Synthesis of amino-substituted hexo- and heptopyranoses from D-galactose

Article abstract of DOI:10.1016/S0008-6215(03)00382-3

After condensation of D-galactose with two equivalents of acetone, the last free hydroxy group was transformed into an acylated amino group by Swern oxidation, oxime formation, LiAlH₄ reduction and acylation. The intermediate aldehyde was homol

Full text of DOI:10.1016/S0008-6215(03)00382-3

Carbohydrate Research 338 (2003) 2375ꢀ2385
/
www.elsevier.com/locate/carres
Synthesis of amino-substituted hexo- and heptopyranoses from
D-galactose
Benedikt Streicher, Bernhard Wunsch*
¨
Institut fur Pharmazeutische und Medizinische Chemie der Westfalischen Wilhelms-Universitat Munster, Hittorfstraße 58-62, D-48149 Munster,
¨ ¨ ¨ ¨ ¨
Germany
Received 18 June 2003; accepted 23 July 2003
Abstract
After condensation of
D-galactose with two equivalents of acetone, the last free hydroxy group was transformed into an acylated
amino group by Swern oxidation, oxime formation, LiAlH4 reduction and acylation. The intermediate aldehyde was homologated
with the Wittig reagent, (methoxymethyl)triphenylphosphonium chloride, to afford, after careful hydrolysis, a homologous
heptodialdo-1,5-pyranose. Condensation of the aldehyde with hydroxylamine and subsequent LiAlH4 reduction provided a bis-
O,O-isopropylidene-protected 7-amino-6,7-dideoxygalactoheptopyranose, which was acylated with various carboxylic acid
derivatives. The isopropylidene protective groups were cleaved by careful hydrolysis or alcoholysis to yield 6-acylamino-6-deoxy-
galactopyranoses and 7-acylamino-6,7-dideoxy-galactohepto-pyranoses.
# 2003 Elsevier Ltd. All rights reserved.
Keywords: 6-Aminogalactopyranoses; 7-Aminoglactoheptopyranoses; Galactose; Homologation
1. Introduction
within the central nervous system, in particular for the
class of opioid receptors.10 (Fig. 1)
This communication deals with the synthesis of novel
Monosaccharides with amino substituents in different
ring positions are of interest as substructures of amino-
glycoside antibiotics, e.g., kanamycin, gentamicin, or
neomycin.1 Moreover, pyranoses 1 with aminoalkyl
substituents in position 5 will be used as starting
compounds for the synthesis of selectively substituted
tetrahydropyran derivatives 2 and bicyclic ring systems
3.2ꢀ4 In the literature only a few examples for 7-amino-
6-amino-6-deoxyhexopyranoses (1a) (nꢁ
no-6,7-dideoxyheptopyranoses (1b) (nꢁ2), which are
derived from the monosaccharide, -galactose (4).
/1) and 7-ami-
/
D
7-deoxyheptopyranoses 1b and 2b (nꢁ
The bicyclo[3.3.1]nonane derivative 3b (nꢁ
/
2) are given.5ꢀ7
2) reveals
/
structural similarity to the morphan ring system, which
itself represents a substructure of the opioid analgesic
morphine.8 Following the strategy of modifying mono-
saccharides allows the stereoselective introduction of
various substituents in different ring positions with
defined stereochemistry in 2 and 3.9,10 The products 2
and 3 should be developed as novel ligands for receptors
* Corresponding author. Tel.: ꢂ
251-8332144.
E-mail address: wuensch@uni-muenster.de (B. Wunsch).
/
49-251-8333311; fax: ꢂ
/
49-
Fig. 1. Conversion of 6- or 7-amino-6- or 7-deoxy-D-galacto-
hexo- and heptopyranoses to selectively substituted tetrahy-
dropyrans.
¨
0008-6215/03/$ - see front matter # 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0008-6215(03)00382-3

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/
2385
¨
reaction of 10aꢀ/c with NaCN failed to give the nitrile
11. Several modifications were investigated including
variation of the CNꢃ source (LiCN, NaCN, KCN,
TMS-CN, KCN and 18-crown-6), the CNꢃ-amount (1
to 30 equivalents), the solvent (e.g., acetone, acetonitrile,
DMF, Me2SO, triethyleneglycol) and the reaction
temperature (up to 200 8C). Finally, the isolation of a
small amount of the nitrile 11 (4.2% yield) succeeded
after heating the methanesulfonate 10c with LiCN in
DMF for 17 h. Obviously the nucleophilic substitution
at the methylene group of 10aꢀc is impeded by
/
branching in the b-position. (Scheme 2)
The next homologation was performed by
a
Wittig reaction. The aldehyde 6 was condensed with
(methoxymethyl)triphenylphosphonium chloride
(Ph3PCH2OCH3Cl)16,17 and potassium tert-butoxide
(KOtBu) to afford the diastereomeric enolethers (Z)-
12 and (E)-1216 in the ratio 63:37. The aldehyde 13 was
obtained in 90% yield after careful hydrolysis of the
diastereomeric enolethers 12 with HCl in acetone. In
contrast to literature reports,16,17 addition of toxic
Hg(OAc)2 was not necessary. However, the formation
of small amounts of the hemiacetals 18a,b could not be
completely suppressed even under very mild hydrolysis
conditions (Scheme 3) (compare Scheme 4).
NaBH4 reduction of the aldehyde 13 provided the bis-
O-isopropylidene protected galactoheptopyranose deri-
vative 14. Condensation of 13 with hydroxylamine
yielded the oxime 15, which was reduced with LiAlH4
to furnish the primary amine 16. Acylation of the
primary amine with different acyl chlorides afforded
Scheme 1. Reagents and reaction conditions: (a) lit.11; (b)
Me2SO, (COCl)2, Et3N, CH2Cl2, ꢃ70 8C, 67%; (c) H2NOH×
HCl, NaOAc, CH3OH, rt, 76%; (d) LiAlH4, Et2O, rt, 69%; (e)
RCOCl, Et3N, CH2Cl2, rt, 9a: 76%; 9b: 85%; 9c: 69%; (f) H2,
Raney Ni, Ac2O, NaOAc, 70 bar, 80 8C, 9d: 64%.
/
/
2. Results and discussion
the amides 17aꢀ
/
c in 72ꢀ79% yield.
/
According to a literature report11
D-galactopyranose (4)
During hydrolysis of the diastereomeric enolethers 12,
formation of side products, which resulted from addi-
tional hydrolysis of the adjacent acetonide protective
group, could not be completely avoided. In order to
elucidate the structure of these side products, hydrolysis
was performed under severe hydrolysis conditions: 2 N
H2SO4 in acetone for 75 min at reflux temperature.
Since complete purification of the hydrolysis products
18a,b failed, and the product contained two isomers
has been transformed with acetone, CuSO4 and a
catalytic amount of H2SO4 into the bisacetonide 5.
Swern oxidation of the bisacetonide 5 provided the
aldehyde 6,12 which reacted with hydroxylamine to give
the oxime 7.13 The 6-amino-6-deoxygalactopyranose
derivative 8 was obtained by LiAlH4 reduction of the
oxime 7. Subsequent acylation of the primary amine 8
with various carboxylic acid chlorides gave the amides
1
according to the H NMR spectrum, the crude product
9aꢀc in good yield. Alternatively the oxime 7 was
/
reduced with H2 (70 bar) and Raney nickel in the
solvent, acetic anhydride, leading directly to the acet-
amide 9d in 64% yield (Scheme 1).
The initial plan for the synthesis of 7-amino-6,7-
dideoxy-heptopyranoses scheduled homologation of a
hexopyranose derivative by introduction of a cyano
group. For this purpose the free hydroxy group of 5 was
activated for nucleophilic substitution. The bromide 10a
was prepared by an Appel reaction14 of the alcohol 5
with triphenylphosphane and tetrabromomethane. The
sulfonates 10b13,15 and 10c were available by reaction of
the alcohol 5 with p-toluenesulfonyl chloride and
methanesulfonyl chloride, respectively. However, the
Scheme 2. Reagents and reaction conditions: (a) CBr4, PPh3,
CH2Cl2, ꢃ
/
60 8C, 11%; (b) p-TsCl, pyridine, rt, 94%; (c) MsCl,
pyridine, rt, 81%; (d) 10c, LiCN, DMF, 110 8C, 4.2%.

B. Streicher, B. Wunsch / Carbohydrate Research 338 (2003) 2375ꢀ
/
2385
2377
¨
Scheme 3. Reagents and reaction conditions: (a) CH3OCH2PPh3Cl, KOtBu, THF, ꢃ
78 8C, 63%; (b) Me2CO, 2 N HCl, rt, 95%; (c)
/
NaBH4, EtOH, rt, 63%; (d) H2NOH×
/HCl, NaOAc, CH3OH, rt, 63%; (e) LiAlH4, Et2O, rt, 46%; (f) RCOCl, Et3N, CH2Cl2, rt, 17a:
72%; 17b: 79%; 17c: 78%.
of 19a and 19b differ significantly in the signal structure
of the other 6-H revealing no coupling with 7-H: in the
spectrum of 19a, a large coupling constant between 6-H
and 5-H (J5,6 8.1 Hz) is observed, whereas no coupling
(J5,6 0 Hz) of these protons is seen for the diastereomer
19b. These spectroscopic data are in accordance with the
(7R)- and (7S)-configuration for 19a and 19b, respec-
tively.
Hydrolysis of the 6-benzoylamino-6-deoxy-hexopy-
ranose (9a) furnished a 1:1 mixture of the anomeric
hemiacetals 20a and 21a in 79.3% yield. Cleavage of the
O-isopropylidene protective groups of 9a in ethanol in
the presence of a strong acidic ion-exchange resin led to
the ethyl glycosides 20c, 21c and 22c. Whereas the a-
anomer of the ethyl pyranoside 20c could be isolated in
23.6%, yield the b-anomer 21c and the ring-contracted
diastereomeric furanoside 22c could not be separated.
Flash chromatography yielded a mixture of 21c and 22c
(37.6%), which contained predominantly the furanosides
Scheme 4. Reagents and reaction conditions: (a) Me2CO, 2 N
H2SO4, 56 8C; (b) C6H5COCl, Et3N, DMAP, CH2Cl2, rt, 19a:
24%; 19b: 47%.
22c (21c:22cꢁ18:82). (Scheme 5)
/
Similar observations were made during alcoholysis of
the corresponding 7-benzoylamino-6,7-dideoxyhepto-
pyranose (17a). Heating of 17a with methanol and an
acidic ion-exchange resin provided the methyl acetals
23b, 24b and 25b. Flash chromatography yielded the a-
anomeric methyl heptopyranoside 23b (19.8%) and a
small amount of the corresponding b-anomer 24b
(4.9%). However, an anomeric mixture of the methyl
was acylated with an excess of benzoyl chloride.
Separation of the resulting isomeric dibenzoates 19a
and 19b was accomplished by flash chromatography to
obtain 19a and 19b in 24 and 47% yield, respectively.
According to the 1H NMR spectra, a new five-
membered acetalic moiety has been formed. We presume
that the configuration of the new stereogenic center in
position 7 of 19a and 19b is R and S, respectively. The
1H NMR spectra of both diastereomers display similar
doublets for the protons in position 7 (19a: d, J6,7
4.4.Hz; 19b: d, J6,7 5.9 Hz), indicating coupling of 7-H
with only one proton in position 6. However, the spectra
heptofuranoside 25b (a-25b:b-25bꢀ/65:35) was isolated
as main product (67.7%). The corresponding ethyl
glycosides were prepared in an analogous manner by
heating of 17a with ethanol and an acidic ion-exchange
resin. Whereas the a-anomer 23c was isolated in 25.5%
yield, the b-anomer 24c could not be separated from the

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B. Streicher, B. Wunsch / Carbohydrate Research 338 (2003) 2375ꢀ2385
/
¨
Scheme 5. Reagents and reaction conditions: (a) strong acidic ion-exchange resin, H2O, 100 8C, 79%; (b) strong acidic ion-exchange
resin, EtOH, 78 8C, 20c: 24%; 21c, 22c: 38%; (c) strong acidic ion-exchange resin, CH3OH, 65 8C, 23b: 20%; 24b: 4.9%; 25b: 68%; (d)
strong acidic ion-exchange resin, EtOH, 78 8C, 23c: 26%; 24c, 25c: 74%.
ethyl heptofuranoside 25c. Thus, a mixture of 24c and
25c (24c:25cꢁ10:90) was obtained in 73.6% yield.
In summary, the synthesis of various 6-amino sub-
stituted hexopyranoses 8, 9aꢀd and 7-amino-substituted
heptopyranoses 16, 17aꢀc starting from a- -galactose is
presented. Preliminary investigations demonstrate, that
removal of the O,O-isopropylidene protective groups
succeeds with water, methanol and ethanol to afford the
using a 1.0-dm tube; concentration c (g/100 mL);
temperature 20 8C. Elemental analyses (CHN) were
/
determined on a Rapid (Heraeus) and on a Perkinꢀ
Elmer Elemental Analyzer, model 240. Mass spectra
were measured on a HewlettꢀPackard 5989A instru-
/
/
/
D
/
ment in either the electron-impact (EI) or chemical-
ionization (CI) mode. FTIR spectra were determined on
PerkinꢀElmer model 1600 and 2000 FTIR instruments.
/
corresponding deprotected monosaccharides 20ꢀ
/
25.
1H NMR (400 MHz) were determined on GSX FT
NMR spectrometer (JEOL) using TMS as the internal
standard d-values (in ppm) and coupling constants (in
Hz) are given with 0.5 Hz resolution.
The described amino substituted hexo- and heptopy-
ranose derivatives should allow the regio- and stereo-
selective introduction of pharmacophoric substituents
into the pyran moiety (compare lead structure 2) and the
construction of novel morphan analogues (compare lead
structure 3).
3.2. (ꢁ
/
)-1,2:3,4-Di-O-isopropylidene-a-D-galactodialdo-
1,5-pyranose (6)12
A solution of oxalyl chloride (23.6 g, 185.4 mmol) in
THF (15 mL) and CH2Cl2 (20 mL) was cooled to
3. Experimental
ꢃ
/
70 8C. Then, a solution of Me2SO (29.0 g, 370.8
mmol) in CH2Cl2 (20 mL) was slowly added at ꢃ70 8C,
and the mixture was stirred for 10 min at ꢃ70 8C. A
3.1. General methods
/
/
Unless otherwise noted, moisture-sensitive reactions
were conducted under dry nitrogen. Thin-layer chroma-
tography (TLC) was carried out on silica gel 60 F254
plates (E. Merck), and flash chromatography (FC)18 on
solution of 5 (20.0 g, 76.9 mmol) in CH2Cl2 (20 mL) was
added within 5 min, and the mixture was stirred for 10
min at ꢃ
a solution of Et3N (75.0 g, 741.6 mmol) in CH2Cl2 (20
mL) was added within 15 min. After stirring at ꢃ60 8C
/
60 8C. The mixture was cooled to ꢃ70 8C, and
/
silica gel 60, 0.040ꢀ
/
0.063 mm (E. Merck); parentheses
include diameter of the column (cm), eluent, fraction
/
for 30 min, the reaction mixture was warmed to room
temperature (rt) and H2O (100 mL) was added. The
organic layer was separated, and the aqueous layer was
size (mL), and Rf. Melting points (mp) were determined
on a melting point apparatus of Dr Tottoli (Buchi), and
¨
the mps are uncorrected. Optical rotations were mea-
extracted with CH2Cl2 (2ꢄ/100 mL). The organic
sured on a PerkinꢀElmer model 241 spectropolarimeter
/
extracts were dried (Na2SO4), the solvent was evapo-

B. Streicher, B. Wunsch / Carbohydrate Research 338 (2003) 2375ꢀ
/
2385
2379
¨
rated in vacuo, and the residue was purified by FC (8
1.44 (s, 3 H, CH3), 1.65 (s, 3 H, CH3), 3.22ꢀ
/3.29 (m, 2
cm, 70:30 petroleum etherꢀ
Colorless oil, yield 12.9 g (67%), lit.12 82%; [a]D ꢃ
(c 1.13, CHCl3); lit.13 [a]D
1318 (c 0.9, CHCl3).
/
EtOAc, fractions 50 mL).
H, CH2), 4.20 (m, 1 H, 5-H), 4.25 (d, J 8.1 Hz, 1 H, 4-
H), 4.35 (dd, J 5.1/2.2 Hz, 1 H, 2-H), 4.63 (dd, J 8.1/2.2
Hz, 1 H, 3-H), 5.58 (d, J 5.1 Hz, 1 H, 1-H), 8.34 (s,
/
131.38
ꢃ
/
broad, 3 H, NH3ꢂ); EIMS: m/z 260 (Mꢂꢃ
Cl); Anal.
/
3.3. 1,2:3,4-Di-O-isopropylidene-a-
pyranose-6-oxime (7)13
D-galactodialdo-1,5-
Calcd for C12H22ClNO5 (295.8): C, 48.8; H, 7.50; N,
4.73. Found: C, 48.6; H, 7.42; N, 4.45.
A solution of 6 (1.65 g, 6.35 mmol), NH2OH×
/
HCl (1.32
3.5. (ꢁ
isopropylidene-a-
/
)-6-Benzoylamino-6-deoxy-1,2:3,4-di-O-
-galactoyranose (9a)
g, 19.1 mmol), NaOAc (0.825 g, 13.2 mmol) in H2O
(8.25 mL) and CH3OH (80 mL) was stirred at rt for 24
h. The mixture was concentrated in vacuo, and the
D
A solution of 8 (9.31 g, 35.9 mmol), Et3N (4.72 g, 46.7
mmol) and benzoyl chloride (6.56 g, 46.7 mmol) in
CH2Cl2 (50 mL) was stirred for 30 min at rt. The organic
residual aqueous layer was extracted with Et2O (2ꢄ
mL). The concentrated Et2O layer (50 mL) was ex-
tracted with 1 M NaOH (3ꢄ50 mL), then 1 N HCl (pH
4ꢀ5) was added to the NaOH layer, and the aqueous
layer was extracted with Et2O (3ꢄ70 mL). The Et2O
/
60
/
layer was washed with 1 N HCl (3ꢄ
solution of NaHCO3 (3ꢄ50 mL), dried (MgSO4) and
concentrated in vacuo. The residue was purified by FC
(8 cm, 70:30 petroleum etherꢀEtOAc fractions 50 mL,
Rf 0.24). Colorless solid (2-Pr2O), mp 132 8C, yield 9.86
g (76%); [a]D 39.78 (c 1.02, CHCl3); IR (KBr): nꢁ
3354 (NÃH), 1646 (CÄO), 1525 (amide-II), 1254 (CÃO),
1215 (CÃO), 1159 (CÃ O); H NMR
/50 mL), and a satd
/
/
/
layer was dried (MgSO4), concentrated in vacuo and the
residual solid was recrystalized. Colorless solid (2-Pr2O),
/
mp 114ꢀ
/
115 8C, lit.13 mp 107ꢀ
/
108 8C, yield 1.31 g
ꢃ
/
/
(76%), lit.13 66%. The ratio of (E)-7:(Z)-7 varied in
the range from 1:1 to 2:1.
/
/
/
1
/
/
O), 1071 cmꢃ1 (CÃ
/
(CDCl3): d 17 (s, 3 H, CH3), 1.22 (s, 3 H, CH3), 1.33 (s,
3 H, CH3), 1.34 (s, 3 H, CH3), 3.27 (ddd, J 13.9/4.4/3.7
Hz, 1 H, CH2NHCO), 3.83 (ddd, J 13.9/8.1/3.7 Hz, 1 H,
CH2NHCO), 3.89 (ddd, J 8.8/4.4/2.2 Hz, 1 H, 5-H), 4.14
(dd, J 8.1/2.2 Hz, 1 H, 4-H), 4.18 (dd, J 5.1/2.2 Hz, 1 H,
2-H), 4.49 (dd, J 8.1/2.2 Hz, 1 H, 3-H), 5.40 (d, J 5.1 Hz,
1 H, 1-H), 6.47 (t, J 3.7 Hz, 1 H, NH), 7.28 (t, J 7.3 Hz,
3.4. (ꢁ
a-D-galactopyranose (8)
/
)-6-Amino-6-deoxy-1,2:3,4-di-O-isopropylidene-
A mixture of 7 (1.95 g, 7.14 mmol), LiAlH4 (0.74 g, 20
mmol) and Et2O (17 mL) was stirred for 2 h at rt. A
small amount of H2O was carefully added. Then,
MgSO4 was added, the mixture was filtered, and the
filtrate was concentrated in vacuo. The residue was
purified by FC [3 cm, fractions 15 mL, at first the
2 H, H-arom.), 7.33ꢀ
7.3 Hz, 2 H, H-arom.); CIMS: m/z 364 (MHꢂ), 348
(Mꢂꢃ
CH3); Anal. Calcd for C19H25NO6 (363.4): C,
62.8; H, 6.93; N, 3.85. Found: C, 62.7; H, 7.08; N, 3.81.
/7.37 (m, 1 H, H-arom.), 7.61 (d, J
/
solvent was 96:4 CH2Cl2ꢀ
CH2Cl2ꢀCH3OH (200 mL), Rf 0.16 96:4 (CH2Cl2ꢀ
CH3OH). Colorless oil, yield 1.27 g (69%); [a]D
53.18 (c 1.03, CHCl3); IR (film): nꢁ3676 (NH),
3378 (NH), 1383 (CÃN), 1256 (CÃO), 1212 (CÃO),
1168 (CÃ O); H NMR (CDCl3): d
O); 1069 cmꢃ1 (CÃ
/
CH3OH (225 mL)], then 90:10
/
/
3.6. (ꢁ
(phenylacetylamino)-a-D
/
)-6-Deoxy-1,2:3,4-di-O-isopropylidene-6-
-galactopyranose (9b)
ꢃ
/
/
/
/
/
1
/
/
A solution of 8 (0.42 g, 1.62 mmol), Et3N (0.20 g, 1.94
mmol) and phenylacetyl chloride (0.30 g, 1.94 mmol) in
CH2Cl2 (10 mL) was stirred for 30 min at rt. The
1.27 (s, 6 H, CH3), 1.39 (s, 3 H, CH3), 1.47 (s, 3 H, CH3),
1.89 (s, broad, 2 H, NH2), 2.80 (dd, J 13.2/5.1 Hz, 1 H,
CH2NH2), 2.93 (dd, J 13.2/8.1 Hz, 1 H, CH2NH2), 3.67
(ddd, J 8.8/5.1/1.5 Hz, 1 H, 5-H), 4.17 (dd, J 8.1/1.5 Hz,
1 H, 4-H), 4.26 (dd, J 5.1/2.2 Hz, 1 H, 2-H), 4.54 (dd, J
8.1/2.2 Hz, 1 H, 3-H), 5.50 (d, J 5.1 Hz, 1 H, 1-H); 13C
NMR (CDCl3): d 24.29 (CH3), 24.88 (CH3), 25.92
(CH3), 26.01 (CH3), 42.09 (CH2), 69.06 (C-5), 70.32
(C-3), 70.74 (C-4), 71.71 (C-2), 96.33 (C-1), 108.46
[C(CH3)2], 109.19 [C(CH3)2]; CIMS: m/z 260 (MHꢂ),
mixture was washed with 1 N HCl (2ꢄ
satd solution of NaHCO3 (3ꢄ5 mL), dried (MgSO4)
and concentrated in vacuo. The residue was purified by
FC (2 cm, 90:10 petroleum etherꢀEtOAc, Rf 0.06, then
75:25 petroleum etherꢀEtOAc fractions 13ꢀ15 mL, Rf
0.15). Colorless solid (2-Pr2O), mp 72 8C, yield 520 mg
(85%); [a]D 17.28 (c 0.97, CHCl3); IR (KBr): nꢁ3323
(NÃH), 1644 (CÄO), 1556 (amide-II), 1253 (CÃO), 1212
(CÃO), 1167 (CÃ
O), 1069 cmꢃ1 (CÃO); 1H NMR
/5 mL), and a
/
/
/
/
ꢃ
/
/
/
/
/
244 (Mꢂꢃ
/
CH3); Anal. Calcd for C12H21NO5 (259.2):
/
/
/
C, 55.6; H, 8.17; N, 5.40. Found: C, 55.3; H, 8.24; N,
5.38.
(CDCl3): d 1.23 (s, 3 H, CH3), 1.25 (s, 3 H, CH3),
1.32 (s, 3 H, CH3), 1.38 (s, 3 H, CH3), 3.08 (ddd, J 13.2/
Data for 8×
[a]D 50.18 (c 1.06, CH3OH); IR (KBr): nꢁ
(broad, NH3ꢂ), 1599 (NH3ꢂ), 1257 (CÃ
O), 1215 (CÃ
O), 1168 (CÃ
O), 1060 cmꢃ1 (CÃO); 1H NMR
(CD3OD): d 1.32 (s, 3 H, CH3), 1.32 (s, 3 H, CH3),
/
HCl: colorless solid (EtOAc), mp 215 8C;
4.4/3.7 Hz, 1 H, CH2NHCO), 3.49 (s, 2 H, phenylÃ
/
ꢃ
/
/3172
CH2), 3.63 (ddd, J 13.2/8.1/3.7 Hz, 1 H, CH2NHCO),
3.79 (ddd, J 8.1/5.1/1.5 Hz, 1 H, 5-H), 4.07 (dd, J 8.1/1.5
Hz, 1 H, 4-H), 4.20 (dd, J 4.7/2.2 Hz, 1 H, 2-H), 4.49
(dd, J 8.1/2.2 Hz, 1 H, 3-H), 5.38 (d, J 5.1 Hz, 1 H,
/
/
/
/

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/
2385
¨
1-H), 5.80 (t, J 3.7 Hz, 1 H, NH), 7.19ꢀ
/
7.29 (m, 5 H, H-
arom.); CIMS: m/z 378 (MHꢂ), 362 (Mꢂꢃ
CH3); Anal.
Calcd for C20H27NO6 (377.4): C, 63.6; H, 7.21; N, 3.71.
(301.3): C, 55.8; H, 7.69; N, 4.65. Found: C, 55.6; H, 7.9;
N, 4.87.
/
Found: C, 63.7; H, 7.18; N, 3.67.
3.9. (ꢁ
/
)-6-Bromo-6-deoxy-1,2:3,4-di-O-isopropylidene-
a-D-galactopyranose (10a)
3.7. (ꢁ
di-O-isopropylidene-a-
/
)-6-(Benzyloxycarbonylamino)-6-deoxy-1,2:3,4-
Under N2 1,2:3,4-di-O-isopropylidene-a-D-galactopy-
ranose (5) (3.50 g, 11.5 mmol) and CBr4 (3.81 g, 11.5
mmol) were dissolved in CH2Cl2 (15 mL). The solution
D-galactopyranose (9c)
A solution of 8 (1.00 g, 3.86 mmol), Et3N (0.78 g, 7.72
mmol) and benzyl chloroformate (0.99 g, 5.79 mmol) in
CH2Cl2 (20 mL) was stirred for 19 h at rt. The mixture
was cooled to ꢃ
11.5 mmol) in CH2Cl2 (15 mL) was added, and the
mixture was stirred for 2 h at ꢃ60 8C and 24 h at rt. The
solvent was evaporated in vacuo, and the residue was
purified by FC (5 cm, 75:25 petroleum etherꢀEtOAc,
fractions 20 mL, Rf 0.10). Colorless solid, mp 46 8C,
yield 400 mg (11%); [a]D 49.38 (c 1.01, CHCl3); IR
(KBr): nꢁ1255 (CÃO), 1212 (CÃO), 1165 (CÃO), 1070
cmꢃ1 (CÃ
O); H NMR (CDCl3): d 1.34 (s, 3 H, CH3),
1.36 (s, 3 H, CH3), 1.45 (s, 3 H, CH3), 1.55 (s, 3 H, CH3),
3.42 (dd, J 10.3/6.6 Hz, 1 H, ÃCH2Br), 3.52 (dd, J 10.3/
6.6 Hz, 1 H, ÃCH2Br), 3.97 (td, J 6.6/1.5 Hz, 1 H, 5-H),
/
60 8C. Then, a solution of PPh3 (3.01 g,
/
was washed with 1 N HCl (3ꢄ
solution of NaHCO3 (3ꢄ10 mL), dried (MgSO4) and
concentrated in vacuo. The residue was purified by FC
(3 cm, 90:10 petroleum etherꢀEtOAc, Rf 0.21, then
70:30 petroleum etherꢀEtOAc, Rf 0.39 fractions 20
mL). Colorless oil, yield 1.05 g (69%); [a]D 30.38 (c
0.96, CHCl3); IR (film): nꢁ3384 (NÃH), 1723 (CÄ
1526 (amide-II), 1254 (CÃO), 1211 (CÃO), 1071 (CÃ
/10 mL) and a satd
/
/
/
ꢃ
/
/
/
/
/
/
ꢃ
/
1
/
/
/
/O),
/
/
/O),
/
1011 cmꢃ1 (CÃ
/
O); H NMR (CDCl3): d 1.38 (s, 3 H,
1
/
CH3), 1.46 (s, 3 H, CH3), 1.49 (s, 3 H, CH3), 1.52 (s, 3 H,
CH3), 3.37 (ddd, J 12.5/5.9/3.7 Hz, 1 H, CH2NH), 3.56
(ddd, J 12.9/8.1/3.7 Hz, 1 H, CH2NH), 3.97 (ddd, J 7.7/
5.9/1.5 Hz, 1 H, 5-H), 4.25 (dd, J 8.1/1.5 Hz, 1 H, 4-H),
4.35 (dd, J 5.1/2.2 Hz, 1 H, 2-H), 4.65 (dd, J 8.1/2.2 Hz,
4.32 (dd, J 5.1/2.2 Hz, 1 H, 2-H), 4.38 (dd, J 8.1/1.5 Hz,
1 H, 4-H), 4.64 (dd, J 8.1/2.2 Hz, 1 H, 3-H), 5.54 (d, J
5.1 Hz, 1 H, 1-H); 13C NMR (CDCl3): d 24.42 (CH3),
24.86 (CH3), 25.90 (CH3), 25.99 (CH3), 29.69 (CH2Br),
68.37 (C-3), 70.47 (C-4), 70.87 (C-5), 71.00 (C-2), 96.59
(C-1), 108.86 [C(CH3)2], 109.55 [C(CH3)2]; CIMS: m/z
325, 323 (MHꢂ); Anal. Calcd for C12H19BrO5 (323.1):
C, 44.6; H, 5.93. Found: C, 44.8; H, 5.83.
1 H, 3-H), 5.12ꢀ
5.1 Hz, 1 H, 1-H), 7.31ꢀ
z 394 (MHꢂ), 378 (Mꢂꢃ
C20H27NO7 (393.4): C, 61.0; H, 6.92; N, 3.56. Found:
C, 61.2; H, 7.14; N, 3.39.
/
5.19 (m, 3 H, CH2Ph, NH), 5.55 (d, J
7.41 (m, 5 H, arom.); CIMS: m/
CH3); Anal. Calcd for
/
/
3.10. (ꢁ
methylphenylsulfonyl)-a-
/
)-1,2:3,4-Di-O-isopropylidene-6-O-(4-
-galactopyranose (10b)13,15
D
3.8. (ꢁ
/
)-6-(Acetylamino)-6-deoxy-1,2:3,4-di-O-
isopropylidene-a-
D
-galactopyranose (9d)
At 0 8C a solution of 2 (2.00 g, 7.69 mmol) in Py (5 mL)
was added dropwise to a solution of p-TsCl (4.40 g,
23.07 mmol) in Py (5 mL). The reaction mixture was
stirred for 12 h at rt and for 2 h at 60 8C. Then water (20
mL) and Et2O (20 mL) were added, and the aqueous
NaOAc (9.3 mg, 0.11 mmol) and Raney Ni (15.6 mg)
were added to a solution of 7 (90 mg, 0.33 mmol) in
Ac2O (0.25 mL, 0.27 g, 2.01 mmol). The mixture was
hydrogenated with 70 bar of H2 pressure at 80 8C for 16
h. It was filtered, and the filtrate was concentrated in
vacuo. The residue was dissolved in CH2Cl2 (5 mL), and
layer was separated and extracted with Et2O (2ꢄ
mL). The organic layer was dried (MgSO4) and evapo-
rated in vacuo. Colorless solid (2-Pr2O), mp 88ꢀ89 8C,
lit.15 mp 87ꢀ89 8C, yield 3.00 g (94%), lit.15 87%.
/
20
/
the solution was washed with 1 N HCl (3ꢄ
satd solution of NaHCO3 (3ꢄ5 mL), dried (MgSO4)
and concentrated in vacuo. Colorless oil, yield 63 mg
(64%), Rf 0.24 (75:25 petroleum etherꢀEtOAc); [a]D
27.38 (c 1.03, CHCl3); IR (film): nꢁ3318 (NÃH), 1654
(CÄO), 1542 (amide-II), 1256 (CÃO), 1213 (CÃO), 1167
(CÃ
O), 1069 cmꢃ1 (CÃO); 1H NMR (CDCl3): d 1.26 (s,
3 H, CH3), 1.27 (s, 3 H, CH3), 1.38 (s, 3 H, CH3), 1.42 (s,
3 H, CH3), 1.94 (s, 3 H, CH3ÃCÄO), 3.12 (ddd, J 13.9/
/
5 mL) and a
/
/
3.11. (ꢁ
methylsulfonyl)-a-D
/
)-1,2:3,4-Di-O-isopropylidene-6-O-(4-
-galactopyranose (10c)
/
ꢃ
/
/
/
/
/
/
A solution of 2 (2.00 g, 7.69 mmol) in Py (5 mL) was
slowly added at 0 8C to a solution of CH3SO2Cl (1.76 g,
15.4 mmol) in Py (5 mL). After stirring for 12 h at rt,
water (20 mL) and Et2O (20 mL) were added. The
aqueous layer was separated and extracted with Et2O
/
/
/
/
9.5/3.7 Hz, 1 H, CH2), 3.67 (ddd, J 13.9/8.1/3.7 Hz, 1 H,
CH2), 3.83 (ddd, J 9.5/7.3/1.5 Hz, 1 H, 5-H), 4.15 (dd, J
7.7/1.5 Hz, 1 H, 4-H), 4.25 (dd, J 5.1/2.9 Hz, 1 H, 2-H),
4.53 (dd, J 8.1/2.2 Hz, 1 H, 3-H), 5.45 (d, J 5.1 Hz, 1 H,
1-H), 6.08 (t, J 3.7 Hz, 1 H, NH); CIMS: m/z 302
(2ꢄ20 mL). The Et2O layer was dried (MgSO4) and
/
concentrated in vacuo. Colorless solid (2-Pr2O), mp
118 8C, yield 2.10 g (81%), Rf 0.35 (75:25 petroleum
etherꢀ/EtOAc); [a]D
ꢃ
/
117.18 (c 0.99, CHCl3); IR (KBr):
(MHꢂ), 286 (Mꢂꢃ
/CH3); Anal. Calcd for C14H23NO6
nꢁ1348 (RÃ
/
/
SO2OR?), 1239 (CÃ
/
O), 1216 (CÃO), 1174
/

B. Streicher, B. Wunsch / Carbohydrate Research 338 (2003) 2375ꢀ
/
2385
2381
¨
1
(RÃ
/
SO2OR?), 1163 (CÃ
/
O), 1075 cmꢃ1 (CÃ
/
O); 1H NMR
1060 cmꢃ1 (CÃ
CH3), 1.36 (s, 3 H, CH3), 1.48 (s, 3 H, CH3), 3.59 (s, 3ꢄ
0.37 H, OCH3), 3.62 (s, 3ꢄ0.63 H, OCH3), 4.13 (dd, J
/
O); H NMR (CDCl3): d 1.34 (s, 6 H,
(CDCl3): d 1.33 (s, 6 H, CH3), 1.49 (s, 3 H, CH3), 1.58
(s, 3 H, CH3), 3.08 (s, 3 H, ÃOÃSO2ÃCH3), 4.11 (ddd, J
6.6/5.1/1.5 Hz, 1 H, 5-H), 4.24 (dd, J 8.1/1.5 Hz, 1 H, 4-
H), 4.35 (dd, J 5.1/2.6 Hz, 1 H, 2-H), 4.36ꢀ4.40 (m, 2 H,
/
/
/
/
/
8.8/1.5 Hz, 0.37 H, 4-H), 4.19 (dd, J 8.8/1.5 Hz, 1 H, 3-
H), 4.20 (dd, J 8.8/1.5 Hz, 0.63 H, 4-H), 4.29 (dd, J 5.1/
2.2 Hz, 1 H, 2-H), 4.60 (dd, J 8.1/1.5 Hz, 0.37 H, 5-H),
4.66 (dd, J 8.8/5.9 Hz, 0.63 H, (Z)-CH Ä
4.86 (dd, J 8.8/1.5 Hz, 0.63 H, 5-H), 4.97 (dd, J 13.2/8.8
Hz, 0.37 H, (E)-CH ÄCHÃOCH3), 5.54 (d, J 5.1 Hz, 1
H, 1-H), 6.05 (d, J 5.9 Hz, 0.63 H, (Z)-CHÄCH Ã
OCH3), 6.64 (d, J 13.2 Hz, 0.37 H, (E)-CHÄCH Ã
/
Ã
/
CH2Ã
/
OÃ
/
SO2), 4.64 (dd, J 8.1/2.6 Hz, 1 H, 3-H), 5.54
(d, J 5.1 Hz, 1 H, 1-H); 13C NMR (CDCl3): d 24.33
(CH3), 24.84 (CH3), 25.87 (CH3), 25.90 (CH3), 37.86
/
CHÃ/OCH3),
(CH3SO3), 66.28 (C-5), 69.05 (C-3), 69.06 (CH2OSO2Ã
70.34 (C-4), 70.58 (C-2), 96.15 (C-1), 108.99 [C(CH3)2],
109.79 [C(CH3)2]; CIMS: m/z 339 (MHꢂ), 323 (Mꢂꢃ
CH3); Anal. Calcd for C13H22O8S (338.4): C, 46.1; H,
6.55. Found: C, 46.1; H, 6.59.
/),
/
/
/
/
/
/
/
OCH3). The ratio (Z)-12:(E)-12 is 63:37; CIMS: m/z
287 (MHꢂ); Anal. Calcd for C14H22O6 (286.2): C, 58.8;
H, 7.75. Found: C, 58.6; H, 7.87.
3.12. (ꢁ
/
)-6-Cyano-6-deoxy-1,2:3,4-di-O-isopropylidene-
a-D-galactopyranose (11)
3.14. (ꢁ
/
)-6-Deoxy-1,2:3,4-di-O-isopropylidene-a-D-
galacto-heptodialdo-1,5-pyranose (13)
Methanesulfonate 10c (600 mg, 1.77 mmol) was dis-
solved in a solution of LiCN in DMF (1 M, 13 mL) and
heated to 110 8C for 17 h. Then, H2O (5 mL) and
petroleum ether (10 mL) were added, the organic layer
was separated, and the aqueous layer was extracted with
A solution of 12 (100 mg, 0.35 mmol) and 2 N HCl (0.30
mL, ca. 0.60 mmol HCl) in (CH3)2CO (3 mL) was
stirred for 15 min at rt. Then, a solution of Na2CO3 (64
mg, 0.60 mmol) in H2O (5 mL) was added (pH 7) and
petroleum ether (3ꢄ/10 mL). The combined petroleum
the mixture was extracted with Et2O (3ꢄ5 mL). The
/
ether layers were dried (MgSO4), concentrated in vacuo
and the residue (70 mg) was purified by FC (2 cm, 85:15
Et2O layer was dried (MgSO4) and concentrated in
vacuo, and the residue was purified by FC (2 cm, 90:10,
petroleum etherꢀ
Colorless oil, yield 20.2 mg (4.2%); [a]D
CHCl3); IR (film): nꢁ2255 (CN), 1256 (CÃ
(CÃO), 1165 (CÃ
O), 1070 cmꢃ1 (CÃO); 1H NMR
(CDCl3): d 1.27 (s, 3 H, CH3), 1.29 (s, 3 H, CH3),
1.38 (s, 3 H, CH3), 1.47 (s, 3 H, CH3), 2.58 (dd, J 16.9/
7.0 Hz, 1 H, CH2CN), 2.64 (dd, J 16.9/7.0 Hz, 1 H,
CH2CN), 3.98 (t, J 7.0 Hz, 1 H, 5-H), 4.18 (d, J 7.3 Hz,
1 H, 4-H), 4.27 (dd, J 5.1/2.2 Hz, 1 H, 2-H), 4.59 (dd, J
7.3/2.2 Hz, 1 H, 3-H), 5.44 (d, J 5.1 Hz, 1 H, 1-H);
CIMS: m/z 270 (MHꢂ); Anal. Calcd for C13H19NO5
(269.1): C, 58.0; H, 7.12; N, 5.20. Found: C, 58.3; H,
7.18; N, 4.97.
/
EtAOc, fractions 10 mL, Rf 0.38).
52.38 (c 0.57,
O), 1213
petroleum etherꢀ
Colorless oil, yield 90 mg (95%); [a]D
CHCl3); IR (film): nꢁ1727 (CÄO), 1257 (CÃ
(CÃO), 1168 (CÃ
O), 1070 cmꢃ1 (CÃO); 1H NMR
/
EtOAc, fractions 10ꢀ
/
15 mL, Rf 0.16).
64.98 (c 1.01,
O), 1213
ꢃ
/
ꢃ
/
/
/
/
/
/
/
/
/
/
/
/
(CDCl3): d 1.27 (s, 6 H, CH3), 1.39 (s, 3 H, CH3),
1.49 (s, 3 H, CH3), 2.72 (ddd, J 17.4/7.0/1.8 Hz, 1 H,
CH2Ã
/
CHO), 2.64 (ddd, J 17.4/5.9/1.8 Hz, 1 H, CH2Ã
/
CHO), 4.15 (dd, J 8.1/2.2 Hz, 1 H, 4-H), 4.23 (ddd, J
7.0/5.9/2.2 Hz, 1 H, 5-H), 4.26 (dd, J 5.1/2.2 Hz, 1 H, 2-
H), 4.56 (dd, J 8.1/2.2 Hz, 1 H, 3-H), 5.44 (d, J 5.1 Hz, 1
H, 1-H), 9.73 (t, J 1.8 Hz, 1 H, CH2Ã
m/z 257 (Mꢂꢃ
CH3); Anal. Calcd for C13H20O6 (272.2):
C, 57.4; H, 7.41. Found: C, 57.6; H, 7.12.
/
CH Ä/O); CIMS:
/
3.13. (E)- and (Z)-6-Deoxy-1,2:3,4-di-O-isopropylidene-
7-O-methyl-a-
3.15. (ꢁ
galacto-heptopyranose (14)
/
)-6-Deoxy-1,2:3,4-di-O-isopropylidene-a-D-
D
-galacto-hepto-6-enopyranose (12)
At ꢃ
/
78 8C KOtBu (0.90 g, 7.99 mmol) was slowly
NaBH4 (13.9 mg, 0.37 mmol) was carefully added at
0 8C to a solution of 13 (100 mg, 0.37 mmol) in C2H5OH
(7 mL). The mixture was stirred for 4 h at rt. H2O (4
mL) and 2 N HCl (1 mL) were added, the mixture was
concentrated in vacuo, and the residual aqueous layer
added to a solution of (methoxymethyl)triphenylphos-
phonium chloride (2.29 g, 6.66 mmol) in THF (10 mL).
Then a solution of aldehyde 6 (0.86 g, 3.33 mmol) in
Et2O (10 mL) was added dropwise. The mixture was
stirred for 10 min at ꢃ
/
78 8C, then the cooling bath was
was extracted with EtOAc (3ꢄ10 mL). The organic
/
removed, and the mixture was stirred for 5 h at rt.
Subsequently, H2O (10 mL) was added, and the aqueous
extract was dried (MgSO4) and evaporated in vacuo,
and the residue was purified by FC (2 cm, 70:30
layer was separated and extracted with Et2O (3ꢄ
/
20
mL). The organic layer was dried (MgSO4) and con-
petroleum etherꢀ
Colourless oil, yield 63 mg (63%); [a]D
CHCl3); IR (film): nꢁ3448 (OÃH), 1255 (CÃ
(CÃO), 1167 (CÃ
O), 1069 cmꢃ1 (CÃO); 1H NMR
(CDCl3): d 1.34 (s, 3 H, CH3), 1.35 (s, 3 H, CH3),
1.47 (s, 3 H, CH3), 1.54 (s, 3 H, CH3), 1.72ꢀ1.80 (m, 1
/
EtOAc, fractions 30 mL, Rf 0.31).
62.78 (c 0.98,
O), 1212
ꢃ
/
centrated in vacuo, and the residue was purified by FC
/
/
/
(4 cm, 90:10 petroleum etherꢀ
Rf 0.29). Colorless oil, yield 0.60 g (63%); IR (film): nꢁ
1659 (CÄC), 1252 (CÃO), 1213 (CÃO), 1162 (CÃO),
/
EtOAc, fractions 15 mL,
/
/
/
/
/
/
/
/
/

2382
B. Streicher, B. Wunsch / Carbohydrate Research 338 (2003) 2375ꢀ
/
2385
¨
H, CH2CH2OH), 1.93ꢀ
(s, broad, 1 H, OH), 3.75ꢀ
4.01 (ddd, J 8.1/5.9/2.2 Hz, 1 H, 5-H), 4.15 (dd, J 8.1/2.2
Hz, 1 H, 4-H), 4.31 (dd, J 5.1/2.2 Hz, 1 H, 2-H), 4.61
(dd, J 8.1/2.2 Hz, 1 H, 3-H), 5.54 (d, J 5.1 Hz, 1 H, 1-
H); EIMS: m/z 274 (Mꢂ), 259 (Mꢂꢃ
/
2.01 (m, 1 H, CH2CH2OH), 2.09
1 H, 1-H); CIMS: m/z 274 (MHꢂ), 258 (Mꢂꢃ
CH3);
Anal. Calcd for C13H23NO5 (273.3): C, 57.1; H, 8.48; N,
5.12. Found: C, 56.9; H, 8.19; N, 4.84.
/
/3.80 (m, 2 H, CH2CH2OH),
3.18. (ꢁ)-7-(Benzoylamino)-6,7-dideoxy-1,2:3,4-di-O-
-galacto-hepto-pyranose (17a)
/
/CH3); Anal.
isopropylidene-a-D
Calcd for C13H22O6 (274.3): C, 56.9; H, 8.08. Found: C,
56.9; H, 8.09.
Et3N (0.85 g, 8.42 mmol) and benzoyl chloride (1.18 g,
8.42 mmol) were added at 0 8C to a solution of 16 (1.92
g, 7.02 mmol) in CH2Cl2 (20 mL). After stirring for 30
3.16. (E)- and (Z)-6-Deoxy-1,2:3,4-di-O-isopropylidene-
a-
D-galacto-heptodialdo-1,5-pyranose-7-oxime (15)
min at rt, the mixture was washed with 1 N HCl (3ꢄ
/
20
mL) and a saturated solution of NaHCO3 (3ꢄ20 mL).
/
A solution of 13 (240 mg, 0.88 mmol), NH2OH×
/
HCl
The organic layer was dried (MgSO4) and concentrated
in vacuo. Colorless solid (2-Pr2O), mp 120 8C, yield 1.90
(184 mg, 2.65 mmol), NaOAc (145 mg, 1.76 mmol), H2O
(1.6 mL) and CH3OH (16 mL) were stirred for 24 h at rt.
The solvent was evaporated in vacuo. The residue was
g (72%), Rf 0.14 (75:25 petroleum etherꢀ
62.58 (c 1.00, CHCl3); IR (KBr): nꢁ
1639 (CÄO), 1533 (amide-II), 1260 (CÃO), 1212 (CÃ
1166 (CÃ O); H NMR (CDCl3): d
1.37 (s, 3 H, CH3), 1.40 (s, 3 H, CH3), 1.41 (s, 3 H, CH3),
1.52 (s, 3 H, CH3), 1.98ꢀ2.07 (m, 2 H, CH2ÃCH2ÃNH),
3.67ꢀ3.69 (m, 2 H, CH2ÃCH2ÃNH), 3.94 (ddd, J 7.3/
/
EtOAc); [a]D
3369 (NÃH),
O),
ꢃ
/
/
/
dissolved in H2O (5 mL) and extracted with Et2O (2ꢄ
10 mL). The organic layer was dried (MgSO4) and
concentrated in vacuo. Colorless oil, yield 160 mg (63%),
/
/
/
/
1
/
O), 1069 cmꢃ1 (CÃ
/
Rf 0.29 (80:20 petroleum etherꢀ
3412 (OH), 1652 (CÄN), 1256 (CÃ
O); H NMR (CDCl3): d 1.33 (s, 3 H, CH3),
1.35 (s, 3 H, CH3), 1.47 (s, 3 H, CH3), 1.52 (s, 3 H, CH3),
2.54 (m, 1 H, CH2ÃCHÄNOH), 2.69 (m, 1 H, CH2Ã
CHÄNOH), 3.98 (ddd, J 7.3/5.9/2.2 Hz, 1 H, 5-H), 4.17
/
EtOAc); IR (film): nꢁ
/
/
/
/
/
/
O), 1212 (CÃO), 1167
/
/
/
/
1
cmꢃ1 (CÃ
/
4.4/2.2 Hz, 1 H, 5-H), 4.21 (dd, J 8.1/2.2 Hz, 1 H, 4-H),
4.37 (dd, J 5.1/2.2 Hz, 1 H, 2-H), 4.65 (dd, J 8.1/2.2 Hz,
1 H, 3-H), 5.63 (d, J 5.1 Hz, 1 H, 1-H), 6.86 (s, broad, 1
H, NH), 7.47 (t, J 7.3 Hz, 2 H, arom.), 7.53 (t, J 7.0 Hz,
1 H, arom.), 7.84 (d, J 7.3 Hz, 2 H, arom.); EIMS: m/z
/
/
/
/
(dd, J 8.1/2.2 Hz, 1 H, 4-H), 4.32 (dd, J 5.1/2.2 Hz, 1 H,
2-H), 4.62 (dd, J 8.1/2.2 Hz, 1 H, 3-H), 5.52 (d, J 5.1 Hz,
377 (Mꢂ), 362 (Mꢂꢃ
CH3); Anal. Calcd for
/
1 H, 1-H), 6.90 (t, J 5.1 Hz, 0.5 H, CH2Ã
7.51 (t, J 6.2 Hz, 0.5 H, CH2ÃCH ÄNOH). A signal for
the ÄNÃOH proton could not be found; CIMS: m/z 288
(MHꢂ), 272 (Mꢂꢃ
CH3); Anal. Calcd for C13H21NO6
(287.3): C, 54.3; H, 7.37; N, 4.87. Found: C, 54.1; H,
7.59; N, 4.65.
/
CH Ä
/
NOH),
C20H27NO6 (377.4): C, 63.6; H, 7.21; N, 3.71. Found:
C, 63.8; H, 7.23; N, 3.51.
/
/
/
/
/
3.19. (ꢁ)-6,7-Dideoxy-1,2:3,4-di-O-isopropylidene-7-
-galacto-hepto-pyranose (17b)
/
(phenylacetylamino)-a-
D
Et3N (31 mg, 0.31 mmol) and phenylacetyl chloride
(47.5 mg, 0.31 mmol) were added at 0 8C to a solution of
16 (70 mg, 0.26 mmol) in CH2Cl2 (2 mL). After stirring
for 45 min at rt, the mixture was washed with 1 N HCl
3.17. (ꢁ
isopropylidene-a-
/
)-7-Amino-6,7-dideoxy-1,2:3,4-di-O-
D
-galacto-heptopyranose (16)
A solution of 15 (160 mg, 0.56 mmol) in Et2O (1.5 mL)
was slowly added to a suspension of LiAlH4 (42.3 mg,
1.11 mmol) in Et2O (1.5 mL). The suspension was
stirred for 5 h at rt, then a solution of LiAlH4 (1 mL, 1
M in Et2O) was added, and the mixture was stirred for
further 12 h at rt. A small amount of H2O was carefully
added, and the suspension was dried (MgSO4), filtered
and concentrated in vacuo. The residue was purified by
(2ꢄ
/
5 mL) and a satd solution of NaHCO3 (3ꢄ5 mL).
/
The organic extract was dried (MgSO4) and concen-
trated in vacuo. The residue was purified by FC (2 cm,
70:30 petroleum etherꢀ
0.19). Colorless solid (2-Pr2O), mp 62 8C, yield 79.2
mg (79%); [a]D 38.48 (c 1.00, CHCl3); IR (KBr): nꢁ
3339 (NÃH), 1640 (CÄO), 1535 (amide-II), 1261 (CÃO),
1213 (CÃO), 1165 (CÃ O); H NMR
(CDCl3): d 1.24 (s, 3 H, CH3), 1.25 (s, 3 H, CH3), 1.33
(s, 3 H, CH3), 1.38 (s, 3 H, CH3), 1.63ꢀ1.73 (m, 2 H,
CH2ÃCH2ÃNH), 3.17ꢀ3.24 (m, 1 H, CH2ÃCH2ÃNH),
3.37ꢀ3.42 (m, 1 H, CH2ÃCH2ÃNH), 3.49 (s, 2 H,
phenylÃCH2), 3.65 (ddd, J 6.6/4.6/2.2 Hz, 1 H, 5-H),
/EtOAc, fractions 15 mL, Rf
ꢃ
/
/
/
/
/
1
/
/
O), 1070 cmꢃ1 (CÃ
/
FC (2 cm, 96:4, CH2Cl2ꢀ
0.19). Colorless oil, yield 70 mg (46%); [a]D
1.02, CHCl3); IR (film): nꢁ3462 (NH), 3369 (NH),
/CH3OH, fractions 7 mL, Rf
ꢃ
/
48.48 (c
/
/
/
/
/
/
/
1
1289 (CÃ
/
N), 1231 (CÃ
/
O), 1099 cmꢃ1 (CÃ
/
O); H NMR
/
/
/
(CDCl3): d 1.30 (s, 3 H, CH3), 1.33 (s, 3 H, CH3), 1.46
(s, 3 H, CH3), 1.49 (s, broad, 2 H, NH2), 1.52 (s, 3 H,
/
3.99 (dd, J 8.1/2.2 Hz, 1 H, 4-H), 4.19 (dd, J 5.1/2.2 Hz,
CH3), 1.60ꢀ
(m, 1 H, CH2Ã
CH2ÃNH2), 3.87 (ddd, J 7.3/5.9/1.5 Hz, 1 H, 5-H), 4.12
/
1.67 (m, 1 H, CH2Ã
/
CH2Ã
/
NH2), 1.82ꢀ1.88
/
1 H, 2-H), 4.48 (dd, J 8.1/2.2 Hz, 1 H, 3-H), 5.29 (d, J
/
CH2ÃNH2), 2.83ꢀ
/
/
2.89 (m, 2 H, CH2Ã
/
5.1 Hz, 1 H, 1-H), 5.91 (s broad, 1 H, NH), 7.20ꢀ
/
7.30
(m, 5 H, arom.); CIMS: m/z 392 (MHꢂ), 376 (Mꢂꢃ
/
/
(dd, J 8.1/2.2 Hz, 1 H, 4-H), 4.30 (dd, J 5.1/2.2 Hz, 1 H,
CH3); Anal. Calcd for C21H29NO6 (391.5): C, 64.4; H,
7.47; N, 3.58. Found: C, 64.6; H, 7.54; N, 3.39.
2-H), 4.59 (dd, J 8.1/2.2 Hz, 1 H, 3-H), 5.53 (d, J 5.1 Hz,

B. Streicher, B. Wunsch / Carbohydrate Research 338 (2003) 2375ꢀ
/
2385
2383
¨
3.20. (ꢁ
/
)-7-(Benzyloxycarbonylamino)-6,7-dideoxy-
4.50 (t, J 4.8 Hz, 1 H, 2-H), 4.64 (dd, J 6.9/4.4 Hz, 1 H,
4-H), 4.88 (dt, J 8.1/5.5 Hz, 1 H, 5-H), 5.58 (d, J 5.1 Hz,
1 H, 1-H), 5.79 (t, J 4.4 Hz, 1 H, 3-H), 6.62 (d, J 4.4 Hz,
1,2:3,4-di-O-isopropylidene-a-D-galacto-hepto-pyranose
(17c)
1 H, 7-H1), 7.39ꢀ
H, arom.), 7.96 (dd, J 8.1/1.5 Hz, 2 H, arom.), 8.05 (dd,
J 7.3/1.5 Hz, 2 H, arom.); EIMS: m/z 319 [Mꢂꢃ
PhCO2]; Anal. Calcd for C24H24O8 (440.5): C, 65.4; H,
5.49. Found: C, 65.3; H, 5.60.
Data for 19b (Rf 0.15): colorless solid (2-Pr2O), mp
/
7.45 (m, 4 H, arom.), 7.52ꢀ
/
7.95 (m, 2
Et3N (340 mg, 3.36 mmol) and benzyl chloroformate
(287 mg, 1.68 mmol) were added at 0 8C to a solution of
16 (460 mg, 1.68 mmol) in CH2Cl2 (10 mL). After
stirring for 16 h at rt, the mixture was washed with 1 N
/
HCl (3ꢄ
10 mL). The organic extract was dried (MgSO4) and
concentrated in vacuo. Colorless solid (1:1 hexaneꢀ2-
Pr2O), mp 94 8C, yield 534 mg (78%), Rf 0.22 (80:20
petroleum etherꢀEtOAc); [a]D 28.68 (c 1.00, CHCl3);
IR (KBr): nꢁ3357 (NH), 1716 (CÄO), 1533 (amide-II),
1255 (CÃO), 1211 (CÃO), 1167 (CÃ
O), 1071 cmꢃ1 (CÃ
O); 1H NMR (CDCl3): d 1.32 (s, 3 H, CH3), 1.35 (s, 3 H,
CH3), 1.46 (s, 3 H, CH3), 1.59 (s, 3 H, CH3), 1.80ꢀ1.91
(m, 2 H, CH2ÃCH2ÃNH), 3.30ꢀ3.50 (m, 2 H, CH2Ã
CH2ÃNH), 3.81ꢀ3.84 (m, 1 H, 5-H), 4.12 (dd, J 6.6/
2.2 Hz, 1 H, 4-H), 4.31 (dd, J 5.1/2.2 Hz, 1 H, 2-H), 4.59
(dd, J 8.1/2.2 Hz, 1 H, 3-H), 5.09ꢀ5.13 (m, 3 H, CH2Ph,
7.53 (m, 5 H,
/
10 mL) and a satd solution of NaHCO3 (3ꢄ
/
155 8C, yield 92.8 mg (47%); [a]D
CHCl3); IR (KBr): nꢁ1732 (CÄO), 1276 (CÃ
(CÃ
O), 1076 cmꢃ1 (CÃO); 1H NMR (CDCl3): d 1.38 (s,
ꢂ
/
16.68 (c 0.25,
/
/
/
/
O), 1120
/
/
/
ꢃ
/
3 H, CH3exo), 1.62 (s, 3 H, CH3endo), 2.45 (d, J 15.4 Hz,
1 H, 6-H), 2.61 (dt, J 15.4/5.9 Hz, 1 H, 6-H), 4.47 (t, J
4.4 Hz, 1 H, 2-H), 4.55 (t, J 5.9 Hz, 1 H, 4-H), 4.67 (t, J
5.9 Hz, 1 H, 5-H), 5.77 (d, J 5.1 Hz, 1 H, 1-H), 5.91 (dd,
J 6.6/4.4 Hz, 1 H, 3-H), 6.48 (d, J 5.9 Hz, 1 H, 7-H),
/
/
/
/
/
/
/
/
/
/
/
6.94 (t, J 7.3 Hz, 2 H, arom.), 7.22ꢀ7.27 (m, 3 H,
/
/
/
arom.), 7.47 (dd, J 7.3/1.5 Hz, 1 H, arom.), 7.73 (dd, J
7.3/1.5 Hz, 2 H, arom.), 7.86 (dd, J 6.6/1.5 Hz, 2 H,
arom.); 13C NMR (CDCl3): d 25.17 (CH3exo), 25.96
(CH3endo), 38.89 (C-6), 64.60 (C-3), 68.51 (C-5), 72.32
(C-2), 77.58 (C-4), 97.01 (C-1), 98.95 (C-7), 110.14
/
NH), 5.53 (d, J 5.1 Hz, 1 H, 1-H), 7.30ꢀ
/
arom.); CIMS: m/z 408 (MHꢂ); Anal. Calcd for
C21H29NO7 (407.5): C, 61.9; H, 7.17; N, 3.44. Found:
C, 61.7; H, 7.30; N, 3.47.
[C(CH3)2], 127.86 (2ꢄ
arom.), 128.95 (C-arom.), 129.69 (4ꢄ
129.83 (C-arom.), 132.70 (C-arom.), 132.81 (C-arom.),
165.70 (2ꢄ CÄO). The signals were assigned by a
1H,13C HETCOR spectrum; EIMS: m/z 319 [Mꢂꢃ
/
C-arom.), 128.06 (2ꢄ
/
C-
/
C-arom.),
3.21. (ꢂ
isopropylidene-a-
4,7-furanose (19a) and (ꢂ
deoxy-1,2-O-isopropylidene-a-
1,5-pyranose-4,7-furanose (19b)
/
)-(7R)-3,7-di-O-Benzoyl-6-deoxy-1,2-O-
-galacto-heptodialdo-1,5-pyranose-
)-(7S)-3,7-di-O-benzoyl-6-
-galacto-heptodialdo-
/
/
D
/
/
PhCO2]; Anal. Calcd for C24H24O8 (440.5): C, 65.4; H,
5.49. Found: C, 65.4; H, 5.58.
D
A solution of 12 (200 mg, 0.70 mmol) and 2 N H2SO4
(0.30 mL) in (CH3)2CO (6 mL) was heated to reflux for
75 min. The solution was neutralized with 2 N NaOH
(0.3 mL) and concentrated in vacuo. The residue was
3.22. 6-(Benzoylamino)-6-deoxy-a- and b-D-
galactopyranose (20a and 21a)
purified by FC (2 cm, 96:4 CH2Cl2ꢀCH3OH, fractions
30 mL) to yield 18a and 18b colorless oils, yield 57 mg
(35%).
Et3N (0.46 g, 4.5 mmol), benzoyl chloride (0.56 g, 4.0
mmol) and DMAP (100 mg, 0.8 mmol) were added at
0 8C to a solution of 18a/18b (105 mg, 0.45 mmol,
/
A mixture of 9a (40 mg, 0.11 mmol), a strong acidic ion-
exchange resin (40 mg), (CH3)2CO (7 mL) and H2O (1
mL) was heated to reflux for 25 h. Then the mixture was
filtered, the solvent was evaporated in vacuo, and the
residue was purified by FC (2 cm, 80:20 CH2Cl2ꢀ
CH3OH, fractions 10 mL, Rf 0.49). Colorless oil, yield
24.7 mg (79%); IR (film): nꢁ3363 (OÃH, NÃH), 1634
O), 1546 cmꢃ1 (amide-II); H NMR (CD3OD): d
3.35ꢀ3.76 (m, 5 H, 3-H, 4-H, 5-H, 6-H), 4.10 [t, J 6.6
/
18a:18bꢁ
rt, the mixture was extracted with 1 N HCl (2ꢄ
and a satd solution of NaHCO3 (2ꢄ10 mL). The
/1:2) CH2Cl2 (10 mL). After stirring for 48 h at
/
/
/
/10 mL)
1
(CÄ
/
/
/
organic layer was dried (MgSO4) and concentrated in
vacuo, and the residue was purified by FC (2 cm, 85:15
Hz, 0.5 H, 2-H (21a)], 4.33 [td, J 7.3/4.4 Hz, 0.5 H, 2-H
(20a)], 5.05 [d, J 3.7 Hz, 0.5 H, 1-H (20a)], 7.35 (t, J 7.3
Hz, 2 H, arom.), 7.43 (td, J 7.3/1.5 Hz, 1 H, arom.), 7.73
(dd, J 7.3/1.5 Hz, 2 H, arom.). The signal of H-1 of the
anomer 21a was hidden under the HCD2OD signal
petroleum etherꢀ
and 8 contained the isomer 19a, and fractions 13ꢀ
contained the isomer 19b.
Data for 19a (Rf 0.35): colorless solid (2-Pr2O), mp
144 8C, yield 47.4 mg (24%); [a]D 18.08 (c 0.25,
CHCl3); IR (KBr): nꢁ1725 (CÄO), 1268 (CÃO), 1114
(CÃ
O), 1078 cmꢃ1 (CÃO); 1H NMR (CDCl3): d 1.38 (s,
/EtOAc, fractions 20 mL). Fractions 7
/21
(4.70ꢀ4.85 ppm) of the solvent. The signals of the OH-
/
ꢂ
/
and NH-protons are not seen in the solvent CD3OD.
The ratio of anomers 20a:21a is 1:1; EIMS: m/z 266
/
/
/
/
/
(Mꢂꢃ
55.1; H, 6.05; N, 4.94. Found: C, 54.9; H, 6.09; N, 5.09.
/OH); Anal. Calcd for C13H17NO6 (283.3): C,
3 H, CH3exo), 1.58 (s, 3 H, CH3endo), 2.47 (dt, J 14.7/5.1
Hz, 1 H, 6-H), 2.63 (ddd, J 14.7/8.1/1.5 Hz, 1 H, 6-H),

2384
B. Streicher, B. Wunsch / Carbohydrate Research 338 (2003) 2375ꢀ
/
2385
¨
3.23. (ꢁ
galactopyranoside (20c) (ꢁ
deoxy-b- -galactopyranoside (21c), and ethyl 6-
/
)-Ethyl 6-(benzoylamino)-6-deoxy-a-
D
-
3.31 (ddd, J 13.9/9.5/4.4 Hz, 1 H, 7-H), 3.40 (s, 3 H,
/
)-ethyl 6-(benzoylamino)-6-
OCH3), 3.82ꢀ/3.85 (m, 1 H, 5-H), 3.96 (d, J 11.0 Hz, 1
D
H, 2-H), 4.01ꢀ/4.07 (m, 3 H, 7-H, 3-H, 4-H), 4.88 (d, J
(benzoylamino)-6-deoxy-a- and b-
(22c)
D-galactofuranoside
11.0 Hz, 1 H, 1-H), 4.94 (s, broad, 1 H, OH), 5.70 (s,
broad, 1 H, OH), 6.51 (t, J 5.5 Hz, 1 H, NH), 7.47 (t, J
8.1 Hz, 2 H, arom.), 7.52ꢀ7.58 (m, 1 H, arom.), 7.77 (dd,
/
A mixture of 9a (40 mg, 0.11 mmol), a strong acidic ion-
exchange resin (40 mg) and C2H5OH (8 mL) was heated
to reflux for 69 h. Then, the mixture was filtered and
concentrated in vacuo, and the residue was purified by
J 8.8/1.5 Hz, 2 H, arom.); the signals were assigned by a
1H,13C COSY spectrum; CIMS: m/z 312 (MHꢂ), 280
(Mꢂꢃ
CH3O); Anal. Calcd for C15H21NO6 (311.3): C,
57.9; H, 6.80; N, 4.50. Found: C, 57.6; H, 7.04; N, 4.39.
/
FC (2 cm, 98:2 EtOAcꢀ
Data for 20c (Rf 0.24): colorless oil, yield 8.1 mg
(24%); [a]D 23.98 (c 0.34, CHCl3); IR (film): nꢁ3356
(OÃH, NÃH), 1644 (CÄ
/
CH3OH, fractions 10 mL).
Data for 25b (Rf 0.14): colorless oil, yield 89.3 mg
(68%); IR (film): nꢁ
(amide-II), 1075 (CÃ
O), 1040 cmꢃ1 (CÃ
(CD3OD): d 1.78ꢀ1.96 (m, 2 H, 6-H), 3.26 (s, 3ꢄ
H, OCH3), 3.35ꢀ3.38 (m, 2ꢄ0.65 H, 7-H), 3.40 (s, 3ꢄ
0.35 H, OCH3), 3.44ꢀ3.50 (m, 0.65 H, 4-H, 3ꢄ
7-H, 4-H), 3.57ꢀ3.68 (m, 0.35 H, 5-H), 3.74ꢀ
2ꢄ0.65 H, 2-H, 3-H, 2ꢄ
4.4 Hz, 0.65 H, 5-H), 4.02 (d, J 7.3 Hz, 0.35 H, 1-H),
4.59 (d, J 2.9 Hz, 0.65 H, 1-H), 7.33ꢀ7.37 (m, 2 H,
arom.), 7.41ꢀ7.43 (m, 1 H, arom.), 7.70ꢀ7.73 (m, 2 H,
/
3344 (OÃ
/
H), 1640 (CÄ
/
O), 1544
1
ꢃ
/
/
/
/
O); H NMR
1
/
/
/
O), 1544 cmꢃ1 (amide-II); H
/
/0.65
NMR (CDCl3): d 1.25 (t, J 7.0 Hz, 3 H, OCH2CH3),
/
/
/
3.43 (s, broad, 1 H, OH), 3.56 (dq, J 16.2/7.0 Hz, 1 H,
/
/0.35 H,
OCH2CH3), 3.74ꢀ
/
3.89 (m, 4 H, OCH2CH3, 5-H, 6-H),
/
/
3.77 (m,
4.07ꢀ4.16 (m, 4 H, 2-H, 3-H, 4-H, OH), 4.96 (s, broad, 1
/
/
/0.35 H, 2-H, 3-H), 3.75 (q, J
H, OH), 5.09 (s, 1 H, 1-H), 7.03 (s, broad, 1 H, NH),
7.47 (t, J 7.7 Hz, 2 H, arom.), 7.56 (t, J 7.3 Hz, 1 H,
arom.), 7.81 (d, J 6.6 Hz, 2 H, arom.); CIMS: m/z 312
/
/
/
(MHꢂ), 266 (Mꢂꢃ
/C2H5O); Anal. Calcd for
arom.), the signals of the OH- and NH-protons were not
observed in the solvent, CD3OD. The signals were
C15H21NO6 (311.3): C, 57.9; H, 6.80; N, 4.50. Found:
C, 57.6; H, 7.05; N, 4.46.
1
assigned by a H,1H COSY spectrum. The ratio of the
Data for 21c and 22c (Rf 0.19): fractions 8ꢀ
contained an inseparable mixture of 21c:22c in a ratio
of 18:82. Colorless oil, yield 12.9 mg (38%).
/
15
a- and b-anomers a-25b:b-25b was 65:35; 13C NMR
(CD3OD): d 31.37 (C-6), 31.75 (C-6), 37.97 (C-7), 38.21
(C-7), 55.73 (OCH3), 57.25 (OCH3), 69.46 (C-5), 70.05
(C-5), 71.49 (C-4), 72.21 (C-4), 72.41 (C-3), 72.74 (C-3),
73.96 (C-2), 75.01 (C-2), 101.54 (C-1), 105.82 (C-1),
128.2 (C-arom.), 129.5 (C-arom.), 132.6 (C-arom.),
3.24. (ꢁ
galacto-heptopyranoside (23b), (ꢂ
(benzoylamino)-6,7-dideoxy-b- -galacto-heptopyranoside
(24b), and methyl 7-(benzylamino)-6,7-dideoxy-a- and b-
-galacto-heptofuranoside (25b)
/
)-Methyl 7-(benzoylamino)-6,7-dideoxy-a-
D-
/)-methyl 7-
D
135.7 (C-arom.), 170.3 (CÄ
by a 1H,13C HETCOR spectrum; EIMS: m/z 311 (Mꢂ),
280 (Mꢂꢃ
CH3O); Anal. Calcd for C15H21NO6 (311.3):
/O); the signals were assigned
D
/
C, 57.9; H, 6.80; N, 4.50. Found: C, 57.7; H, 7.05; N,
4.74.
A mixture of 17a (160 mg, 0.42 mmol), a strong acidic
ion-exchange resin (60 mg) and CH3OH (8 mL) was
heated to reflux for 48 h. Then the mixture was filtered
and concentrated in vacuo, and the residue was purified
3.25. (ꢁ
galacto-heptopyranoside (23c), ethyl 7-(benzoylamino)-
6,7-dideoxy-b- -galacto-heptopyranoside (24c), and ethyl
/
)-Ethyl 7-(benzoylamino)-6,7-dideoxy-a-D-
by FC (2 cm, 90:10 CH2Cl2ꢀ
Data for 23b (Rf 0.27): colorless oil, yield 26.1 mg
(20%); [a]D 10.88 (c 0.46, CHCl3); IR (film): nꢁ3333
(OÃH, NÃH), 1637 (CÄ
O), 1545 (amide-II), 1023 cmꢃ1
(CÃO); H NMR (CDCl3): d 1.76ꢀ1.90 (m, 2 H, 6-H),
3.05 (s, broad, 1 H, OH), 3.49 (s, 3 H, OCH3), 3.51ꢀ3.56
(m, 1 H, 7-H), 3.76ꢀ3.84 (m, 5 H, 2-H, 3-H, 5-H, 2ꢄ
OH), 4.08ꢀ4.13 (m, 2 H, 7-H, 4-H), 4.85 (d, J 2.2 Hz, 1
H, 1-H), 6.88 (s, broad, 1 H, NH), 7.42ꢀ7.45 (m, 2 H,
arom.), 7.47ꢀ7.56 (m, 1 H, arom.), 7.77 (dd, J 8.8/1.5
Hz, 2 H, arom.); CIMS: m/z 312 (MHꢂ), 280 (Mꢂꢃ
/CH3OH, fractions 10 mL).
D
7-(benzylamino)-6,7-dideoxy-a- and b-D-galacto-
heptofuranoside (25c)
ꢃ
/
/
/
/
/
1
/
/
A mixture of 17a (40 mg, 0.11 mmol), a strong acidic
ion-exchange resin (40 mg) and C2H5OH (8 mL) was
heated to reflux for 70 h. Then the mixture was filtered
and concentrated in vacuo, and the residue was purified
/
/
/
/
/
by FC (2 cm, at first 96:4 CH2Cl2ꢀ
mL) then EtOAc (200 mL), fractions 15 mL.
Data for 23c (Rf 0.29 90:10 CH2Cl2ꢀCH3OH): color-
less oil, yield 8.8 mg (26%); [a]D ꢃ16.68 (c 0.26, CHCl3);
IR (film): nꢁ3362 (OÃH), 1634 (CÄ
O), 1538 cmꢃ1
(amide-II); H NMR (CDCl3): d 1.20 (t, J 7.0 Hz, 3 H,
OCH2CH3), 1.64ꢀ1.70 (m, 1 H, 6-H), 2.03ꢀ2.11 (m, 1
H, 6-H), 3.04 (s, broad, 1 H, OH), 3.29ꢀ3.37 (m, 1 H, 7-
H), 3.52 (dq, J 16.9/7.3 Hz, 1 H, OCH2CH3), 3.74ꢀ3.85
(m, 2 H, OCH2CH3, 5-H), 3.96ꢀ4.06 (m, 4 H, 2-H, 3-H,
/
CH3OH) (ca. 100
/
/
/
CH3O); Anal. Calcd for C15H21NO6 (311.3): C, 57.9; H,
6.80; N, 4.50. Found: C, 57.6; H, 7.12; N, 4.45.
Data for 24b (Rf 0.20): colorless oil, yield 6.5 mg
/
/
/
/
1
(4.9%); [a]D
(OÃH), 1641 (CÄ
O); 1H NMR (CDCl3): d 1.60ꢀ
2.14 (m, 1 H, 6-H), 2.88 [d, J 11.7 Hz, 1 H, OH (C-4)],
ꢂ
/
86.78 (c 0.21, CHCl3); IR (film): nꢁ
O), 1551 (amide-II), 1029 cmꢃ1 (CÃ
1.71 (m, 1 H, 6-H), 2.06ꢀ
/
3351
/
/
/
/
/
/
/
/
/
/

B. Streicher, B. Wunsch / Carbohydrate Research 338 (2003) 2375ꢀ
/
2385
2385
¨
4. Nakahara, Y.; Beppu, K.; Ogawa, T. Tetrahedron Lett.
1981, 22, 3197ꢀ3200.
5. Kanai, K.; Sakamoti, I.; Ogawa, S.; Suami, T. Bull. Chem.
Soc. Jpn. 1987, 60, 1529ꢀ1531.
6. Jones, K.; Wood, W. W. Carbohydr. Res. 1986, 155, 217ꢀ
4-H, 7-H, CH2N), 4.95 (s, broad, 1 H, OH), 5.04 (s, 1 H,
1-H), 5.59 (s, broad, 1 H, OH), 6.61 (s, broad, 1 H, NH),
7.46 (t, J 7.3 Hz, 2 H, arom.), 7.54 (t, J 7.3 Hz, 1 H,
arom.), 7.76 (dd, J 8.8/1.5 Hz, 2 H, arom.); CIMS: m/z
/
/
326 (MHꢂ), 280 (Mꢂꢃ
C2H5O); Anal. Calcd for
/
/
222.
7. Dziewiszek, K.; Zamojski, A. Carbohydr. Res. 1986, 150,
C16H23NO6 (325.4): C, 59.1; H, 7.13; N, 4.30. Found:
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Data for 24c and 25c (Rf 0.24, 90:10 CH2Cl2ꢀ
/
CH3OH): fractions 9ꢀ25 contained an inseparable
/
/
mixture of 24c:25c in a ratio of 10:90. Colorless oil,
yield 25.4 mg (74%).
/
¨
120.
10. Hofner, G.; Streicher, B.; Wunsch, B. Arch. Pharm.
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Financial support of this work by the Deutsche For-
schungsgemeinschaft and the Fonds der Chemischen
Industrie is gratefully acknowledged. Thanks are also
due to the Degussa AG for donation of chemicals.
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