Expeditious synthesis of β-linked glycosyl serine methylene isosteres (β-C-Gly Ser) via ethynylation of sugar lactones

Article abstract of DOI:10.1055/s-2001-18058

The addition of the lithium derivative of N-Boc 4-ethynyl-2,2-dimethyl-1,3-oxazolidine to tetra-O-benzyl-D-gluco- and galactonolactone and 2-azido-2-deoxy congeners afforded the corresponding ethynyl ketoses in fairly good yields (64-78%). Following the conversion of the ketoses into O-acetates and removal of the acetoxy group by silane reduction, the resulting β-linked ethynyl glycosides were transformed into N-Boc C-glycosyl α-aminobutyric acids by reduction of the triple bond using H₂/Pd(OH)₂ and oxidative cleavage of the oxazolidine ring using the Jones' reagent. After the removal of O-benzyl groups of the carbohydrate moieties by hydrogenation and the reduction of azido to amino group, all compounds were subjected to acetylation and isolated as O- and N-acetyl derivatives. The C-glycosyl α-amino acids prepared correspond to methylene isosteres of O-glycosyl serines.

Full text of DOI:10.1055/s-2001-18058

PAPER
2129
Expeditious Synthesis of -Linked Glycosyl Serine Methylene Isosteres ( -C-
Gly Ser) via Ethynylation of Sugar Lactones
S
ynthesis of -Lin
l
ke
d
G
l
es
s
ne
I
soster
a
e
s
ndro Dondoni,* Giandomenico Mariotti, Alberto Marra, Alessandro Massi
Dipartimento di Chimica, Laboratorio di Chimica Organica, Università di Ferrara, Via Borsari 46, 44100 Ferrara, Italy
E-mail: adn@dns.unife.it
Received 16 July 2001
Since natural O-glycopeptides feature carbohydrate resi-
Abstract: The addition of the lithium derivative of N-Boc 4-ethy-
nyl-2,2-dimethyl-1,3-oxazolidine to tetra-O-benzyl-D-gluco- and
galactonolactone and 2-azido-2-deoxy congeners afforded the cor-
responding ethynyl ketoses in fairly good yields (64–78%). Follow-
dues of various complexity in which the first carbohydrate
moiety is either -D-O-linked3 or -D-O-linked4 to L-
serine (or threonine), both -and -D-C-glycosyl serines
ing the conversion of the ketoses into O-acetates and removal of the incorporating mono-and oligosaccharide moieties are
acetoxy group by silane reduction, the resulting -linked ethynyl
glycosides were transformed into N-Boc C-glycosyl -aminobutyr-
ic acids by reduction of the triple bond using H2/Pd(OH)2 and oxi-
carbon atom of sugars with a good control of the / se-
dative cleavage of the oxazolidine ring using the Jones’ reagent.
After the removal of O-benzyl groups of the carbohydrate moieties
high value artificial amino acids. However, the stereose-
lective installation of an -amino acid chain at the anomer
lectivity is by far a not trivial problem. An additional con-
cern is about the orthogonal protection of the hydroxy
groups of the carbohydrate residue and amino and carbox-
ylate groups of the glycinyl moiety, a prerequisite that
permits the use of these amino acids in solution or solid
phase peptide assembly. While these issues have been
only partially addressed, various synthetic methods lead-
ing to - or -linked C-glycosyl serines based on both lin-
ear and convergent techniques have been reported from
various laboratories including our own.1,5 Worth mention-
ing here are the methods of Dorgan and Jackson,6 Beau
and Skrydstrup,7 and our procedure8 which were especial-
ly designed for the preparation of -linked methylene
isosteres of glycosyl serines via the coupling of homoala-
nine equivalent reagents with anomerically activated gly-
cosyl acceptors. However, in all instances the key C-
glycosidation reaction presented some limitations with re-
spect to / selectivity and/or chemical yield. Hence there
is still a pressing need for synthetic methods leading to
these C-glycosyl amino acids endowed with generality,
simplicity, and high efficiency. We report here on a new
expeditious method for the synthesis of -linked C-glyco-
syl serines employing the ethynyl oxazolidine 1 as a ho-
moalanine equivalent and sugar lactones as glycosyl
donors. While the latter compounds are classical reagents
in carbohydrate chemistry and can be prepared in a multi-
gram scale by oxidation of suitably protected glycopyra-
noses,9 the alkyne 1 has recently become readily available
in an enantiomerically pure form through the efficient
procedure of Villalgordo and co-workers10 involving the
Horner–Wadsworth–Emmons-type ethynylation of D-
serine derived aldehyde (Garner aldehyde),11,12 using di-
methyl 1-diazo-2-oxopropylphosphonate. It has been am-
ply demonstrated that the chiral ethynyl oxazolidine 1 can
be transformed into the corresponding lithium derivative
Li 1 under conditions which do not affect the configura-
tion of the stereocenter of the oxazolidine ring (Scheme 1)
and that the latter reacts readily with carbonyl compounds
while maintaining the same stereochemical integrity. Also
the use of the other partner, the sugar lactones, in this new
by hydrogenation and the reduction of azido to amino group, all
compounds were subjected to acetylation and isolated as O- and N-
acetyl derivatives. The C-glycosyl -amino acids prepared corre-
spond to methylene isosteres of O-glycosyl serines.
Key words: alkynyl glycosides, glycopeptides, C-glycosides, C-
glycosyl amino acids
Among the various types of glycosyl amino acids featur-
ing an unnatural anomeric carbon linkage between the
carbohydrate and the glycinyl moiety, CH(NH2)CO2H (C-
glycosyl amino acids), the - and -linked C-glycosyl
serines shown in the Figure (X = CH2) are in the forefront
of current synthetic work in this field of research.1 These
compounds as methylene isosteres of O-glycosyl serines
(X = O), the main constituents of naturally occurring O-
glycopeptides and proteins, are precious tools in studies of
glycobiology directed toward a better understanding at
molecular level of the primary role exerted by glycans in
glycopeptide biological activity.2 Moreover, given the ex-
pected higher resistance of the C-glycosidic bond with re-
spect to the O-glycosidic linkage toward the chemical and
enzymatic degradation, the C-glycosyl serines can be used
for the preparation of glycosidase inhibitors and lead com-
pounds for drug discovery.
OR
OR
NHBoc
CO2H
O
O
X
(RO)n
(RO)n
NHBoc
CO2H
X
α-D-Gly Ser
β-D-Gly Ser
Figure Natural -and -linked O-glycosyl serines (X = O) and their
unnatural methylene isosteres (X = CH2). One or more OR groups re-
present mono- or oligosaccharide residues.
Synthesis 2001, No. 14, 26 10 2001. Article Identifier:
1437-210X,E;2001,0,14,2129,2137,ftx,en;E14701SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

2130
A. Dondoni et al.
PAPER
convergent approach to -D-linked C-glycosyl serines re- to organometallic reagent due to the high affinity of ceri-
lied on earlier reactions of these compounds with various um for oxygen and nitrogen atoms. Attempts to reduce the
organometallic reagents including metalated acetylides13 mixture of ketoses 4 under the standard anomeric deoxy-
to give ketoses which were deoxygenated selectively to - genation conditions13a using Et3SiH, BF3 OEt2 in CH2Cl2
C-glycosides.
at –10 °C induced mainly the cleavage of the acid-sensi-
tive oxazolidine ring, the key moiety of the side chain
which was devoted to serve as the glycinyl group equiva-
lent. However, the almost quantitative conversion of 4
into the mixture of ketose acetates 6 and treatment at –40
°C with the Et3SiH, TMSOTf (0.5 equiv) reducing sys-
tem, which was successfully employed in an earlier work
in our laboratory,9,14 resulted in the formation of the -
linked C-galactosyl alkyne 8 in a rewarding 82% isolated
yield. These milder reaction conditions were compatible
with the integrity of the oxazolidine ring. Nevertheless the
structure of this compound with particular regard to the
configuration of the stereocenter of the oxazolidine ring
was confirmed by transformation into the C-galactosyl al-
kane 14 via diimide reduction of the triple bond
(Scheme 3) and comparison with the same product pre-
pared by another route.8 Next, the elaboration of the
alkyne side-chain of 8 was carried out by two sequential
high yield steps. First of all, the hydrogenation over
Pd(OH)2 reduced the triple bond and at the same time re-
NBoc
NBoc
O
O
BuLi
THF, -30 °C
Li
.
1
Li 1
Scheme 1
A model reaction was generated by addition of a slight ex-
cess (1.3 equiv) of the lithium acetylide Li 1 generated in
situ as shown in Scheme 1 to the tetra-O-benzyl-D-galac-
tonolactone 2 in THF at –30 °C. (Scheme 2). The reaction
afforded a mixture of diastereomeric galactose oxazolidi-
nylacetylenes 4 in 64% isolated yield. The use of the ceri-
um derivative of 1 (2 equiv) as reported in other addition
reactions of alkynes to sugar lactones,13b resulted in the
formation of 4 in much lower yield (ca. 20%). Very likely
this is due to the presence of the N-Boc group which binds
BocN
R1 OBn
O
R1 OBn
.
O
R2
R2
Li 1
O
BnO
BnO
OH
BnO
O
THF, -30 °C
64-73%
BnO
2, 3
4, 5
BocN
R1 OBn
O
O
R2
BnO
Ac2O, Et3N
Et3SiH, TMSOTf
BnO
CH2Cl2, r. t.
90-96%
CH2Cl2, -40 °C
82-87%
OAc
6, 7
BocN
O
R1 OAc
R1 OBn
1. H2, Pd(OH)2
2. Ac2O, Py
BocN
O
O
R2
AcO
R2
O
BnO
BnO
AcO
90-91%
10, 11
8, 9
R1 OAc
O
NHBoc
CO2H
R2
Jones
AcO
AcO
acetone, 0 °C to r. t.
90%
12, 13
Scheme 2 Galacto series: for 2, 4, 6, 8 R1 = OBn, R2 = H; for 10 and 12 R1 = OAc, R2 = H. Gluco series: for 3, 5, 7, 9 R1 = H, R2 = OBn; for
11 and 13 R1 = H, R2 = OAc
Synthesis 2001, No. 14, 2129–2137 ISSN 0039-7881 © Thieme Stuttgart · New York

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Synthesis of -Linked Glycosyl Serine Methylene Isoesters
2131
BocN
O
BnO
BnO
OBn
O
BnO
BnO
OBn
O
TsNHNH2
AcONa
BocN
O
BnO
BnO
DME-H2O
85%
14
8
Scheme 3
moved the O-benzyl protective groups. The acetylation of groups. In both cases the acetylation of the resulting reac-
the resulting crude C-alkyl glycoside afforded the tetra-O- tion mixtures afforded the peracetylated C-glycosides 23
acetyl derivative 10 (90% yield). Then this compound was and 24, which upon treatment with the Jones’ reagent
subjected to the oxidative cleavage of the N-Boc oxazoli- were transformed into the final products 25 and 26. On the
dine ring using the Jones’ reagent (CrO3, H2SO4, H2O) to basis of the above observations (see Scheme 3) and the lit-
give in a single step8,15 the -D-galactosyl -aminobutyric erature precedents,15 it was reasonably assumed that the
acid 12, the galactosyl serine methylene isostere ( -D-C- integrity of the stereocenter bearing the nitrogen atom re-
Gal Ser) according to the structures shown in Figure 1. mained intact throughout the whole reaction sequence and
The same reaction sequence was followed for the synthe- therefore the original (S)-configuration of 1 was also as-
sis of the -linked glucosyl serine methylene isostere ( - signed to the glycinyl moiety of the amino acids 25 and
D-C-Glc Ser, 13) by initial coupling of D-gluconolactone 26. As a confirmation of this assumption, the methyl ester
3 with lithium ethynyloxazolidine Li 1. Yields of each of 26 appeared to be identical based on the optical rotation
steps and stereoselectivity in the crucial reductive step of value to the same product recently prepared by Fuchss and
the alkynyl ketose acetate 7 were comparable to those reg- Schmidt by another route.18
istered in the galacto series.
In conclusion, a new synthetic route has been described
As an expanded scope of the methodology we considered leading to -D-linked methylene isosteres of glycosyl
the synthesis of the 2-acetamido-2-deoxy derivatives of serines starting from readily available sugar lactones. The
the above C-glucosyl and C-galactosyl serines. Although methodology involves a sequence of simple and efficient
in the high percentages of naturally occurring O-glu- reactions and appears to be of general application for the
copeptides of cell surfaces, serine (or threonine) residues synthesis of compounds containing totally hydroxylated
are -D-O-linked to N-acetylgalactosamine (GalNAc) or sugar residues or their 2-acetamido-2-deoxy derivatives.
N-acetylglucosamine (GlcNAc),16 -D-O-linkages be- Owing to the orthogonal protection of their functional
tween the same amino acid and sugar residues have been groups, the C-glycosil amino acids prepared are suitably
observed in nuclear and cytoplasmatic proteins.17 Hence tailored for their use as building blocks in glycopeptide
the synthesis of analogue glycosyl amino acids with -C- assembly by both N-Boc and N-Fmoc techniques. To this
linkages is undoubtedly of great interest.18 The various aim, the preparation of the N-Fmoc protected derivatives
steps leading to the 2-acetamido-2-deoxy galactosyl 28 is illustrated in Scheme 5. This compound was synthe-
serine methylene isostere ( -D-C-GalNAc Ser, 25) and the sized by elaboration of the oxazolidine ring of 10, the
glucosyl derivative ( -D-C-GlcNAc Ser, 26) starting from same intermediate leading to the N-Boc derivative 12 (see
the corresponding 2-azido-2-deoxygalacto- and glucono- Scheme 2), by hydrolysis, N-protection and oxidation in
lactones 15 and 16 are shown in Scheme 4. While the ini- 76% overall yield.
tial step involving the addition of Li 1 to the lactones
occurred smoothly to give the ketoses 17 and 18 in similar
good yields to those registered in Scheme 2, the deoxy-
All moisture-sensitive reactions were performed under N2 using
oven-dried glassware. Anhyd solvents were dried over standard
genation of the ketose acetates 19 and 20 to the C-alkynyl
glycosides 21 and 22 presented some problems. For this
reaction to proceed, an excess of Lewis acid promoter
(TMSOTf) was required, however, under these conditions
the oxazolidine ring could not longer survive. After some
experimentation we found that the use of 2.5–3.0 equiva-
lents of TMSOTf and 10 equivalents of Et3SiH at –40 °C
in CH2Cl2 reduced 19 and 20 to 21 and 22, respectively, in
35–43% yield while ca. 30% of the unaltered ketose ace-
tates were recovered. Finally, the hydrogenation of 21 and
22 was a quite productive operation since it reduced in one
step the triple bond to single bond, the azido group to the
amino group, and removed the O-benzyl protective
drying agents19 and freshly distilled prior to use. Commercially
available powdered 4Å molecular sieves (5 m average particle
size) were used without further activation. Reactions were moni-
tored by TLC on silica gel 60 F254 with detection by charring with
H2SO4 and/or ninhydrin. Flash column chromatography20 was per-
formed on silica gel 60 (230–400 mesh). Melting points were deter-
mined with a capillary apparatus. Optical rotations were measured
at 20 2 °C in the stated solvent; [ ]D values are given in 10–1 deg
cm2 g–1. 1H NMR (300 MHz) spectra were recorded for CDCl3 so-
lutions at r.t. unless otherwise specified: Chemical shifts are in ppm
( ) from TMS as internal standard; assignments were aided by ho-
mo- and heteronuclear two dimensional experiments. MALDI-TOF
mass spectra were acquired using -cyano-4-hydroxycinnamic acid
as the matrix.
Synthesis 2001, No. 14, 2129–2137 ISSN 0039-7881 © Thieme Stuttgart · New York

2132
A. Dondoni et al.
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BocN
R1 OBn
O
R1 OBn
O
O
.
R2
BnO
R2
BnO
Li 1
O
THF, -30 °C
70-78%
N3
N3
OH
15, 16
17, 18
BocN
R1 OBn
O
O
R2
BnO
Ac2O, Et3N
Et3SiH, TMSOTf
N3
CH2Cl2, r. t.
90%
CH2Cl2, -40 °C
35-43%
OAc
19, 20
BocN
O
R1 OAc
R1 OBn
1. H2, Pd(OH)2
BocN
O
O
R2
AcO
R2
O
2. Ac2O, Py
BnO
N3
AcHN
85-87%
23, 24
21, 22
R1 OAc
O
NHBoc
CO2H
R2
AcO
Jones
AcHN
acetone, 0 °C to r. t.
71-75%
25, 26
Scheme 4 Galacto series: for 15, 17, 19, 21 R1 = OBn, R2 = H; for 23 and 25 R1 = OAc, R2 = H. Gluco series: for 16, 18, 20, 22 R1 = H,
R2 = OBn; for 24 and 26 R1 = H, R2 = OAc
AcO
AcO
OAc
AcO
AcO
OAc
1. TFA
BocN
NHFmoc
OH
O
O
O
2. FmocOSu
AcO
AcO
80%
27
10
AcO
AcO
OAc
NHFmoc
CO2H
O
Jones
AcO
acetone, 0 °C to r. t.
95%
28
Scheme 5
6,7,8,10-Tetra-O-benzyl-2,3,4-trideoxy-1,2-N,O-isopropyli-
dene-2-(tert-butoxycarbonylamino)-D-glycero-L-gluco-deco-
pyran-3-yn-5-ulose (4); Typical Procedure
To a cooled (–30 °C) and stirred solution of 1 (0.60 g, 2.67 mmol)
in anhyd THF (11 mL) was slowly added BuLi (1.6 mL, 2.6 mmol,
of a 1.6 M solution in hexane) and the stirring was continued at –30
°C for an additional 30 min. To this mixture was added dropwise a
solution of the lactone 2 (1.10 g, 2.04 mmol) in anhyd THF (5 mL).
The mixture was stirred at –30 °C for 1.5 h, treated with 1 M phos-
phate buffer at pH 7 (5 mL) and allowed to reach r.t. The suspension
was diluted with Et2O (20 mL) and the phases were separated. The
aqueous layer was extracted twice with Et2O (20 mL), the combined
organic layers were dried (Na2SO4) and concentrated. The residue
was eluted from a column of silica gel with cyclohexane–EtOAc
(from 9:1 to 3:1) to afford first the unreacted 1 (0.25 g, 42%). The
second fraction eluted was the syrupy 4 as a 1:1 mixture of anomers
(1.00 g, 64%).
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Synthesis of -Linked Glycosyl Serine Methylene Isoesters
2133
1H NMR (DMSO-d6 + D2O, 100 °C): (selected data) = 7.40–7.18
(m, 20 H, 4 C6H5), 5.58 (d, 0.5 H, J = 10.0 Hz, PhCH2), 5.44 (d, 0.5
H, J = 9.0 Hz, PhCH2), 4.86–4.62 (m, 8 H), 4.52–4.32 (m, 3 H),
4.06 (ddd, 0.5 H, J 8,9 = 1.0, J9,10a = 6.0, J9,10b = 6.0 Hz, H-9 ), 3.98
(dd, 0.5 H, J7,8 = 3.0 Hz, H-8 ), 3.94 (dd, 0.5 H, J7,8 = 4.0, J8,9 = 1.0
Hz, H-8 ), 3.89 (d, 0.5 H, J6,7 = 10.0 Hz, H-6 ), 3.86 (dd, 0.5 H, H-
7 ), 3.80 (dd, 0.5 H, J9,10a = 3.0, J9,10b = 3.0 Hz, H-9 ), 3.72 (d, 0.5
H, J6,7 = 10.0 Hz, H-6 ), 3.63–3.44 (m, 2 H, 2 H-10), 1.41 (br s, 15
H).
5-O-Acetyl-6,7,8,10-tetra-O-benzyl-2,3,4-trideoxy-1,2-N,O-
isopropylidene-2-(tert-butoxycarbonylamino)-D-glycero-L-
gluco-decopyran-3-yn-5-ulose (6); Typical Procedure
A solution of 4 (652 mg, 0.82 mmol), Et3N (1.18 mL, 8.50 mmol),
and Ac2O (0.81 mL, 8.50 mmol) in anhyd CH2Cl2 (4 mL) was kept
at r.t. for 12 h, and then concentrated. The residue was eluted from
a column of silica gel with 4:1 cyclohexane–EtOAc to afford the
syrupy 6 (637 mg, 96%) as a 1:1 mixture of anomers.
1H NMR (DMSO-d6, 140 °C): ( -anomer) = 7.38–7.24 (m, 20 H,
4 C6H5), 4.85 and 4.79 (2 d, 2 H, J = 11.4 Hz, PhCH2), 4.85 and 4.57
(2 d, 2 H, J = 11.5 Hz, PhCH2), 4.75 and 4.71 (2 d, 2 H, J = 11.5 Hz,
PhCH2), 4.68 (dd, 1 H, J1a,2 = 6.0, J1b,2 = 2.0 Hz, H-2), 4.56 and 4.48
(2 d, 2 H, J = 11.5 Hz, PhCH2), 4.14 (ddd, 1 H, J8,9 = 1.0,
MALDI-TOF MS: m/z = 787.5 (M+ + Na), 803.7 (M+ + K).
Anal. Calcd for C46H53NO9: C, 72.32; H, 6.99; N, 1.83. Found:C,
72.39; H, 7.05; N, 1.96.
J
9,10a = 6.0, J9,10b = 6.0 Hz, H-9), 4.09 (dd, 1 H, J1a,1b = 8.5 Hz, H-
6,7,8,10-Tetra-O-benzyl-2,3,4-trideoxy-1,2-N,O-isopropyli-
dene-2-(tert-butoxycarbonylamino)-D-glycero-D-ido-deco-
pyran-3-yn-5-ulose (5)
Treatment of 3 (538 mg, 1.00 mmol) with 1 (300 mg, 1.30 mmol)
as described for the preparation of 4 gave, after column chromatog-
raphy on silica gel (6:1 cyclohexane–EtOAc), the syrupy 5 (560 mg,
73%) as a 7:3 mixture of anomers.
1H NMR (DMSO-d6, 120 °C): (selected data) = 7.40–7.18 (m, 20
H, 4 C6H5), 5.65 (d, 0.7 H, J = 11.0 Hz, PhCH2 ), 4.86–4.62 (m, 8
H), 4.52–4.32 (m, 4 H), 3.72 (d, 0.7 H, J6,7 = 9.5 Hz, H-6 ), 3.61–
3.44 (m, 2 H, 2 H-10).
1a), 4.04 (dd, 1 H, J7,8 = 3.0 Hz, H-8), 3.99 (d, 1 H, J6,7 = 9.5 Hz, H-
6), 3.90 (dd, 1 H, H-1b), 3.84 (dd, 1 H, H-7), 3.69 (dd, 1 H,
J10a,10b = 10.0 Hz, H-10a), 3.56 (dd, 1 H, H-10b), 1.99 (s, 3 H,
CH3CO), 1.56 and 1.45 (2 s, 6 H, 2 CH3), 1.42 (s, 9 H, t-C4H9).
1H NMR (DMSO-d6, 140 °C): ( -anomer) = 7.38–7.22 (m, 20 H,
4 C6H5), 4.97 and 4.85 (2 d, 2 H, J = 11.0 Hz, PhCH2), 4.81 and 4.58
(2 d, 2 H, J = 11.5 Hz, PhCH2), 4.77 and 4.70 (2 d, 2 H, J = 11.8 Hz,
PhCH2), 4.61 (dd, 1 H, J1a,2 = 6.0, J1b,2 = 2.8 Hz, H-2), 4.54 and 4.46
(2 d, 2 H, J = 12.0 Hz, PhCH2), 4.11 (dd, 1 H, J7,8 = 2.8, J8,9 = 1.3
Hz, H-8), 4.04 (dd, 1 H, J1a,1b = 8.8 Hz, H-1a), 4.01 (d, 1 H,
J
6,7 = 10.0 Hz, H-6), 3.94 (dd,1 H, H-7), 3.92 (ddd, 1 H, J9,10a = 6.0,
J9,10b = 5.5 Hz, H-9), 3.86 (dd, 1 H, H-1b), 3.67 (dd, 1 H,
10a,10b = 10.2 Hz, H-10a), 3.54 (dd, 1 H, H-10b), 2.09 (s, 3 H,
MALDI-TOF MS: m/z = 786.9 (M+ + Na), 802.7 (M+ + K).
J
Anal. Calcd for C46H53NO9: C, 72.32; H, 6.99; N, 1.83. Found: C,
72.35; H, 7.10; N, 1.83.
CH3CO),1.52 and 1.43 (2 s, 6 H, 2 CH3), 1.43 (s, 9 H, t-C4H9).
MALDI-TOFMS: m/z = 829.1 (M+ + Na), 845.0 (M+ + K).
6-Azido-7,8,10-tri-O-benzyl-2,3,4,6-tetradeoxy-1,2-N,O-iso-
propylidene-2-(tert-butoxycarbonylamino)-D-glycero-L-gluco-
decopyran-3-yn-5-ulose (17)
Anal. Calcd for C48H55NO10: C, 71.53; H, 6.88; N, 1.73. Found: C,
71.75; H, 6.83; N, 1.60.
Treatment of 15 (1.70 g, 3.60 mmol) with 1 (1.06 g, 4.70 mmol) as
described for the preparation of 4 gave, after column chromatogra-
phy on silica gel with 5:1 cyclohexane–EtOAc, the syrupy 17 (1.85
g, 78%) as a 1.5:1 mixture of anomers.
1H NMR (DMSO-d6 + D2O, 120 °C): (selected data) = 7.41–7.22
(m, 15 H, 3 C6H5), 4.80–4.45 (m, 7 H), 4.10–4.02 (m, 3 H), 3.91 (dd,
0.6 H, J7,8 = 3.0, J8,9 = 1.0 Hz, H-8 ), 3.89 (dd, 0.4 H, J7,8 = 2.5,
5-O-Acetyl-6,7,8,10-tetra-O-benzyl-2,3,4-trideoxy-1,2-N,O-
isopropylidene-2-(tert-butoxycarbonylamino)-D-glycero-D-ido-
decopyran-3-yn-5-ulose (7)
Ketose 5 (547 mg, 0.72 mmol) was acetylated as described for the
preparation of 6. The crude product was eluted from a column of sil-
ica gel with 5:1 cyclohexane–EtOAc to afford the syrupy 7 (518 mg,
90%) as a 3:1 mixture of anomers.
1H NMR (DMSO-d6, 120 °C): ( anomer) = 7.40–7.21 (m, 20 H,
4 C6H5), 4.89 and 4.79 (2 d, 2 H, J = 12.0 Hz, PhCH2), 4.81 and 4.70
(2 d, 2 H, J = 11.0 Hz, PhCH2), 4.75 and 4.59 (2 d, 2 H, J = 11.5 Hz,
PhCH2), 4.71 (dd, 1 H, J1a,2 = 6.0, J1b,2 = 2.0 Hz, H-2), 4.53 (s, 2 H,
PhCH2), 4.09 (dd, 1 H, J1a,1b = 8.5 Hz, H-1a), 3.98 (ddd, 1 H,
J8,9 = 10.0, J9,10a = 3.5, J9,10b = 7.0 Hz, H-9), 3.92 (dd, 1 H, H-1b),
3.84 (dd, 1 H, J6,7 = 9.0, J7,8 = 8.5 Hz, H-7), 3.72–3.63 (m, 3 H, H-
6, 2 H-10), 3.60 (dd, 1 H, H-8), 2.00 (s, 3 H, CH3CO), 1.58 and 1.48
(2 s, 6 H, 2 CH3),1.42 (s, 9 H, t-C4H9).
1H NMR (DMSO-d6, 120 °C): ( anomer) = 7.40–7.22 (m, 20 H,
4 C6H5), 5.05 and 4.59 (2 d, 2 H, J = 11.5 Hz, PhCH2), 4.81 and 4.75
(2 d, 2 H, J = 12.0 Hz, PhCH2), 4.79 and 4.75 (2 d, 2 H, J = 11.5 Hz,
PhCH2), 4.65 (dd, 1 H, J1a,2 = 6.0, J1b,2 = 2.5 Hz, H-2), 4.57 and 4.51
(2 d, 2 H, J = 11.5 Hz, PhCH2), 4.06 (dd, 1 H, J1a,1b = 9.0 Hz, H-1a),
3.88 (dd, 1 H, H-1b), 3.72–3.63 (m, 6 H), 2.15 (s, 3 H, CH3CO),
1.52 and 1.22 (2 s, 6 H, 2 CH3), 1.20 (s, 9 H, t-C4H9).
J8,9 = 0.5 Hz, H-8 ), 3.72–3.50 (m, 3 H), 1.58 and 1.47 (2 s, 3.6 H,
2
CH3), 1.55 and 1.44 (2 s, 2.4 H, 2 CH3), 1.46 (s, 5.4 H, t-
C4H9), 1.43 (s, 3.6 H, t-C4H9).
MALDI-TOF MS: m/z = 721.8 (M+ + Na), 737.6 (M+ + K).
Anal. Calcd for C39H46N4O8: C, 67.03; H, 6.64; N, 8.02. Found: C,
66.98; H, 6.70; N, 8.09.
6-Azido-7,8,10-tri-O-benzyl-2,3,4,6-tetradeoxy-1,2-N,O-iso-
propylidene-2-(tert-butoxycarbonylamino)-D-glycero-D-ido-
decopyran-3-yn-5-ulose (18)
Treatment of 16 (1.00 g, 2.11 mmol) with 1 (0.61 g, 2.71 mmol) as
described for the preparation of 4 gave, after column chromatogra-
phy on silica gel (4:1 cyclohexane–EtOAc), the syrupy 18 (1.00 g,
70%) as a 1.5:1 mixture of anomers.
1H NMR (DMSO-d6, 120 °C): (selected data) = 7.35–7.21 (m, 15
H, 3 C6H5), 4.83 (dd, 0.6 H, J1a,2 = 6.0, J1b,2 = 2.5 Hz, H-2 ), 4.79
and 4.52 (2 d, 1.2 H, J = 11.5 Hz, PhCH2), 4.64 and 4.54 (2 d, 2 H,
MALDI-TOF MS: m/z = 828.9 (M+ + Na), 845.3 (M+ + K).
J = 11.4 Hz, PhCH2), 4.74–4.45 (m, 5 H), 4.14 (dd, 0.6 H, J1a,1b
=
Anal. Calcd for C48H55NO10: C, 71.53; H, 6.88; N, 1.73. Found: C,
71.55; H, 6.80; N, 1.70.
10.0 Hz, H-1a ), 4.09 (dd, 0.6 H, H-1b ), 4.09–4.06 (m, 0.8 H),
4.02–3.90 (m, 3 H), 3.72–3.58 (m, 3 H), 1.62 and 1.54 (2 s, 3.6 H,
2
CH3), 1.60 and 1.53 (2 s, 2.4 H, 2 CH3), 1.45 (s, 5.4 H, t-
5-O-Acetyl-6-azido-7,8,10-tri-O-benzyl-2,3,4,6-tetradeoxy-1,2-
N,O-isopropylidene-2-(tert-butoxycarbonylamino)-D-glycero-L-
gluco-decopyran-3-yn-5-ulose (19); Typical Procedure
C4H9), 1.43 (s, 3.6 H, t-C4H9).
MALDI-TOF MS: m/z = 721.3 (M+ + Na), 737.6 (M+ + K).
A solution of 17 (256 mg, 0.37 mmol) and 4-(dimethylamino)pyri-
dine (10 mg) in Ac2O (3 mL) and pyridine (3 mL) was kept at r.t.
Anal. Calcd for C39H46N4O8: C, 67.03; H, 6.64; N, 8.02. Found: C,
67.10; H, 6.64; N, 7.95.
Synthesis 2001, No. 14, 2129–2137 ISSN 0039-7881 © Thieme Stuttgart · New York

2134
A. Dondoni et al.
PAPER
5,9-Anhydro-6,7,8,10-tetra-O-benzyl-2,3,4-trideoxy-1,2-N,O-
isopropylidene-2-(tert-butoxycarbonylamino)-D-erythro-L-
galacto-dec-3-ynitol (9)
for 30 min and then concentrated. The crude product was eluted
from a column of silica gel with 5:1 cyclohexane–EtOAc to afford
the syrupy 19 (244 mg, 90%) as a 7:3 mixture of anomers.
Treatment of 7 (510 mg, 0.63 mmol) as described for the prepara-
tion of 8 gave, after column chromatography on silica gel (5:1 cy-
clohexane–EtOAc), 9 (410 mg, 87%) as a white solid; mp 95–96 °C
(MeOH); [ ]D +63.0 (c = 1, CHCl3).
1H NMR (DMSO-d6, 100 °C): ( anomer) = 7.42–7.25 (m, 15 H,
3 C6H5), 4.82 and 4.67 (2 d, 2 H, J = 11.5 Hz, PhCH2), 4.80 and 4.56
(2 d, 2 H, J = 11.5 Hz, PhCH2), 4.69 (dd, 1 H, J1a,2 = 6.0, J1b,2 = 2.0
Hz, H-2), 4.55 and 4.47 (2 d, 2 H, J = 12.0 Hz, PhCH2), 4.14 (ddd,
1 H, J8,9 = 0.5, J9,10a = 6.3, J9,10b = 6.0 Hz, H-9), 4.11 (dd, 1 H,
1H NMR (DMSO-d6, 120 °C): = 7.38–7.19 (m, 20 H, 4 C6H5),
4.99 and 4.74 (2 d, 2 H, J = 11.0 Hz, PhCH2), 4.82 and 4.75 (2 d, 2
H, J = 11.5 Hz, PhCH2), 4.73 and 4.58 (2 d, 2 H, J = 11.0 Hz,
PhCH2), 4.67 (ddd, 1 H, J1a,2 = 6.5, J1b,2 = 2.5, J2,5 = 1.5 Hz, H-2),
4.56 and 4.51 (2 d, 2 H, J = 11.8 Hz, PhCH2), 4.18 (dd, 1 H,
J5,6 = 9.5 Hz, H-5), 4.07 (dd, 1 H, J1a,1b = 8.5 Hz, H-1a), 3.89 (dd, 1
H, H-1b), 3.74–3.61 (m, 2 H, 2 H-10), 3.68 (dd, 1 H, J6,7 = 10.0 Hz,
H-6), 3.57–3.53 (m, 1 H, H-9), 3.49 (dd, 1 H, J7,8 = 9.0, J8,9 = 8.0
Hz, H-8), 3.48 (dd, 1 H, H-7), 1.52 and 1.42 (2 s, 6 H, 2 CH3), 1.42
(s, 9 H, t-C4H9).
J7,8 = 2.8 Hz, H-8), 4.09 (dd, 1 H, J1a,1b = 8.5 Hz, H-1a), 3.97 (d, 1
H, J6,7 = 10.5 Hz, H-6), 3.93 (dd, 1 H, H-1b), 3.79 (dd, 1 H, H-7),
3.68 (dd,1 H, J10a,10b = 10.0 Hz, H-10a), 3.56 (dd, 1 H, H-10b), 2.07
(s, 3 H, CH3CO), 1.57 and 1.47 (2 s, 6 H, 2 CH3), 1.46 (s, 9 H, t-
C4H9).
MALDI-TOF MS: m/z = 763.6 (M+ + Na), 779.9 (M+ + K).
Anal. Calcd for C41H48N4O9: C, 66.47; H, 6.53; N, 7.56. Found: C,
66.40; H, 6.60; N, 7.51.
MALDI-TOF MS: m/z = 770.9 (M+ + Na), 787.0 (M+ + K).
5-O-Acetyl-6-azido-7,8,10-tri-O-benzyl-2,3,4,6-tetradeoxy-1,2-
N,O-isopropylidene-2-(tert-butoxycarbonylamino)-D-glycero-D-
ido-decopyran-3-yn-5-ulose (20)
Anal. Calcd for C46H53NO8: C, 73.87; H, 7.14; N, 1.87. Found: C,
73.91; H, 7.08; N, 1.97.
Ketose 18 (174 mg, 0.25 mmol) was acetylated as described for the
preparation of 19. The crude product was eluted from a column of
silica gel with 4:1 cyclohexane–EtOAc to afford syrupy 20 (166
mg, 90%) as a 3:1 mixture of anomers.
5,9-Anhydro-6-azido-7,8,10-tri-O-benzyl-2,3,4,6-tetradeoxy-
1,2-N,O-isopropylidene-2-(tert-butoxycarbonylamino)-D-threo-
L-galacto-dec-3-ynitol (21)
Treatment of 19 (549 mg, 0.74 mmol) as described for the prepara-
tion of 8 gave, after column chromatography on silica gel (5:1 cy-
clohexane–EtOAc), first 21 (216 mg, 43%) as a syrup; [ ]D +66.7
(c = 0.5, CHCl3).
1H NMR (DMSO-d6, 100 °C): = 7.42–7.23 (m, 15 H, 3 C6H5),
4.81 and 4.67 (2d, 2 H, J = 12.0 Hz, PhCH2), 4.79 and 4.54 (2 d, 2
H, J = 11.5 Hz, PhCH2), 4.63 (ddd, 1 H, J1a,2 = 6.3, J1b,2 = 2.5, J2-
5 = 1.0 Hz, H-2), 4.51 and 4.46 (2 d, 2 H, J = 12.0 Hz, PhCH2), 4.05
(dd, 1 H, J1a,1b = 8.8 Hz, H-1a), 4.04 (dd, 1 H, J7,8 = J8,9 = 2.0 Hz, H-
8), 4.03 (dd, 1 H, J6,7 = 9.0 Hz, H-7), 3.91 (dd, 1 H, H-1b), 3.75
(ddd, 1 H, J9,10a = 5.5, J9,10b = 6.0 Hz, H-9), 3.66–3.62 (m, 2 H), 3.58
(dd, 1 H, J10a,10b = 10.0 Hz, H-10a), 3.54 (dd, 1 H, H-10b), 1.52 (s,
3 H, CH3),1.43 (s, 12 H, CH3, t-C4H9).
1H NMR(DMSO-d6, 120 °C):
( anomer) = 7.38–7.21 (m, 15 H,
3 C6H5), 4.79 (s, 2 H, PhCH2), 4.75 and 4.61 (2 d, 2 H, J = 11.4 Hz,
PhCH2), 4.71 (dd, 1 H, J1a,2 = 2.0, J1b,2 = 6.0 Hz, H-2), 4.56 and 4.51
(2 d, 2 H, J = 12.0 Hz, PhCH2), 4.11 (dd, 1 H, J1a,1b = 8.8 Hz, H-1a),
3.94 (dd, 1 H, H-1b), 3.86 (d, 1 H, J6,7 = 9.5 Hz, H-6), 3.78–3.66 (m,
5 H), 2.10 (s, 3 H, CH3CO), 1.45 and 1.42 (2 s, 6 H, 2 CH3), 1.41 (s,
9 H, t-C4H9).
MALDI-TOF MS: m/z = 763.7 (M+ + Na), 779.7 (M+ + K).
Anal. Calcd for C41H48N4O9: C, 66.47; H, 6.53; N, 7.56. Found: C,
66.50; H, 6.58; N, 7.50.
5,9-Anhydro-6,7,8,10-tetra-O-benzyl-2,3,4-trideoxy-1,2-N,O-
isopropylidene-2-(tert-butoxycarbonylamino)-D-threo-L-
galacto-dec-3-ynitol (8); Typical Procedure
MALDI-TOF MS: m/z = 706.2 (M+ + Na), 722.4 (M+ + K).
A mixture of the acetate 6 (400 mg, 0.49 mmol), activated 4Å pow-
dered molecular sieves (0.80 g), and anhyd CH2Cl2 (5 mL) was
stirred at r.t. for 15 min, then cooled to –40 °C. To the mixture was
added Et3SiH (782 L, 4.9 mmol) and then TMSOTf (44 L, 0.25
mmol). Stirring was continued at –40 °C for an additional 2 h, then
the mixture was diluted with Et3N (70 L, 0.5 mmol), filtered
through Celite, and concentrated. The residue was eluted from a
column of silica gel with 5:1 cyclohexane–EtOAc to afford 8 (300
mg, 82%) as a white solid; mp 111–113 °C (pentane); [ ]D +50.5 (c
= 1.5, CHCl3).
1H NMR (DMSO-d6, 120 °C): = 7.41–7.23 (m, 20 H, 4 C6H5),
4.90 and 4.78 (2 d, 2 H, J = 11.0 Hz, PhCH2), 4.83 and 4.55 (2 d, 2
H, J = 11.5 Hz, PhCH2), 4.76 and 4.63 (2 d, 2 H, J = 12.0 Hz,
PhCH2), 4.63 (ddd, 1 H, J1a,2 = 2.0, J1b,2 = 3.0, J2,5 = 1.5 Hz, H-2),
4.53 and 4.47 (2 d, 2 H, J = 12.0 Hz, PhCH2), 4.09 (dd, 1 H, J
5,6 = 9.0 Hz, H-5), 4.07 (dd, 1 H, J1a,1b = 8.5 Hz, H-1a), 4.01 (dd, 1
H, J7,8 = 3.0, J8,9 = 1.0 Hz, H-8), 3.88 (dd, 1 H, H-1b), 3.76 (dd, 1 H,
Anal. Calcd for C39H46N4O7: C, 68.60; H, 6.79; N, 8.21. Found: C,
68.72; H, 6.70; N, 8.10.
Unreacted 19 was eluted out as the second fraction (164 mg, 30%).
5,9-Anhydro-6-azido-7,8,10-tri-O-benzyl-2,3,4,6-tetradeoxy-
1,2-N,O-isopropylidene-2-(tert-butoxycarbonylamino)-D-
erythro-L-galacto-dec-3-ynitol (22)
Treatment of 20 (100 mg, 0.13 mmol) as described for the prepara-
tion of 8 gave, after column chromatography on silica gel (6:1 cy-
clohexane–EtOAc), first 22 (34 mg, 35%) as a syrup; [ ]D +42.2 (c
= 0.8, CHCl3).
1H NMR (DMSO-d6, 120 °C): = 7.40–7.20 (m, 15 H, 3 C6H5),
4.82 (s, 2 H, PhCH2), 4.74 and 4.60 (2 d, 2 H, J = 11.3 Hz, PhCH2),
4.66 (ddd, 1 H, J1a,2 = 2.3, J1b,2 = 2.5, J2,5 = 1.8 Hz, H-2), 4.55 and
4.49 (2 d, 2 H, J = 12.0 Hz, PhCH2), 4.17 (dd, 1 H, J5,6 = 9.8 Hz, H-
5), 4.09 (dd, 1 H, J1a,1b = 8.8 Hz, H-1a), 3.93 (dd, 1 H, H-1b), 3.68
(dd, 1 H, J6,7 = 9.0 Hz, H-6), 3.66–3.52 (m, 4 H, H-7, H-8, 2 H-10),
3.45 (dd, 1 H, J7,8 = 9.3, J8,9 = 9.0 Hz, H-8), 1.59 and 1.43 (2 s, 6 H,
2 CH3), 1.43 (s, 9 H, t-C4H9).
J6,7 = 9.5 Hz, H-6), 3.72 (dd, 1 H, J9,10a = 6.0, J9,10b = 6.0 Hz, H-9),
3.65 (dd, 1 H, H-7), 3.59 (dd, 1 H, J10a,10b = 10.0 Hz, H-10a), 3.57
(dd, 1 H, H-10b), 1.52 and 1.48 (2 s, 6 H, 2 CH3), 1.43 (s, 9 H, t-
C4H9).
MALDI-TOF MS: m/z = 706.0 (M+ + Na), 722.2 (M+ + K).
MALDI-TOF MS: m/z = 771.2 (M+ + Na), 787.2 (M+ + K).
Anal. Calcd for C39H46N4O7: C, 68.60; H, 6.79; N, 8.21. Found: C,
68.70; H, 6.85; N, 8.29.
Anal. Calcd for C46H53NO8: C, 73.87; H, 7.14; N, 1.87. Found: C,
73.65; H, 7.19; N, 1.68.
Unreacted 20 (29 mg, 29%) was eluted out as the second fraction.
Synthesis 2001, No. 14, 2129–2137 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of -Linked Glycosyl Serine Methylene Isoesters
2135
6,7,8,10-Tetra-O-acetyl-5,9-anhydro-2,3,4-trideoxy-1,2-N,O-
isopropylidene-2-(tert-butoxycarbonylamino)-D-threo-L-galac-
to-decitol (10); Typical Procedure
through Celite and concentrated. A solution of the crude product in
Ac2O (1 mL) was kept at r.t. for 30 min and then concentrated. A
vigorously stirred mixture of the crude acetamido derivative, 20%
Pd(OH)2 on carbon (20 mg), EtOAc (1 mL), and MeOH (1 mL) was
degassed under vacuum and saturated with H2 (by means of a H2-
filled balloon) three times. The suspension was stirred at r.t. for 12
h under a slightly positive pressure of H2 (balloon), then filtered
through a plug of cotton and concentrated. A solution of the crude
product in Ac2O (2 mL) and pyridine (2 mL) was kept at r.t. for 4 h,
and then concentrated. The residue was eluted from a short column
of silica gel (1 10 cm, d h) with 3:1 CH2Cl2–acetone to give 23
(97 mg, 85%) as a syrup; [ ]D –14.6 (c = 0.4, CHCl3).
1H NMR (DMSO-d6, 120 °C): = 6.08 (d, 1 H, J 2,NH = 8.0 Hz, NH),
5.29 (dd, 1 H, J7,8 = 3.0, J8,9 = 0.5 Hz, H-8), 4.98 (d, 1 H, J6,7 = 10.5
Hz, H-7), 4.02 (ddd, 1 H, J5,6 = 9.0 Hz, H-6), 4.02–3.87 (m, 4 H),
3.91 (ddd, 1 H, J9,10a = 4.5, J9,10b = 2.5 Hz, H-9), 3.63–3.60 (m, 1 H,
H-2), 3.42 (ddd, 1 H, J4a,5 = 9.0, J4b,5 = 2.0 Hz, H-5), 2.10–1.82 (4 s,
12 H, 4 CH3CO), 1.65–1.45 (m, 4 H), 1.43 (s, 3 H, CH3), 4.41 (s, 12
H, CH3, t-C4H9).
A vigorously stirred mixture of 8 (100 mg, 0.13 mmol), 20%
Pd(OH)2 on carbon (10 mg), and MeOH (3 mL) was degassed under
vacuum and saturated with H2 (by means of a H2-filled balloon)
three times. The suspension was stirred at r.t. for 12 h under a posi-
tive pressure of H2 (8 bar), then filtered through a plug of cotton and
concentrated. A solution of the crude product in Ac2O (2 mL) and
pyridine (2 mL) was kept at r.t. for 7 h, and then concentrated. The
residue was eluted from a column of silica gel with 2:1 cyclohex-
ane–EtOAc to afford 10 (68 mg, 91%) as a syrup; [ ]D +17.2 (c = 1,
CHCl3).
1H NMR (DMSO-d6, 120 °C): = 5.33 (dd, 1 H, J7,8 = 3.5, J8,9 = 0.5
Hz, H-8), 5.12 (dd, 1 H, J6,7 = 10.0 Hz, H-7), 4.93 (dd, 1 H, J5,6 = 9.0
Hz, H-6), 4.08–3.96 (m, 3 H), 3.92 (dd, 1 H, J1a,2 = 6.0, J1a,1b = 8.5
Hz, H-1a), 3.83–3.82 (m, 1 H, H-2), 3.67 (dd, 1 H, H-1b), 3.55 (ddd,
1 H, J4a,5 = 9.0, J4b,5 = 3.0 Hz, H-5), 2.12–1.95 (4 s, 12 H, 4
CH3CO), 1.70–1.52 (m, 4 H), 1.48 and 1.41 (2 s, 6 H, 2 CH3), 1.40
(s, 9 H, t-C4H9).
MALDI-TOF MS: m/z = 581.9 (M+ + Na), 597.9 (M+ + K).
MALDI-TOF MS: m/z = 583.0 (M+ + Na), 599.0 (M+ + K).
Anal. Calcd for C26H42N2O11: C, 55.90; H, 7.58; N, 5.01. Found:C,
55.95; H, 7.75; N, 5.17.
Anal. Calcd for C26H41NO12: C, 55.80; H, 7.38; N, 2.50. Found: C,
55.71; H, 7.41; N, 2.60.
6-Acetamido-7,8,10-tri-O-acetyl-5,9-anhydro-2,3,4,6-tetra-
deoxy-1,2-N,O-isopropylidene-2-(tert-butoxycarbonylamino)-
D-erythro-L-galacto-decitol (24)
Compound 22 (50 mg, 0.07 mmol) was hydrogenated and acetylat-
ed as described for the preparation of 23. The crude product was
eluted from a short column of silica gel (1 10 cm, d h) with 1:1:1
cyclohexane–EtOAc–CH2Cl2 to afford 24 (34 mg, 87%) as a white
solid; mp 111–113 °C (Et2O); [ ]D –8.3 (c = 0.4, CHCl3).
5,9-Anhydro-6,7,8,10-tetra-O-benzyl-2,3,4-trideoxy-1,2-N,O-
isopropylidene-2-(tert-butoxycarbonylamino)-D-threo-L-galac-
to-decitol (14)
To a warmed (85 °C) and stirred solution of 8 (100 mg, 0.13 mmol)
and freshly recrystallized p-toluenesulfonhydrazide (149 mg, 0.78
mmol) in dimethoxyethane (2 mL) was added 1 M aq NaOAc (0.78
mL) in six portions during 3 h. After an additional 2.5 h at 85 °C,
the mixture was diluted with H2O (1.5 mL) and extracted with
CH2Cl2 (3 15 mL). The organic phase was dried (Na2SO4) and
concentrated. The residue was eluted from a column of silica gel
with cyclohexane–EtOAc (from 5:1 to 4:1) to give 14 (83 mg, 85%)
as a syrup. Compound 8 was identical in all respects to the product
that we prepared by another route.15a
1H NMR (DMSO-d6 D2O, 100 °C): = 5.04 (dd, 1 H, J5,6 = 9.0,
J6,7 = 9.5 Hz, H-6), 4.80 (dd, 1 H, J7,8 = 9.5 Hz, H-7), 4.12 (dd, 1 H,
J9,10a = 5.5, J10a,10b = 12.0 Hz, H-10a), 4.04 (dd, 1 H, J9,10b = 3.0 Hz,
H-10b), 3.89 (dd, 1 H, J1a,2 = 2.5, J1a,1b = 8.8 Hz, H-1a), 3.81–3.78
(m, 1 H, H-2), 3.70 (dd, 1 H, J8,9 = 9.5 Hz, H-8), 3.68 (ddd, 1 H, H-
9), 3.63 (dd, 1 H, J1b,2 = 1.8 Hz, H-1b), 3.44 (ddd, 1 H, J4a,5 = 9.0,
J
4b,5 = 3.0 Hz, H-5), 2.01–1.79 (4 s, 12 H, 4 CH3CO), 1.80–1.60 (m,
6,7,8,10-Tetra-O-acetyl-5,9-anhydro-2,3,4-trideoxy-1,2-N,O-
isopropylidene-2-(tert-butoxycarbonylamino)-D-erythro-L-
galacto-decitol (11)
4 H), 1.49 and 1.42 (2 s, 6 H, 2 CH3), 1.44 (s, 9 H, t-C4H9).
MALDI-TOF MS: m/z = 581.6 (M+ + Na), 597.8 (M+ + K).
Compound 9 (285 mg, 0.38 mmol) was hydrogenated and acetylat-
ed as described for the preparation of 10. The crude product was
eluted from a column of silica gel with 5:2 cyclohexane–EtOAc to
give 11 (192 mg, 90%) as a syrup; [ ]D +8.3 (c = 1.5, CHCl3).
1H NMR (DMSO-d6, 120 °C): = 5.18 (dd, 1 H, J6,7 = 9.5, J7,8 = 9.5
Hz, H-7), 4.88 (dd, 1 H, J8.9 = 10.0 Hz, H-8), 4.72 (dd, 1 H, J5,6 = 9.5
Hz, H-6), 4.14–4.06 (m, 2 H, 2 H-10), 3.91 (dd, 1 H, J1a,1b = 8.5,
Anal. Calcd for C26H42N2O11: C, 55.90; H, 7.58; N, 5.01. Found: C,
55.75; H, 7.65; N, 5.12.
6,7,8,10-Tetra-O-acetyl-5,9-anhydro-2,3,4-trideoxy-2-(tert-
butoxycarbonylamino)-D-threo-L-galacto-deconic Acid (12);
Typical Procedure
To a cooled (0 °C), stirred solution of 10 (150 mg, 0.27 mmol) in
acetone (4 mL) was added freshly prepared Jones’ reagent (1 M,
0.81 mL, 0.81 mmol). The mixture was allowed to warm to r.t. in 30
min, stirred at r.t. for an additional 3 h, and then diluted with pro-
pan-2-ol (0.35 mL). To the orange suspension was added dropwise
propan-2-ol until a green color was observed, then the reaction mix-
ture was diluted with CH2Cl2 (60 mL) and washed with brine
(3 20 mL). The organic phase was dried (Na2SO4) and concentrat-
ed to afford 12 (129 mg, 90%) as a syrup 90% pure by 1H NMR
analysis.
J1a,2 = 3.0 Hz, H-1a), 3.86–3.30 (m, 2 H, H-2, H-9), 3.66 (dd, 1 H,
J1b,2 = 2.0 Hz, H-1b), 3.59 (ddd, 1 H, J4a,5 = 9.2, J4b,5 = 2.8 Hz, H-5),
2.00 and 1.94 (4 s, 12 H, 4 CH3CO), 1.65–1.49 (m, 4 H), 1.47 and
1.43 (2 s, 6 H, 2 CH3),1.41 (s, 9 H, t-C4H9).
MALDI-TOF MS: m/z = 582.7 (M+ + Na), 599.1 (M+ + K).
Anal. Calcd for C26H41NO12: C, 55.80; H, 7.38; N, 2.50.Found: C,
55.91; H, 7.26; N, 2.61.
6-Acetamido-7,8,10-tri-O-acetyl-5,9-anhydro-2,3,4,6-tetra-
deoxy-1,2-N,O-isopropylidene-2-(tert-butoxycarbonylamino)-
D-threo-L-galacto-decitol (23); Typical Procedure
A vigorously stirred mixture of 21 (140 mg, 0.21 mmol), 20%
Pd(OH)2 on carbon (20 mg), EtOAc (1 mL), and MeOH (1 mL) was
degassed under vacuum and saturated with H2 (by means of a H2-
filled balloon) three times. The suspension was stirred at r.t. for 2 h
under a slightly positive pressure of H2 (balloon), then filtered
1H NMR: = 5.44 (dd, 1 H, J7,8 = 3.0, J8,9 = 0.5 Hz, H-8), 5.21–5.15
(m, 1 H, NH), 5.11 (dd, 1 H, J5,6 = 9.3, J6,7 = 10.0 Hz, H-6), 5.03
(dd, 1 H, H-7), 4.29–4.27 (m, 1 H, H-2), 4.12 (dd, 1 H, J9,10a = 6.0,
J10a,10b = 11.0 Hz, H-10a), 4.10 (dd, 1 H, J9,10b = 6.0 Hz, H-10b),
3.89 (ddd, 1 H, H-9), 3.49 (ddd, 1 H, J4a,5 = 9.3, J4b,5 = 3.0 Hz, H-5),
2.18–2.00 (m, 4 H), 1.48 (s, 9 H, t-C4H9).
Synthesis 2001, No. 14, 2129–2137 ISSN 0039-7881 © Thieme Stuttgart · New York

2136
A. Dondoni et al.
PAPER
6,7,8,10-Tetra-O-acetyl-5,9-anhydro-2,3,4-trideoxy-2-(tert-
butoxycarbonylamino)-D-erythro-L-galacto-deconic Acid (13)
Oxidation of 11 (147 mg, 0.26 mmol) as described for the prepara-
tion of 12 gave 13 (120 mg, 90%) as a syrup 95% pure by H
NMR analysis.
1H NMR: = 5.19 (dd, 1 H, J6.7 = 9.5, J7,8 = 9.5 Hz, H-7), 5.02 (dd,
1 H, J8,9 = 10.0 Hz, H-8), 4.84 (dd, 1 H, J5,6 = 9.0 Hz, H-6), 4.23–
4.00 (m, 4 H), 3.64–3.52 (m, 2 H), 2.10–2.00 (4 s, 12 H, 4 CH3CO),
1.43 (s, 9 H, t-C4H9).
H, 4 CH3CO), 2.01–1.44 (m, 4 H, 2 H-3, 2 H-4), 1.46 (s, 9 H, t-
C4H9).
MALDI-TOF MS: m/z = 570.9 (M+ + Na), 586.7 (M+ + K).
1
Anal. Calcd for C24H37NO13: C, 52.65; H, 6.81; N, 2.56. Found:C,
52.80; H, 6.79; N, 2.54.
Methyl 6-Acetamido-7,8,10-tri-O-acetyl-5,9-anhydro-2,3,4,6-
tetradeoxy-2-(tert-butoxycarbonylamino)-D-threo-L-galacto-
deconate (25 Me Ester)
Treatment of a solution of crude acid 25 in 1:1 Et2O–MeOH with
ethereal diazomethane at 0 °C for 5 min gave, after chromatography
on a short column of silica gel (1 10 cm, d h; 2:1 CH2Cl2–ace-
tone), the methyl ester of 25 as a syrup; [ ]D –7.5 (c = 0.5, CHCl3).
6-Acetamido-7,8,10-tri-O-acetyl-5,9-anhydro-2,3,4,6-tetra-de-
oxy-2-(tert-butoxycarbonylamino)-D-threo-L-galacto-deconic
Acid (25)
Oxidation of 23 (97 mg, 0.17 mmol) as described for the preparation
1H NMR: = 5.70 (d, 1 H, J = 8.5 Hz, NH), 5.37 (dd, 1 H, J7,8 = 3.5,
1
of 12 gave 25 (68 mg, 75%) as an white foam 90% pure by H
J8,9 = 0.5 Hz, H-8), 4.97 (dd, 1 H, J6,7 = 10.5 Hz, H-7), 4.68 (ddd, 1
NMR analysis.
H, J5,6 = 9.0 Hz, H-6),4.12 (dd, 1 H, J9,10a = 6.5, J10a,10b = 11.0 Hz,
H-10a), 4.10 (dd, 1 H, J9,10b = 9.0 Hz, H-10b), 4.05–4.03 (m, 1 H,
H-2), 3.84 (ddd, 1 H, H-9), 3.77 (s, 3 H, OCH3), 3.40 (ddd, 1 H,
1H NMR: (selected data): = 5.61–5.56 (m, 1 H, NH), 5.20–4.96
(m, 3 H), 4.32–3.88 (m, 2 H), 3.75–3.22 (m, 2 H), 3.10–3.07 (m, 1
H), 2.14–1.96 (4 s, 12 H, 4 CH3CO), 1.65–1.47 (m, 4 H), 1.32 (s, 9
H, t-C4H9).
J4a,5 = 9.2, J4b,5 = 0.5 Hz, H-5), 2.14–2.00 (4 s,12 H, 4 CH3CO),
1.75–1.56 (m, 4 H), 1.43 (s, 9 H, t-C4H9).
MALDI-TOF MS: m/z = 569.5 (M+ + Na), 585.7 (M+ + K).
6-Acetamido-7,8,10-tri-O-acetyl-5,9-anhydro-2,3,4,6-tetra-
deoxy-2-(tert-butoxycarbonylamino)-D-erythro-L-galacto-
deconic Acid (26)
Anal. Calcd for C24H38N2O12: C, 52.74; H, 7.01; N, 5.13. Found: C,
52.81; H, 7.09; N, 5.00.
Oxidation of 24 (80 mg, 0.14 mmol) as described for the preparation
1
of 12 gave 26 (53 mg, 71%) as a syrup 90% pure by H NMR
Methyl 6-Acetamido-7,8,10-tri-O-acetyl-5,9-anhydro-2,3,4,6-
tetradeoxy-2-(tert-butoxycarbonylamino)-D-erythro-L-galacto-
deconate (26 Me Ester)
Treatment of a solution of crude acid 26 in 1:1 Et2O–MeOH with
ethereal diazomethane at 0 °C for 5 min gave, after column chroma-
tography on silica gel (2:1 toluene–acetone), the methyl ester of 26
as a syrup; [ ]D –25.5 (c = 0.9, CHCl3); [ ]D –26.2 (c = 0.8, CH2Cl2)
{Lit.18 [ ]D –27 (c = 1.0, CH2Cl2)}.
analysis.
1H NMR: (selected data) = 5.61–5.56 (m, 1 H, NH), 5.10–4.96 (m,
2 H), 4.23–3.98 (m, 3 H), 3.79–3.32 (m, 2 H, 2 H-10), 3.14–3.11 (m,
1 H, H-5), 2.14–1.96 (4 s,12 H, 4 CH3CO), 1.65–1.47 (m, 4 H), 1.32
(s, 9 H, t-C4H9).
Methyl 6,7,8,10-Tetra-O-acetyl-5,9-anhydro-2,3,4-trideoxy-2-
(tert-butoxycarbonylamino)-D-threo-L-galacto-deconate (12 Me
Ester)
The 1H NMR spectrum of the metyl ester of 26 was identical to that
reported in Ref.18
Treatment of a solution of crude acid 12 in1:1 Et2O–MeOH with
ethereal diazomethane at 0 °C for 5 min gave, after column chroma-
tography on silica gel with 1:1 cyclohexane–EtOAc, the methyl es-
ter of 12 as a syrup; [ ]D +4.6 (c = 0.9, CHCl3).
6,7,8,10-Tetra-O-acetyl-5,9-anhydro-2,3,4-trideoxy-2-(9-
fluorenylmethoxycarbonylamino)-D-threo-L-galacto-decitol
(27)
1H NMR: = 5.43 (dd, 1 H, J7,8 = 3.5, J8,9 = 1.0 Hz, H-8), 5.09 (dd,
1 H, J5,6 = 9.5, J6,7 = 10.0 Hz, H-6), 5.02 (dd, 1 H, H-7), 4.33–4.24
(m, 1 H, H-2), 4.13 (dd, 1 H, J9,10a = 6.7, J10a,10b = 11.0 Hz, H-10a),
4.07 (dd, 1 H, J9,10b = 6.5 Hz, H-10b), 3.87 (ddd, 1 H, H-9), 3.76 (s,
3 H, OCH3), 3.46 (ddd, 1 H, J4a,5 = 9.0, J4b,5 = 2.5 Hz, H-5), 2.19–
2.00 (3 s, 12 H, 4 CH3CO), 1.90–1.75 (m, 2 H), 1.69–1.55 (m, 2 H),
1.43 (s, 9 H, t-C4H9).
To a cooled (0 °C), stirred solution of 10 (170 mg, 0.31 mmol) in
CH2Cl2 (4 mL) was added dropwise trifluoroacetic acid (1.0 mL).
The mixture was stirred at 0 °C for 30 min, and then allowed to
warm up to r.t. After an additional 30 min at r.t., the solution was
coevaporated with toluene (3 20 mL). To a solution of the residue
in H2O (2 mL) and MeCN (2 mL) was added at r.t. a solution of N-
(9-fluorenylmethoxycarbonyloxy)succinimide (125 mg, 0.37
mmol) in MeCN (1 mL) and then freshly distilled Et3N (128 L,
0.93 mmol) in order to maintain the pH of the reaction mixture at
ca. 9. After 45 min the TLC analysis (2:1 EtOAc–cyclohexane) in-
dicated the disappearance of the starting material. 0.1 M HCl was
added until pH = 2. The mixture was diluted with CH2Cl2 (20 mL)
and the phases were separated. The aqueous layer was extracted
with CH2Cl2 (2 10 mL), the combined organic layers were dried
(Na2SO4), filtered, and concentrated. The residue was eluted from a
column of silica gel with EtOAc–cyclohexane (from 1:1 to 2:1) to
afford 27 (159 mg, 80%) as a white solid; mp 82–85 °C (EtOAc–
cyclohexane); [ ]D –5.6 (c = 0.9, CHCl3).
MALDI-TOF MS: m/z = 570.6 (M+ + Na), 586.8 (M+ + K).
Anal. Calcd for C24H37NO13: C, 52.65; H, 6.81; N, 2.56. Found: C,
52.56; H, 6.90; N, 2.60.
Methyl 6,7,8,10-Tetra-O-acetyl-5,9-anhydro-2,3,4-trideoxy-2-
(tert-butoxycarbonylamino)-D-erythro-L-galacto-deconate (13
Me Ester)
Treatment of a solution of crude acid 13 in1:1 Et2O–MeOH with
ethereal diazomethane at 0 °C for 5 min gave, after column chroma-
tography on silica gel (2:1 EtOAc–cyclohexane), the methyl ester of
13 as a white solid; mp 109–111 °C (cyclohexane–EtOAc); [ ]D –
4.0 (c = 1, CHCl3).
1H NMR: = 7.82–7.78, 7.66–7.61, and 7.48–7.33 (3 m, 8 Harom),
5.42 (dd, 1 H, J7,8 = 3.0, J8,9 = 1.0 Hz, H-8), 5.11 (dd, 1 H, J5,6 = 9.0,
1H NMR: = 5.19 (dd, 1 H, J6,7 = 9.4, J7,8 = 9.3 Hz, H-7), 5.06 (d,
1 H, J2,NH = 8.0 Hz, NH), 5.05 (dd, 1 H, J8,9 = 10.0 Hz, H-8), 4.89
(dd, 1 H, J5,6 = 9.9 Hz, H-6), 4.33–4.25 (m, 1 H, H-2), 4.24 (dd, 1
H, J9,10a = 5.1, J10a,10b = 12.3 Hz, H-10a), 4.11 (dd, 1 H, J9,10b = 2.2
Hz, H-10b), 3.76 (s, 3 H, OCH3), 3.65 (ddd, 1 H, H-9), 3.48 (ddd, 1
H, J4a,5 = 2.6, J4b,5 = 8.0 Hz, H-5), 2.11, 2.06, 2.04 and 2.02 (4 s, 12
J6,7 = 10.0 Hz, H-6), 5.05 (br s, 1 H, NH), 5.02 (dd, 1 H, H-7), 4.54
(dd, 1 H, J = 6.5, 10.5 Hz, CH2-Fmoc), 4.44 (dd, 1 H, J = 6.3, 10.5
Hz, CH2-Fmoc), 4.24 (dd, 1 H, J = 6.3, 6.5 Hz, CH-Fmoc), 4.22–
4.19 (m, 1 H, H-2), 4.13 (dd, 1 H, J10a,10b = 11.0, J9,10a = 7.0 Hz, H-
10a), 4.04 (dd, 1 H, J9,10b = 6.0 Hz, H-10b), 3.77 (ddd, 1 H, H-9),
3.70–3.59 (m, 4 H), 3.43 (ddd, 1 H, J4a,5 = 8.2, J4b,5 = 3.3 Hz, H-5),
2.13, 2.03 and 2.00 (3 s, 12 H, 4 CH3CO), 1.72–1.60 (m, 4 H).
Synthesis 2001, No. 14, 2129–2137 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of -Linked Glycosyl Serine Methylene Isoesters
2137
Anal. Calcd for C33H39NO12: C, 61.77; H, 6.13; N, 2.18. Found: C,
61.99; H, 6.00; N, 2.40.
(4) (a) Sjölin, P.; George, S. K.; Bergquist, K.-E.; Roy, S.;
Svensson, A.; Kihlberg, J. J. Chem. Soc., Perkin Trans. 1
1999, 1731. (b) Sjölin, P.; Kihlberg, J. J. Org. Chem. 2001,
66, 2957. (c) Tamura, J.; Nishihara, J. J. Org. Chem. 2001,
66, 3074.
6,7,8,10-Tetra-O-acetyl-5,9-anhydro-2,3,4-trideoxy-2-(9-
fluorenylmethoxycarbonylamino)-D-threo-L-galacto-deconic
Acid (28)
Treatment of 27 (98 mg, 0.15 mmol) as described for the prepara-
tion of 12 gave 28 (95 mg, 95%) as a syrup 95% pure by 1H NMR
analysis.
1H NMR: = 7.83–7.76, 7.67–7.57, and 7.49–7.31 (3 m, 8 Harom),
5.49 (d, 1 H, JNH,2 = 7.8 Hz, NH), 5.43 (dd, 1 H, J7,8 = 3.0, J8,9 = 1.0
Hz, H-8), 5.11 (dd, 1 H, J5,6 = 9.0, J6,7 = 10.0 Hz, H-6), 5.03 (dd, 1
H, H-7), 4.52 (dd, 1 H, J = 7.0,10.5 Hz, CH2-Fmoc), 4.44–4.34 (m,
2 H, CH2-Fmoc, H-2), 4.25 (dd, 1 H, J = 6.5, 7.0 Hz, CH-Fmoc),
4.13 (dd, 1 H, J9,10a = 7.0, J10a,10b = 11.5 Hz, H-10a), 4.05 (dd, 1 H,
(5) For recent methods not reviewed in Ref.1 see: Nishikawa,
T.; Ishikawa, M.; Wada, K.; Isobe, M. Synlett 2001, 945.
(6) For addition of iodo-zinc reagent bearing an oxazolidinone
ring to a glycal, see: Dorgan, B. J.; Jackson, R. F. W. Synlett
1996, 859.
(7) For coupling of oxazolidinone ethanal with glycosyl
samarium derivatives, see: Urban, D.; Skrydstrup, T.; Beau,
J.-M. Chem.Commun. 1998, 955.
(8) For coupling of oxazolidine silyl enol ether with
glycosyltrichloroacetimidate, see: Dondoni, A.; Marra, A.;
Massi, A. J. Org. Chem. 1999, 64, 933.
(9) For a detailed experimental procedure and physical and
spectroscopic data of some sugar lactones, see: Dondoni, A.;
Scherrmann, M.-C. J. Org. Chem. 1994, 59, 6404.
(10) Serrat, X.; Cabarrocas, G.; Rafel, S.; Ventura, M.; Linden,
A.; Villalgordo, J. M. Tetrahedron: Asymmetry 1999, 10,
3417.
J9,10b = 6.0 Hz, H-10b), 3.81 (ddd, 1 H, H-9), 3.48–3.43 (m, 1 H, H-
5), 2.17, 2.05, 2.03 and 2.01 (4 s, 12 H, 4 CH3CO),1.80–1.54 (m, 4
H).
Methyl 6,7,8,10-Tetra-O-acetyl-5,9-anhydro-2,3,4-trideoxy-2-
(9-fluorenylmethoxycarbonylamino)-D-threo-L-galacto-deco-
nate (28 Me Ester)
(11) (a) For the synthesis of this aldehyde from serine via a
reduction-oxidation procedure avoiding substantial
racemization, see: Dondoni, A.; Perrone, D. Synthesis 1997,
527. (b) Dondoni, A.; Perrone, D. Org. Synth. 1999, 77, 64.
(12) Evidently the alkyne 1 {[ ]D +90 (c = 0.7, CHCl3)} is the
enantiomer of the product described in Ref.10 which in fact
was prepared starting from L-serine. Therefore the optical
rotation value quoted in Ref.10 {([ ]D +88 (c = 1.05, CHCl3)}
should be changed into a negative value in agreement with
earlier data from the literature quoted in the same
publication.
Treatment of a solution of crude acid 28 in 1:1 Et2O–MeOH with
ethereal diazomethane at 0 °C for 5 min gave, after column chroma-
tography on silica gel (2:1 EtOAc–cyclohexane), the methyl ester
28 as a syrup; [ ]D +1.5 (c = 1.2, CHCl3).
1H NMR: = 7.83–7.75, 7.70–7.57, and 7.47–7.31 (3 m, 8 Harom),
5.43 (dd, 1 H, J7,8 = 3.0, J8,9 = 1.0 Hz, H-8), 5.38 (d, 1 H, JNH,2 = 7.5
Hz, NH), 5.11 (dd, 1 H, J5,6 = 9.5, J6,7 = 10.0 Hz, H-6), 5.03 (dd, 1
H, H-7), 4.49 (dd, 1 H, J = 6.5, 10.5 Hz, CH2Fmoc), 4.39 (dd, 1 H,
J = 7.0, 10.5 Hz, CH2-Fmoc), 4.38–4.32 (m, 1 H, H-2), 4.25 (dd, 1
H, J = 6.5, 7.0 Hz, CH-Fmoc), 4.14 (dd, 1 H, J9,10a = 7.0,
J10a,10b = 11.0 Hz, H-10a), 4.06 (dd, 1 H, J9,10b = 5.5 Hz, H-10b),
3.82 (ddd, 1 H, H-9), 3.79 (s, 3 H, OCH3), 3.46 (ddd, 1 H, J4a,5 = 9.0,
(13) (a) C-Glycoside Synthesis; Postema, M. H. D., Ed.; CRC
Press: Boca Raton, 1995, 57–60. (b) Lowary, T.; Meldal,
M.; Helmboldt, A.; Vasella, A.; Bock, K. J. Org. Chem.
1998, 63, 9657.
J4b,5 = 3.0 Hz, H-5), 2.18, 2.06, 2.04 and 2.00 (4 s, 12 H, 4 CH3CO),
1.95–1.52 (m, 4 H).
(14) Dondoni, A.; Marra, A.; Pasti, C. Tetrahedron: Asymmetry
2000, 11, 305.
Anal. Calcd for C34H39NO13: C, 60.98; H, 5.87; N, 2.09. Found: C,
60.60; H, 6.00; N, 2.13.
(15) The anomerization free one-step transformation of the
oxazolidine ring into the glycinyl group was demonstrated in
several instances in earlier work from our laboratory. See:
(a) Dondoni, A.; Marra, A.; Massi, A. Tetrahedron 1998, 54,
2827. (b) Dondoni, A.; Marra, A.; Massi, A. Chem.
Commun. 1998, 1741. (c) Dondoni, A.; Mariotti, G.; Marra,
A. Tetrahedron Lett. 2000, 41, 3483. (d) Dondoni, A.;
Giovannini, P. P.; Marra, A. J. Chem. Soc., Perkin Trans. 1,
2001, in press.
Acknowledgement
We thank Mr. P. Formaglio (University of Ferrara, Italy) for NMR
measurements. This research was financially supported by
MURST, COFIN-2000 (Italy). We are grateful to Ajinomoto Co.,
Inc. (Tokyo, Japan) for an unrestricted grant.
(16) Marcaurelle, L. A.; Bertozzi, C. R. J. Am. Chem. Soc. 2001,
123, 1587; and references cited therein.
References
(17) (a) Jensen, K. J.; Hansen, P. R.; Venugopal, D.; Barany, G.
J. Am. Chem. Soc. 1996, 118, 3148. (b) Mitchell, S. A.;
Pratt, M. R.; Hruby, V. J.; Polt, R. J. Org. Chem. 2001, 66,
2327; and references therein.
(18) Fuchss, T.; Schmidt, R. R. Synthesis 1998, 753.
(19) Armarego, W. L. F.; Perrin, D. D. Purification of Laboratory
Chemicals; Butterworth–Heinemann: Oxford, 1996, 4th ed.
(20) Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43,
2923.
(1) Dondoni, A.; Marra, A. Chem. Rev. 2000, 100, 4395.
(2) (a) Varki, A. Glycobiology 1993, 3, 97. (b) Dwek, R. A.
Chem. Rev. 1996, 96, 683. (c) Imperiali, B. Acc. Chem. Res.
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Cold Spring Harbor Laboratory Press: New York, 1999.
(3) (a) Jansson, A. M.; Meldal, M.; Bock, K. J. Chem. Soc.,
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Synthesis 2001, No. 14, 2129–2137 ISSN 0039-7881 © Thieme Stuttgart · New York