various fields such as macromolecular drugs and drug delivery
systems, hydrogels, matrices for controlled cell culture, and as
models of biological systems.
˚
glucoside 3a (Scheme 1).10 The literature indicated that several
attempts have been made to synthesize amino acid glycosides
that included use of toxic Hg salts, very extensive and labo-
rious purification protocols which led to a poor overall yield
of the resulting glycoconjugate.7a,d However, AuBr3 catalyzed
glycosylation resulted in the isolation of 76% of the amino acid
glycoconjugate. Simple gravity flow and conventional silica gel
column chromatography would be sufficient to separate propargyl
2,3,4,6-tetra-O-benzoyl-b-D-glucopyranoside (sole byproduct)9d,e
from the required serine glucoside 3a. 1,2-trans Glycosidic linkage
was confirmed by NMR spectral studies wherein the anomeric
proton was noticed at d 4.78 ppm (d, 1H, J = 7.6 Hz) and the
anomeric carbon was observed at the d101.3 ppm.10
Scheme 1 Synthesis of amino acid glycoconjugates.
We then continued our synthesis endeavour with 1,2-orthoester
1a that was allowed to react with FmocThr(OH)OMe (2b) to
give the threoninyl glucoside (3b) in good yield. Furthermore,
CbzThr(OH)Bn (2c) reacted with the glycosyl donor 1a result-
ing in the formation of threoninyl glucoside 3c (Scheme 1).
It is interesting to note that the N-Cbz- or N-Fmoc-groups
and benzyl/methyl esters were intact during the gold catalyzed
glycosylation.10 Versatility of the glycosylation methodology with
gold reagents was further extended to the other glycosyl donors.
For example, galactosyl (1b), mannosyl (1c) and lactosyl (1d) 1,2-
orthoesters were allowed to react with serine and threonine derived
aglycones (2a–2d) to obtain corresponding galactosides (4a–4c),
mannosides (5a–5c) and lactosides (6a–6c) respectively in good
yields (Table 1). In all the cases, we identified formation of 1,2-
trans selective glycosides only.10
A very important application of these synthesized serine
O-glycosides is that they can be easily converted to their cor-
responding N-carboxyanhydride (NCA), which in turn can be
subjected to ring-opening polymerization to afford glycopolypep-
tides. The synthesis of glycopolypeptides using the ring-opening
polymerization of O-linked glycoserine NCA has been known for
a long time.11 However, the synthesis of the NCA monomer was
very inefficient and required the usage of toxic Hg salts for the key
glycosylation step. An improved synthesis of serine O-glycoside
NCA was reported by Cameron et al.
Scheme 2 Synthesis of N-carboxyanhydride and glycopeptide. Reagents:
(1) Pd/C, H2, CH3OH, 400 psi, 4 h; (2) Triphosgene, a-pinene, THF, 50 ◦C,
2 h; (3) Hexylamine (0.05 eq), ‘proton sponge’ (0.25 eq), DMF, rt, 24 h.
tert-Butoxy carbamates (t-Boc) of serine/threonine are also
frequently used in the glycopeptide synthesis.3 Thus a model gold
catalyzed glycosylation was performed between 1,2-orthoester (1a)
and BocSer(OH)OMe (2e). The required amino acid glucoside
was not observed and instead, surprisingly an orthoester A
was obtained in 27% yield; the major compound being a O-
linked glucosyl carbamate (8). The structure of orthoester A
and carbamate 8 was assigned after thorough characterization
(Scheme 3).10 For example, anomeric proton of compound A was
noticed at d 6.01 ppm as a doublet (J = 5.2 Hz) along with anomeric
and quaternary carbons at d 97.6 and 121.1 ppm respectively.
However no polymerization of these monomers has been re-
ported to date except a recent report wherein Kramer and Deming
have reported the synthesis of the non-natural glycosylated-
L-lysine-N-carboxyanhydride (glyco-K NCA) monomers which
Scheme 3 Glucosyl carbamates from propargyl 1,2-orthoesters.
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Table 1 Synthesis of amino acid O-glycosides
Glycosyl donor Glycosyl acceptor
Glycoconjugate
Time/ h
1.0
Yield (%)
63
2a
2.0
1.0
2.0
67
69
62
2c
2a
2b
2c
2a
2.0
2.0
2.0
66
62
61
2d
2b
2.0
2.0
63
64
Structural integrity of compound 8 was confirmed as the 1,2-
trans O-carbamate since the anomeric proton was identified in a
more deshielded region at d 6.06 ppm as a doublet (J = 8.4 Hz)
and concurrently the anomeric carbon was noticed at d 93.5
ppm.10 This unexpected set back was attributed to acidic reaction
conditions and hence it has been envisioned that strong Lewis and
Brønsted acids would facilitate the glycoside formation.9 But the
presence of the acid labile t-Boc group posed a serious hurdle in
this direction.
Formation of glucosyl carbamate can be ascribed to reaction
conditions that facilitated the cleavage of the tertiary butyl
group thereby producing a reactive carbamic acid.13a Usually
carbamic acids liberate carbon dioxide to afford corresponding
amines; however, in this situation, carbamic acid trapped the
in situ generated oxocarbenium ion from 1a to give glucosyl
carbamate. This peculiar observation was further corroborated, as
the t-Boc protected phenylalanine also reacted with the glycosyl
donor 1a to give glucosyl carbamate 10a in 65% yield.10 Less
Brønsted acidic and alkynophilic AuCl3 did not improve the
performance of the reaction as the release of HCl will not be
facile in an aprotic medium; nevertheless, near quantitative yield
of compound 10a was obtained in 2 h with a catalytic amount of
HAuCl4 (Scheme 3).10 Similar cleavage of the t-butyl group and
intramolecular cyclization was observed when N-Boc protected
alkynylamines were treated with gold reagents to give alkylidene
2-oxazolidinones.13b,c
The unusual formation of the carbamate linkage needs a special
mention. Glycosyl carbamates are important because of their
stability to alkaline conditions13a and some of them are reported
to act as glycosyl donors.13d,e In addition, glycosyl carbamates are
studied as dopamine prodrugs13f,g and surfactants.13h Recently, car-
bamate linkages were explored for studying carbohydrate–protein
interactions13i and also for ligation.13j Glycosyl carbamates can be
prepared by a reaction of corresponding lactol and an isocyanate13l
in the presence of a base13d or from glycosyl carbonates.13k TM-
SOTf catalyzed reaction of glycosyl trichloroacetimidates perhaps
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Table 2 Synthesis of glycosyl carbamates
Glycosyl donor
Acceptor
Product
Yield (%)
98
1a
BocNHCH3 9c
96
99
95
94
97
98
1b
9a
9b
1c
9a
9b
98
95
1d
9a
9b
95
96
gives easy access but in moderate to good yields depending on
the type of substrate.13a Thus, methods that enable easy synthesis
of glycosyl carbamates without the use of toxic isocyanates from
stable glycosyl donors are invaluable. The foregoing discussion
clearly highlights the merit of HAuCl4 catalyzed synthesis of
glucosyl carbamate from stable propargyl 1,2-orthoester as a
glycosyl donor.
of alicyclic (9b), aliphatic (9c, 9d) and aromatic (9e,9f) reacted with
glucose 1,2-orthoester 1a to afford their respective carbamates
10b–10f (Table 2).10 Furthermore, galactosyl- (1b), mannosyl-
(1c) and lactosyl- (1d) derived propargyl 1,2-orthoesters (1d) also
participated successfully in the glycosylation reaction to afford the
corresponding 1,2-trans glycosides 11a–b, 12a–b and 13a–b in near
quantitative yields (Table 2).
The generality of the methodology has been verified by using a
panel of t-Boc protected amines. Boc-protected amino compounds
In conclusion, a new method for the synthesis of amino
acid glycoconjugates is described which is more applicable to
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Cbz- and Fmoc-protected amino acid Me/benzyl esters. Boc-
protected serine derivative was found to give serine 1,2-orthoester
in poor yield and the major compound was found to be the gly-
cosyl carbamate. Optimized reaction conditions showed HAuCl4
gave glycosyl carbamates in excellent yields. The generality of
the methodology was evaluated using various glycosyl donors,
aglycones and building blocks. Several opportunities as a result
of the easy access to this novel glycosidic linkage are currently
underway.
the reaction (24 h), an aliquot was removed for GPC analysis. The
solvent was removed under reduced pressure and the residue was
redissolved in CH2Cl2 and the polymer was precipitated out by
the addition of methanol. The precipitated polymer was collected
by centrifugation and dried to afford white glycopolypeptide 7b in
90% yield.
Compound characterization data
Benzyl N-(benzyloxycarbonyl)-O-(2,3,4,6-tetra-O-benzoyl-b-D-
glucopyranosyl)-L-serinate (3a). [a]2D5 = +14.0 (c = 1.0, CHCl3);
1H NMR (200.13 MHz, CDCl3): d = 3.91(dd, J = 3.4, 10.3 Hz, 1
H), 4.01(ddd, J = 3.3, 4.9, 8.3 Hz, 1 H), 4.32–4.56(m, 3H), 4.61(dd,
J = 3.2, 12.2 Hz, 1 H), 4.78(d, J = 7.6 Hz, 1 H), 4.99(dd, J = 12.3,
19.4 Hz, 2 H), 5.13(dd, J = 12.3, 14.3 Hz, 2 H), 5.45(dd, J = 7.8,
9.5 Hz, 1 H), 5.61(m, 2H), 5.86(t, J = 9.6 Hz, 1 H), 7.20–7.58(m,
22H), 7.78–8.05(m, 8H); 13C NMR (50.32 MHz, CDCl3): d = 54.2,
62.9, 66.9, 67.4, 69.3, 69.4, 71.7, 72.2, 72.5, 101.3, 128.0–129.8,
133.1, 133.2, 133.3, 133.4, 135.2, 136.2, 155.8, 165.1, 165.1, 165.7,
166.1, 169.2; Anal. Calcd for C52H45NO14: C, 68.79; H, 5.00; N,
1.54; Found: C, 67.87; H, 5.21; N, 1.66; HRMS (MALDI-TOF):
m/z calcd for C52H45NO14+Na: 930.2738, Found: 930.2742.
Experimental
General procedure for the synthesis of amino acid glycosides. To
a solution of glycosyl donor (0.1 mmol) and aglycone (0.1 mmol)
˚
in anhydrous CH2Cl2 (5 mL) was added 4 A MS powder (50 mg
0.1 mmol-1) and 7 mol% of AuBr3 under argon atmosphere at room
temperature. The resulting mixture was stirred till the completion
of the reaction as judged by TLC analysis. The reaction mixture
was concentrated in vacuo to obtain a crude residue which was
purified by conventional silica gel column chromatography using
ethyl acetate–petroleum ether as mobile phase.
General procedure for the synthesis of glycosyl carbamates
from propargyl 1,2-orthoesters. To a solution of glycosyl donor
Methyl N-(9-Fluorenylmethoxycarbonyl)-O-(2,3,4,6-tetra-O-
benzoyl-b-D-glucopyranosyl)-L-threoninate (3b). [a]2D5 = +12.0
(c = 1.0, CHCl3); 1H NMR (200.13 MHz, CDCl3): d = 1.14(d, J =
6.3 Hz, 3 H), 3.71(s, 3 H), 4.05–4.58(m, 7 H), 4.65(dd, J = 3.3,
12.2 Hz, 1 H), 4.87(d, J = 7.7 Hz, 1 H), 5.48(dd, J = 8.0, 9.7 Hz,
1 H), 5.69(m, 2 H), 5.91(t, J = 9.7 Hz, 1 H), 7.20–7.65(m, 20 H),
7.72–8.06(m, 8 H); 13C NMR (50.32 MHz, CDCl3): d = 16.9,
47.0, 52.5, 58.4, 62.8, 67.3, 69.4, 71.8, 72.1, 72.6, 75.1, 99.3, 119.9,
125.2, 127.0–128.8, 133.2, 133.3, 133.3, 133.4, 141.1, 141.2, 143.6,
143.9, 156.7, 165.1, 165.1, 165.7, 166.1, 170.5; Anal. Calcd for
C54H47NO14: C, 69.44; H, 5.07; N, 1.50; Found: C, 69.18; H, 5.22;
N, 1.80; HRMS (MALDI-TOF): m/z Calcd for C54H47NO14+Na,
956.2894; Found, 956.2889.
(0.1 mmol) and t-Boc protected amine (0.1 mmol) in anhydrous
-1
˚
CH2Cl2 (5 mL) was added 4 A MS powder (50 mg 0.1 mmol ) and
5 mol% of HAuCl4 under argon atmosphere at room temperature.
The resulting mixture was stirred till the completion of the reaction
as judged by TLC analysis (2 h). The reaction mixture was
concentrated in vacuo to obtain a crude residue which was purified
by conventional silica gel column chromatography using ethyl
acetate–petroleum ether as mobile phase.
General procedure for the glyco N-carboxyanhydrides (7a).
Hydrogenolysis of compounds 3a was carried out using 10% Pd/C
in MeOH–EtOAc (9 : 1) at 400 psi for 12 h. After completion of
the reaction, the reaction mixture was filtered and concentrated
under reduced pressure to afford per-O-benzoylated-D-glucose-L-
serine in almost quantitative yield. The resulting compounds were
directly used for NCA synthesis without any further purification.
Benzyl N-(benzyloxycarbonyl)-O-(2,3,4,6-tetra-O-benzoyl-b-D-
glucopyranosyl)-L-threoninate (3c). [a]2D5 = +4.0 (c = 1.0, CHCl3);
1H NMR (200.13 MHz, CDCl3): d = 1.11(d, J = 6.3 Hz, 3 H),
3.86(td, J = 3.5, 9.4 Hz, 1 H), 4.30–4.59(m, 4 H), 4.74(d, 1 H, J =
8.0 Hz), 5.04(s, 2 H), 5.18(s, 2 H), 5.38(dd, J = 8.0, 9.6 Hz, 1 H),
5.62(m, 2 H), 5.80(t, J = 9.5 Hz, 1 H), 7.20–7.58(m, 22 H), 7.79–
8.05(m, 8 H); 13C NMR (50.32 MHz, CDCl3): d = 17.0, 58.4, 62.6,
66.9, 67.2, 69.2, 71.9, 72.0, 72.5, 75.0, 99.0, 127.8–129.7, 133.1,
133.2, 133.3, 133.4, 135.4, 136.2, 156.7, 165.0, 165.0, 165.7, 166.0,
169.8; Anal. Calcd for C53H47NO14: C, 69.05; H, 5.14; N, 1.52;
Found: C, 68.64; H, 5.76; N, 1.77; HRMS (MALDI-TOF): m/z
Calcd. for C53H47NO14+Na, 944.2894; Found, 944.2899.
To
a
solution of per-O-benzoylated-D-glucose-L-serine
(0.1 mmol) in freshly distilled anhydrous tetrahydrofuran (30 mL)
was added a solution of triphosgene (0.05 mmol) in anhydrous
tetrahydrofuran (5 mL) under argon atmosphere. a-Pinene
(0.15 mmol) was added and the reaction mixture was heated to
◦
50 C for 2 h and cooled to room temperature, poured into dry
hexane. The white precipitate of the N-carboxyanhydride (7a)
was vacuum filtered quickly and reprecipitated (2¥) by dissolving
in ethyl acetate followed by addition of light petroleum. The
resulting precipitate was filtered and dried under vacuum (Yield
80%).
Benzyl N-(benzyloxycarbonyl)-O-(2,3,4,6-tetra-O-benzoyl-b-D-
galactopyranosyl)-L-serinate (4a). [a]2D5 = +58.0 (c = 1.0, CHCl3);
1H NMR (200.13 MHz, CDCl3): d = 3.98(dd, J = 3.2, 10.4 Hz, 1
H), 4.19(m, 2 H), 4.32–4.80(m, 4 H), 5.00(q, J = 12.3, 17.7 Hz, 2
H), 5.17(q, J = 12.4, 17.3 Hz, 2 H), 5.56(m, 1 H), 5.73(m, 2 H),
5.96(m, 1 H), 7.20–7.68(m, 22 H), 7.74–8.11(m, 8 H); 13C NMR
(50.32 MHz, CDCl3): d = 54.3, 61.8, 66.9, 67.4, 67.9, 69.4, 69.5,
71.4, 71.4, 101.8, 127.9–130.0, 133.2, 133.3, 133.3, 133.6, 135.2,
136.1, 155.8, 165.2, 165.4, 165.5, 166.0, 169.3; Anal. Calcd for
C52H45NO14: C, 68.79; H, 5.00; N, 1.54; Found: C, 67.86; H, 5.18;
Procedure for the synthesis of glycopolymer (7b). To a 2 mL
solution of glyco-N-carboxyanhydride (7a) (200 mg, 0.28 mmol) in
anhydrous DMF was added 1,8-bis(dimethylamino)naphthalene
(0.07 mmol; 1 M) [‘proton sponge’] as an additive and hexylamine
(14 mL, 1.0 mmol mL-1) as an initiator inside the glove box.
The progress of the polymerization was monitored by FT-IR
spectroscopy by comparing with the intensity of the initial NCA’s
anhydride stretching at 1789 cm-1 and 1852 cm-1. At the end of
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N, 1.62; HRMS (MALDI-TOF): m/z Calcd for C52H45NO14+Na,
930.2738; Found, 930.2735.
Benzyl N-(benzyloxycarbonyl)-O-(2,3,4,6-tetra-O-benzoyl-a-D-
mannopyranosyl)-L-threoninate (5c). [a]2D5 = -40.0 (c = 1.0,
CHCl3); 1H NMR (200.13 MHz, CDCl3): d = 1.42(d, J = 6.2 Hz,
3 H), 4.42–4.55(m, 3 H), 4.57–4.71(m, 2 H), 5.07(d, J = 1.8 Hz,
1 H), 5.19(s, 2 H), 5.31(s, 2 H), 5.45(dd, J = 1.8, 3.1 Hz, 1 H),
5.72–5.85(m, 2 H), 6.06(t, J = 9.9 Hz, 1 H), 7.21–7.68(m, 22 H),
7.82–8.10(m, 8 H); 13C NMR (50.32 MHz, CDCl3): d = 18.3, 58.8,
62.9, 66.8, 67.3, 67.9, 69.6, 69.7, 70.5, 77.9, 99.0, 128.1–129.9,
133.1, 133.1, 133.5, 133.5, 135.0, 136.1, 156.7, 165.2, 165.2, 165.4,
166.1, 169.9; Anal. calcd for C53H47NO14: C, 69.05; H, 5.14; N,
1.52; Found: C, 69.51; H, 4.67; N, 1.02; HRMS (MALDI-TOF):
m/z Calcd for C53H47NO14+Na, 944.2894; Found, 944.2897.
Methyl N-(9-Fluorenylmethoxycarbonyl)-O-(2,3,4,6-tetra-O-
benzoyl-b-D-galactopyranosyl)-L-serinate (4b). [a]D25
= +66.0
1
(c = 1.0, CHCl3); H NMR (200.13 MHz, CDCl3): d = 3.68(s,
3 H), 3.94(dd, J = 3.4, 10.4 Hz, 1 H), 4.14(t, J = 6.9 Hz, 1 H),
4.25–4.52(m, 6 H), 4.63(dd, J = 6.5, 11.1 Hz, 1 H), 4.73(d, J =
7.6 Hz, 1 H), 5.52(d, J = 8.1 Hz, 1 H), 5.60(dd, J = 3.3, 10.2 Hz,
1 H), 5.75(dd, J = 7.8, 10.2 Hz, 1 H), 6.00(d, J = 3.3 Hz, 1 H),
7.20–7.66(m, 20 H), 7.75–8.11(m, 8 H); 13C NMR (50.32 MHz,
CDCl3): d = 47.1, 52.7, 54.3, 61.9, 66.7, 67.9, 69.4, 69.4, 71.4, 71.4,
101.8, 119.9–130.0, 133.2, 133.3, 133.3, 133.6, 141.3, 141.3, 143.7,
143.8, 155.7, 165.2, 165.5, 165.5, 166.0, 169.8; Anal. Calcd for
C53H45NO14: C, 69.20; H, 4.93; N, 1.52; Found: C, 67.94; H, 4.02;
N, 1.66; HRMS (MALDI-TOF): m/z Calcd for C53H45NO14+Na,
942.2738; Found, 942.2736.
Benzyl N-(benzyloxycarbonyl)-O-[2,3,6-tri-O-benzoyl-4-O-(2,3,
4,6-tetra-O-benzoyl-b-D-galactopyranosyl)-b-D-glucopyransyl]-L-
1
serinate (6a). [a]2D5 = +46.0 (c = 1.0, CHCl3); H NMR (200.13
MHz, CDCl3): d = 3.59(d, J = 9.7 Hz, 1 H), 3.70(d, J = 6.5 Hz, 2
H), 3.78–3.92(m, 2 H), 4.18(t, J = 9.7 Hz, 1 H), 4.26(dd, J = 2.6,
10.4 Hz, 1 H), 4.36–4.59(m, 4 H), 4.81–4.98(m, 3 H), 5.06(s, 2 H),
5.32–5.45(m, 2 H), 5.52(d, J = 8.0 Hz, 1 H), 5.69(d, J = 9.2 Hz,
2 H), 5.75(d, J = 6.2 Hz, 1 H), 7.11–7.64(m, 31 H), 7.69–8.02(m,
14 H); 13C NMR (100.61 MHz, CDCl3): d = 54.2, 61.0, 62.1, 66.9,
67.3, 67.5, 69.4, 69.8, 71.3, 71.5, 71.7, 72.5, 73.0, 75.6, 100.9, 101.3,
128.0–130.0, 133.1, 133.2, 133.3, 133.4, 133.4, 133.5, 133.5, 135.1,
136.2, 155.8, 164.8, 165.1, 165.2, 165.3, 165.4, 165.6, 165.8, 169.2;
Anal. calcd for C79H67NO22: C, 68.64; H, 4.89; N, 1.01; Found: C,
68.36; H, 4.38; N, 1.12; HRMS (MALDI-TOF): m/z Calcd for
C79H67NO22+Na, 1404.4052; Found, 1404.4048.
Benzyl N-(benzyloxycarbonyl)-O-(2,3,4,6-tetra-O-benzoyl-b-D-
galactopyranosyl)-L-threoninate (4c). [a]2D5 = +36.0 (c = 1.0,
CHCl3); 1H NMR (200.13 MHz, CDCl3): d = 1.14(d, J = 6.4 Hz,
3 H), 4.06(t, J = 6.4 Hz, 1 H), 4.31(dd, J = 7.1, 11.3 Hz, 1 H),
4.43(dd, J = 2.2, 9.3 Hz, 1 H), 4.48–4.61(m, 2 H), 4.71(d, J =
7.8 Hz, 1 H), 5.07(s, 2 H), 5.24(s, 2 H), 5.51(dd, J = 3.3, 10.4 Hz,
1 H), 5.61–5.75(m, 2 H), 5.92(d, J = 3.8 Hz, 1 H), 7.19–7.66(m, 22
H), 7.75–8.08(m, 8 H); 13C NMR (50.32 MHz, CDCl3): d = 17.4,
58.5, 61.6, 67.0, 67.3, 67.8, 69.8, 71.1, 71.3, 75.6, 99.9, 127.8–130.0,
133.2, 133.3, 133.3, 133.5, 135.4, 136.2, 156.7, 165.2, 165.5, 165.5,
165.9, 169.9; Anal. calcd for C53H47NO14: C, 69.05; H, 5.14; N,
1.52; Found: C, 66.49; H, 4.95; N, 1.35; HRMS (MALDI-TOF):
m/z Calcd for C53H47NO14+Na, 944.2894; Found, 944.2890.
Methyl N-(9-Fluorenylmethoxycarbonyl)-O-[2,3,6-tri-O-benz-
oyl-4-O-(2,3,4,6-tetra-O-benzoyl-b-D-galactopyranosyl)-b-D-glu-
1
copyranosyl]-L-serinate (6b). [a]2D5 = +48.0 (c = 1.0, CHCl3); H
NMR (500.13 MHz, CDCl3): d = 3.58(s, 3 H), 3.71(d, J = 6.4 Hz, 2
H), 3.80(m, 2 H), 3.91(t, J = 6.7 Hz, 1 H), 4.11(t, J = 6.7 Hz, 1 H),
4.20–4.35(m, 3 H), 4.41(m, 1 H), 4.48(dd, J = 4.3, 12.3 Hz, 2 H),
4.59(m, 2 H), 4.88(d, J = 7.9 Hz, 1 H), 5.38–5.45(m, 2 H), 5.48(d,
J = 7.9 Hz, 1 H), 5.73–5.85(m, 3 H), 7.11–8.02(m, 43 H); 13C NMR
(125.76 MHz, CDCl3): d = 47.1, 52.6, 54.2, 61.0, 62.1, 66.8, 67.4,
69.4, 69.8, 71.3, 71.4, 71.6, 72.5, 73.0, 75.7, 101.0, 101.3, 120.0,
125.0, 125.1, 126.9–130.0, 133.2, 133.3., 133.4, 133.4, 133.5, 141.2,
141.3, 143.6, 143.7, 155.7, 164.8, 165.1, 165.2, 165.2, 165.4, 165.5,
165.8, 169.7; Anal. calcd for C80H67NO22: C, 68.79; H, 5.00; N,
1.54; Found: C, 68.21; H, 5.58; N, 1.49; HRMS (MALDI-TOF):
m/z Calcd for C80H67NO22+Na, 1416.4052; Found, 1416.4056.
Benzyl N-(benzyloxycarbonyl)-O-(2,3,4,6-tetra-O-benzoyl-a-D-
mannopyranosyl)-L-serinate (5a). [a]2D5 = -42.0 (c = 1.0, CHCl3);
1H NMR (200.13 MHz, CDCl3): d = 4.14(d, J = 2.7 Hz, 2 H),
4.32–4.68(m, 4 H), 4.99(d, J = 1.6 Hz, 1 H), 5.14(d, J = 1.5 Hz, 2
H), 5.32(dd, J = 12.1, 20.5 Hz, 2 H), 5.59(dd, J = 1.8, 3.2 Hz, 1 H),
5.79(dd, J = 3.2, 10.1 Hz, 1 H), 5.96(d, J = 7.9 Hz, 1 H), 6.09(t, J =
10.1 Hz, 1 H), 7.20–7.65(m, 22 H), 7.81–8.14(m, 8 H); 13C NMR
(50.32 MHz, CDCl3): d = 54.5, 62.6, 66.5, 67.2, 67.8, 67.9, 69.4,
69.7, 70.1, 98.4, 128.1–129.9, 133.0, 133.1, 133.4, 133.5, 135.0,
136.0, 155.9, 165.2, 165.3, 165.4, 166.1, 169.5; Anal. calcd for
C52H45NO14: C, 68.79; H, 5.00; N, 1.54; Found: C, 68.21; H, 5.58;
N, 1.49; HRMS (MALDI-TOF): m/z Calcd for C52H45NO14+Na,
930.2738; Found, 930.2740.
Methyl N-(9-Fluorenylmethoxycarbonyl)-O-[2,3,6-tri-O-benz-
oyl-4-O-(2,3,4,6-tetra-O-benzoyl-b-D-galactopyranosyl)-b-D-glu-
copyranosyl]-L-threoninate (6c). [a]2D5 = +42.0 (c = 1.0, CHCl3); 1H
NMR (400.13 MHz, CDCl3): d = 1.11(d, J = 6.4 Hz, 3 H), 3.57(s,
3 H), 3.70–3.86(m, 3 H), 3.94(t, J = 6.6 Hz, 1 H), 4.13–4.45(m,
6 H), 4.52(dt, J = 3.9, 12.9 Hz, 1 H), 4.61(ABq, J = 14.9 Hz, 1
H), 4.85(ABq, J = 8.0 Hz, 2 H), 5.44(m, 2 H), 5.69(d, J = 9.3 Hz,
1 H), 5.73–5.87(m, 3 H), 7.12–8.13(m, 43 H); 13C NMR (100.61
MHz, CDCl3): d 16.8, 47.0, 52.3, 58.4, 61.0, 62.1, 67.3, 67.5, 69.9,
71.4, 71.7, 72.6, 73.0, 74.9, 75.7, 77.2, 99.0, 101.0, 119.9, 125.2,
127.0–129.9, 133.2, 133.3, 133.4, 133.5, 133.5, 141.1, 141.2, 143.6,
143.9, 156.7, 164.8, 165.2, 165.2, 165.3, 165.4, 165.5, 165.8, 170.4;
Anal. calcd for C81H69NO22: C, 69.08; H, 4.94; N, 0.99; Found: C,
67.51; H, 5.02; N, 0.69; HRMS (MALDI-TOF): m/z Calcd for
C81H69NO22+Na, 1430.4209; Found, 1430.4212.
Methyl N-(9-Fluorenylmethoxycarbonyl)-O-(2,3,4,6-tetra-O-
benzoyl-a-D-mannopyranosyl)-L-threoninate (5b). [a]2D5 = -30.0
1
(c = 1.0, CHCl3); H NMR (200.13 MHz, CDCl3): d = 1.43(d,
J = 6.2 Hz, 3 H), 3.90(s, 3 H), 4.33(dd, J = 7.1, 14.4 Hz, 2
H), 4.28–4.75(m, 6 H), 5.17(d, J = 1.5 Hz, 1 H), 5.50(dd, J =
1.8, 3.1 Hz, 1 H), 5.75–5.95(m, 2 H), 6.10(t, J = 9.6 Hz, 1 H),
7.20–8.10(m, 28 H); 13C NMR (50.32 MHz, CDCl3): d = 18.2,
47.1, 53.0, 58.6, 62.9, 66.9, 67.5, 69.4, 69.6, 70.5, 77.8, 99.0, 119.9,
125.2, 127.1–129.8, 133.1, 133.2, 133.5, 133.5, 141.3, 141.3, 143.7,
143.8, 156.7, 165.3, 165.5, 165.5, 166.1, 170.5; Anal. calcd for
C54H47NO14: C, 69.44; H, 5.07; N, 1.50; Found: C, 66.42; H, 4.20;
N, 1.34; HRMS (MALDI-TOF): m/z Calcd for C54H47NO14+Na,
956.2894; Found, 956.2893.
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The Royal Society of Chemistry 2011
©

O-(2,3,4,6-tetra-O-benzoyl-b-D-glucopyranosyl)-N-carboxy-L-
165.1, 165.3, 165.6, 166.1; HRMS (MALDI-TOF): m/z Calcd for
C45H43NO11+Na, 796.2734; Found, 796.2730.
1
serine anhydride (7a). IR(cm-1): 1854, 1789; H NMR (500.13
MHz, CDCl3): d = 3.92(dd, J = 5.8, 11.0 Hz, 1H), 4.11(t, J =
9.0 Hz, 2H), 4.26–4.35(m, 2H), 4.85(d, J = 7.6 Hz, 1H), 4.90(d,
J = 12.2 Hz, 1H), 5.40(t, J = 9.5 Hz, 1H), 5.66(t, J = 9.5 Hz, 1H),
5.84(t, J = 9.8 Hz, 1H), 6.69(s, 1H), 7.15–7.54(m, 12H), 7.70(d,
J = 7.4 Hz, 2H), 7.86(d, J = 7.2 Hz, 2H), 7.87(d, J = 7.2 Hz, 2H),
8.03(d, J = 7.6 Hz, 2H); 13C NMR (125.76 MHz, CDCl3): d = 58.5,
62.1, 68.6, 68.7, 71.2, 72.4, 73.2, 101.2, 128.3–130.0, 133.3, 133.5,
133.6, 133.6, 151.5, 165.1, 165.2, 165.7, 166.7, 167.1; MS (ESI):
m/z: calcd for [C38H31NO13+Na]+: 732.641; found: 732.145.
N -(2,3,4,6-tetra-O-Benzoyl-b-D-glucopyranosyloxycarbonyl)-
1
methylamine (10c). [a]2D5 = +47.6 (c = 1.0, CHCl3); H NMR
(200.13 MHz, CDCl3): d = 2.74(d, J = 4.9 Hz, 3 H), 4.31(qd, J =
3.0, 4.3, 7.3 Hz, 1 H), 4.48(dd, J = 4.4, 12.3 Hz, 1 H), 4.64(dd, J =
2.8, 12.3 Hz, 1 H), 4.92(q, J = 4.7, 9.6 Hz, 1 H), 5.66(dd, J = 8.3,
9.6 Hz, 1 H), 5.76(t, J = 9.6 Hz, 1 H), 5.97(t, J = 9.6 Hz, 1 H), 6.05(d,
J = 8.1 Hz, 1 H), 7.24–7.61(m, 12 H), 7.79–8.01(m, 8 H); 13C NMR
(50.32 MHz, CDCl3): d = 27.4, 62.6, 69.0, 70.8, 72.7, 72.9, 93.1,
128.2–130.0, 133.1, 133.2, 133.4, 133.5, 154.3, 165.1, 165.2, 165.6,
166.1; HRMS (MALDI-TOF): m/z = C36H31NO11Na, 676.1795;
Found, 676.1790.
3,4,6-tri-O-Benzoyl-1,2-O-[(2S-(2-tert-butoxycarbonylamino)-
3-methoxy-3-oxopropoxy)phenylmethylene]-a-D-glucopyranoside
(A). [a]2D5 = +3.8 (c = 1.0, CHCl3); 1H NMR (400.13 MHz,
CDCl3): d = 1.41(s, 9 H), 3.60(dd, J = 3.2, 9.9 Hz, 1 H), 3.69((m,
1 H), 3.71(s, 3 H), 4.09(ddd, J = 3.1, 4.9, 7.9 Hz, 1 H), 4.37(dd,
J = 5.0, 11.7 Hz, 2 H), 4.52(dd, J = 2.8, 11.7 Hz, 1 H), 4.74(t, J =
4.2 Hz, 1 H), 5.31(d, J = 8.8 Hz, 1 H), 5.47(d, J = 8.8 Hz, 1 H),
5.73(bs, 1 H), 6.01(d, J = 5.2 Hz, 1 H), 7.21–7.66(m, 12 H), 7.70(d,
J = 7.3 Hz, 2 H), 7.91(d, J = 7.8 Hz, 2 H), 7.94(d, J = 8.2 Hz,
2 H), 8.08(d, J = 7.3 Hz, 2 H); 13C NMR (100.61 MHz, CDCl3):
d = 28.2(3C). 52.5, 53.4, 63.9, 64.2, 67.6, 68.3, 69.0, 72.2, 80.1,
97.6, 121.1, 126.2, 128.2–130.1, 133.0, 133.5, 133.7, 134.5, 155.3,
164.5, 165.1, 166.0, 170.7; HRMS (MALDI-TOF): m/z Calcd for
C43H43NO14+Na, 820.2581; Found, 820.2577.
N -(2,3,4,6-tetra-O-Benzoyl-b-D-glucopyranosyloxycarbonyl)-
1
dodecylamine (10d). [a]2D5 = +34.4 (c = 1.0, CHCl3); H NMR
(200.13 MHz, CDCl3): d = 0.88(t, J = 6.1 Hz, 3 H), 1.15–1.45(m,
20 H), 3.10(ddd, J = 1.4, 6.8, 8.7 Hz, 2 H), 4.30(qd, J = 3.0, 4.1,
7.2 Hz, 1 H), 4.48(dd, J = 4.5, 12.3 Hz, 1 H), 4.65(dd, J = 2.9,
12.4 Hz, 1 H), 4.92(t, J = 5.9 Hz, 1 H), 5.64(dd, J = 8.3, 9.6 Hz,
1 H), 5.75(t, J = 9.6 Hz, 1 H), 5.96(t, J = 9.6 Hz, 1 H), 6.05(d,
J = 8.3 Hz, 1 H), 7.23–7.68(m, 12 H), 7.79–8.08(m, 8 H); 13C
NMR (50.32 MHz, CDCl3): d = 14.1, 22.6, 26.6, 29.1, 29.3, 29.4,
29.4, 29.5, 29.6, 29.6, 31.9, 41.1, 62.7, 69.1, 70.9, 72.8, 72.9, 93.1,
128.2–130.0, 133.1, 133.2, 133.4, 133.4, 153.6, 165.1, 165.2, 165.6,
166.1; HRMS (MALDI-TOF): m/z Calcd for C47H53NO11+Na,
830.3516; Found, 830.3520.
Methyl N-(2,3,4,6-tetra-O-benzoyl-b-D-glucopyranosyloxycar-
1
bonyl)-L-serinate (8). [a]2D5 = +32.9 (c = 1.0, CHCl3); H NMR
N-(2,3,4,6-tetra-O-Benzoyl-b-D-glucopyranosyloxycarbonyl)-2-
(3,4-dimethoxyphenyl)-ethylamine (10e). [a]2D5 = +30.2 (c = 1.0,
CHCl3); 1H NMR (200.13 MHz, CDCl3): d = 2.66(t, J = 7.1 Hz, 2
H), 3.35(ddd, J = 1.5, 6.1, 8.6 Hz, 2 H), 3.79,3.82(2 s, 6 H), 4.31(qd,
J = 2.9, 4.2, 7.9 Hz, 1 H), 4.48(dd, J = 4.6, 12.4 Hz, 1 H), 4.65(dd,
J = 2.9, 12.4 Hz, 1 H), 4.97(t, J = 6.0 Hz, 1 H), 5.62(dd, J = 8.4,
9.6 Hz, 1 H), 5.75(t, J = 9.6 Hz, 1 H), 5.96(t, J = 9.6 Hz, 1 H),
6.05(d, J = 8.4 Hz, 1 H), 6.55–6.74(m, 3 H), 7.23–7.61(m, 12 H),
7.75–8.08(m, 8 H); 13C NMR (50.32 MHz, CDCl3): d = 35.1, 42.3,
55.6, 55.7, 62.6, 69.0, 70.8, 72.7, 72.9, 93.1, 111.2, 111.6, 120.5,
128.2–129.8, 130.7, 133.0, 133.2, 133.4, 133.4, 147.5, 148.8, 153.6,
165.0, 165.1, 165.5, 166.0; HRMS (MALDI-TOF): m/z Calcd for
C45H41NO13+Na, 826.2476; Found, 826.2480.
(400.13 MHz, CDCl3): d 2.44(bs, 1 H), 3.61(s, 3 H), 3.94(ddd,
J = 3.2, 11.4, 14.8 Hz, 2 H), 4.29–4.38(m, 2 H), 4.51(dd, J = 4.8,
12.3 Hz, 1 H), 4.65(dd, J = 2.9, 12.3 Hz, 1 H), 5.68(dd, J = 8.3,
9.5 Hz, 1 H), 5.77(t, J = 9.5 Hz, 1 H), 5.97(m, 2 H), 6.06(d, J =
8.4 Hz, 1 H), 7.25–7.61(m, 12 H), 7.85(d, J = 7.4 Hz, 2 H), 7.91(d,
J = 7.4 Hz, 2 H), 7.96(d, J = 7.4 Hz, 2 H), 8.05(d, J = 7.4 Hz, 2
H); 13C NMR (100.61 MHz, CDCl3): d = 52.6, 56.0, 62.6, 62.6,
68.9, 70.7, 72.8, 73.0, 93.5, 128.3–130.0, 133.2, 133.3, 133.5, 133.5,
153.5, 165.1, 165.2, 165.6, 166.2, 170.2; HRMS (MALDI-TOF):
m/z Calcd for C39H35NO14+Na, 764.1955; Found, 764.1960.
Methyl N-(2,3,4,6-tetra-O-benzoyl-b-D-glucopyranosyloxycar-
bonyl)-L-phenylalaninate (10a). [a]2D5 = +46.5 (c = 1.0, CHCl3);
1H NMR (200.13 MHz, CDCl3): d = 3.07(ddd, J = 5.6, 13.8,
19.4 Hz, 2 H), 3.54(s, 3 H), 4.29(ddd, J = 3.2, 4.5, 7.6 Hz, 1 H),
4.44–4.71(m, 3 H), 5.44(d, J = 8.3 Hz, 1 H), 5.63(dd, J = 8.3, 9.5 Hz,
1 H), 5.74(t, J = 9.5 Hz, 1 H), 5.92(t, J = 9.6 Hz, 1 H), 6.02(d, J =
8.2 Hz, 1 H), 6.98–7.61(m, 17 H), 7.76–8.10(m, 8 H); 13C NMR
(50.32 MHz, CDCl3): d = 37.8, 52.2, 55.0, 62.7, 69.1, 70.6, 72.9,
72.9, 93.3, 127.2, 128.3–130.0, 133.1, 133.3, 133.4, 133.5, 135.2,
153.1, 165.1, 165.1, 165.6, 166.1, 171.0; HRMS (MALDI-TOF):
m/z Calcd for C45H39NO13+Na, 824.2319; Found, 824.2320.
N -(2,3,4,6-tetra-O-Benzoyl-b-D-glucopyranosyloxycarbonyl)-
1
aniline (10f). [a]2D5 = +29.2 (c = 1.0, CHCl3); H NMR (200.13
MHz, CDCl3): d = 4.35(qd, J = 3.1, 4.7, 7.7 Hz, 1 H), 4.50(dd,
J = 4.7, 12.3 Hz, 1 H), 4.65(dd, J = 3.1, 12.3 Hz, 1 H), 5.72(dd,
J = 8.2, 9.6 Hz, 1 H), 5.77(t, J = 9.7 Hz, 1 H), 6.00(t, J =
9.7 Hz, 1 H), 6.12(d, J = 8.2 Hz, 1 H), 6.92–7.20(m, 2 H),
7.23–7.61(m, 16 H), 7.80–8.08(m, 8 H); 13C NMR (50.32 MHz,
CDCl3): d = 62.6, 69.0, 70.8, 72.9, 73.0, 93.2, 118.9, 124.1, 128.2–
130.0, 133.1, 133.3, 133.5, 133.6, 136.8, 150.7, 165.1, 165.3, 165.6,
166.1; HRMS (MALDI-TOF): m/z Calcd for C41H33NO11+Na,
738.1951; Found, 738.1950.
N -(2,3,4,6-tetra-O-Benzoyl-b-D-glucopyranosyloxycarbonyl)-
adamantylamine (10b). [a]2D5 = +34.6 (c = 1.0, CHCl3); 1H NMR
(200.13 MHz, CDCl3): d = 1.61(m, 6 H), 1.82(m, 6 H), 2.01(m, 3
H), 4.26(qd, J = 3.1, 4.7, 8.0 Hz, 1 H), 4.48(dd, J = 4.9, 12.3 Hz,
1 H), 4.62(dd, J = 3.0, 12.3 Hz, 1 H), 4.75(s, 1 H), 5.61(dd, J =
8.6, 9.4 Hz, 1 H), 5.72(t, J = 9.5 Hz, 1 H), 5.88–6.03(m, 2 H),
7.23–7.61(m, 12 H), 7.78–8.08(m, 8 H); 13C NMR (50.32 MHz,
CDCl3): d = 29.3(3C), 36.1(3C), 41.3(3C), 51.2, 62.7, 69.2, 70.9,
72.8, 73.0, 92.6, 128.2–130.0, 133.0, 133.2, 133.4, 133.5, 151.2,
Methyl N -(2,3,4,6-tetra-O-benzoyl-b-D-galactopyranosyloxy-
carbonyl)-L-phenylalaninate (11a). [a]2D5 = +96.6 (c = 1.0, CHCl3);
1H NMR (200.13 MHz, CDCl3): d = 3.10(ddd, J = 5.7, 13.9,
19.6 Hz, 2 H), 3.53(s, 3 H), 4.35–4.78(m, 4 H), 5.46(d, J =
8.2 Hz, 1 H), 5.65(dd, J = 3.3, 10.2 Hz, 1 H), 5.90(dd, J = 8.3,
10.2 Hz, 1 H), 6.01–6.08(m, 2 H), 7.09(m, 2 H), 7.18–7.70(m, 15
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Org. Biomol. Chem., 2011, 9, 5951–5959 | 5957
©

H), 7.73–8.15(m, 8 H); 13C NMR (50.32 MHz, CDCl3): d = 37.7,
52.1, 54.9, 61.7, 67.8, 68.6, 71.7, 72.0, 93.6, 127.2, 128.2–130.0,
133.2, 133.3, 133.3, 133.6, 135.2, 153.1, 165.2, 165.4, 165.4, 165.9,
171.0; HRMS (MALDI-TOF): m/z Calcd for C45H39NO13+Na,
824.2319; Found, 824.2320.
1 H), 5.35(dd, J = 3.3, 10.2 Hz, 1 H), 5.54(t, J = 9.0 Hz, 1 H),
5.72(dd, J = 7.8, 10.2 Hz, 2 H), 5.79–5.95(m, 2 H), 7.06–7.80(m,
21 H), 7.75–8.06(m, 14 H); 13C NMR (50.32 MHz, CDCl3):
d = 29.2(3C), 36.0(3C), 41.3(3C), 51.1, 60.9, 62.2, 67.4, 69.7,
70.8, 71.3, 71.7, 72.9, 73.5, 75.7, 92.5, 101.0, 128.2–130.0, 133.1,
133.2, 133.3, 133.4, 133.5, 133.6, 133.6, 151.1, 164.8, 165.2, 165.2,
165.4, 165.4, 165.5, 165.8; HRMS (MALDI-TOF): m/z Calcd
for C72H65NO19+Na, 1270.4048; Found, 1270.4050.
N-(2,3,4,6-tetra-O-Benzoyl-b-D-galactopyranosyloxycarbonyl)-
adamantylamine (11b). [a]2D5 = +97.3 (c = 1.0, CHCl3); 1H NMR
(200.13 MHz, CDCl3): d = 1.61(m, 6 H), 1.83(m, 6 H), 2.01(m, 3
H), 4.34–4.52(m, 2 H), 4.67(dd, J = 4.2, 8.6 Hz, 1 H), 4.79(s, 1
H), 5.66(dd, J = 3.4, 10.1 Hz, 1 H), 5.87(t, J = 8.3 Hz, 1 H), 5.95–
6.07(m, 2 H), 7.20–7.68(m, 12 H), 7.75–8.16(m, 8 H); 13C NMR
(50.32 MHz, CDCl3): d = 29.2(3C), 36.0(3C), 41.3(3C), 51.2, 61.7,
67.9, 68.9, 71.7, 71.9, 92.9, 128.2–130.0, 133.1, 133.3, 133.4, 133.5,
151.2, 165.3, 165.4, 165.5, 165.9; HRMS (MALDI-TOF): m/z
Calcd for C45H43NO11+Na, 796.2734; Found, 796.2730.
Acknowledgements
AYS, GSK and DP thank fellowship from CSIR-New Delhi.
SH thanks SwanaJayanti Fellowship from DST, New Delhi and
Director-NCL for the LC-MS facility.
Notes and references
Methyl N-(2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyloxycar-
bonyl)- L-phenylalaninate (12a). [a]2D5 = -17.8 (c = 1.0, CHCl3); 1H
NMR (200.13 MHz, CDCl3): d 3.19 (d, J = 5.9 Hz,2 H), 3.75(s, 3
H), 4.45(dd, J = 3.6, 9.7 Hz, 1 H), 4.50(m, 1 H), 4.61–4.82(m, 2 H),
5.60(d, J = 8.3 Hz,1 H), 5.77(dd, J = 2.0, 3.3 Hz, 1 H), 5.89(dd,
J = 3.3, 10.2 Hz, 1 H), 6.10 (t, J = 10.2 Hz, 1 H), 6.29(d, J =
2.0 Hz, 1 H), 7.15–7.63(m, 17 H), 7.80–8.14(m, 8 H); 13C NMR
(50.32 MHz, CDCl3): d = 38.1, 52.4, 54.9, 62.3, 66.1, 69.2, 69.8,
70.5, 91.7, 127.3, 128.2–130.0, 133.0, 133.3, 133.4, 133.6, 135.3,
152.5, 165.1, 165.2, 165.6, 166.0, 171.6; HRMS (MALDI-TOF):
m/z Calcd for C45H39NO13+Na, 824.2319; Found, 824.2320.
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H), 4.34–4.52(m, 2 H), 4.67(dd, J = 4.2, 8.6 Hz,1 H), 4.79(s, 1 H),
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