Highly stereoselective synthesis of 2-amino-3-c-methyl-2,3-dideoxyaldoses by C3-chain elongation via homoaldol reaction of sugar aldehydes

Article abstract of DOI:10.1055/S-0029-1218628

A flexible strategy for the stereoselective synthesis of branched amino sugar analogues is described. It is based on a C₃-chain elongation of suitable protected aldoses. By using the sequence homoaldol reaction, epoxidation, and methanolysis α-methyl allo-furanosides are obtained. Proximate amination of the corresponding triflates afford the title compounds. All reactions proceed with high yield, high diastereoselectivities, and allow for a broad application. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/S-0029-1218628

PAPER
749
Highly Stereoselective Synthesis of 2-Amino-3-C-methyl-2,3-dideoxyaldoses
by C3-Chain Elongation via Homoaldol Reaction of Sugar Aldehydes
Stereoselectiv
a
e
S
ynthesis
b
of 2-Amino
i
3-
C
-m
n
ethyl-2,3-did
e
eoxyaldoses Kollmann, Roland Fröhlich, Dieter Hoppe*
Westfälische Wilhelms-Universität Münster, Organisch-Chemisches Institut, Corrensstr. 40, 48149 Münster, Germany
Fax +49(251)8336531; E-mail: dhoppe@uni-muenster.de
Received 11 September 2009; revised 16 November 2009
Dedicated to Professor Günter Haufe on the occasion of his 60th birthday
13
Epoxidation using tert-butyl hydroperoxide/VO(acac)2
Abstract: A flexible strategy for the stereoselective synthesis of
branched amino sugar analogues is described. It is based on a C3-
chain elongation of suitable protected aldoses. By using the se-
quence homoaldol reaction, epoxidation, and methanolysis a-meth-
led to diastereomerically pure oxiranes 7,12 which upon
methanolysis afforded the a-methyl allo-furanosides 8
(Scheme 2, Table 1).12,14,15 The 1,2-cis,2,3-cis,3,4-trans
yl allo-furanosides are obtained. Proximate amination of the configuration of the furanosides was confirmed by an X-
ray crystal structure analysis of 8c (Figure 1).16–24
corresponding triflates afford the title compounds. All reactions
proceed with high yield, high diastereoselectivities, and allow for a
broad application.
The stereochemistry of the protected aminofuranosides 11
was proved by NOE experiment of compound 11c and
Key words: homoaldol reaction, stereoselective synthesis, furano-
sides, aminoaldoses, carbamates
confirmed
(Figure 2).
the
2,3-trans,3,4-trans
configuration
The furanosides 8 were quantitatively transformed into
triflates 925 by reaction with an excess of triflic anhydride,
and the crude triflates were directly treated with excess of
sodium azide to yield the azidodeoxyfuranosides 10 with
clean inversion at C-2.26 The yields given for the azides 10
in Table 2 refer to two steps, the triflate and azide forma-
tion. The 2,3-trans configuration of 10 was concluded
Modified carbohydrates often have interesting biological
properties.2 They play an important role in the synthesis of
antibiotics,3 enzymes,4 and biological active natural prod-
ucts.5 In particular, aminodeoxy sugars are valuable tar-
gets.6 2-Amino-2,3-dideoxy-3-C-methylaldoses 1, to the
best of our knowledge, have not been reported yet.7 Here-
in we describe a flexible synthesis of compounds 1
(Scheme 1), based on a C3-chain elongation of suitable
protected aldoses 3 by utilization of the homoaldol reac-
tion,8 which has been developed in our group.9
3
from the small coupling constants J2,3 of 1.5–2.4 Hz in
1
the H NMR spectra. Subsequent hydrogenolysis (H2,
H
Ti(OiPr)3
a
b
H
+ R*CH=O (3a–e)
OCb
OCb
(S)-4
5
OH OH
OH NHR
OH
OH
O
H
H
R*
R*
c
R*
R*
O
O
1
2
OCb
OCb
6
7
Ti(OiPr)3
OH
O
d
O
O
N
R*
OMe
R*
H
O
OCb
8
3
O
O
O
H
O
4
O
O
O
O
R* =
Scheme 1 General synthesis of compounds 1
O
O
O
c
b
a
O
Addition of the homoenolate reagent (S)-4,10 prepared
from (E)-but-2-enyl N,N-diisopropylcarbamate (5), to the
protected aldoses 3a–e11 afforded the 4-hydroxyenol car-
bamates 6 in diastereomerically pure, highly enantioen-
riched form (≥98% ee) (Scheme 2, Table 1).12
O
MeO
O
O
OBn
d
e
O
O
Scheme 2 Synthesis of furanosides 8 by homoaldol reaction, epoxi-
dation, and methanolysis. Reagents and conditions: a) n-BuLi, (–)-
sparteine, n-pentane–cyclohexane (6.7:1), –78 °C, 3.5 h, Ti(Oi-Pr)4,
–78 °C, 40 min; b) R*CHO, –78 °C, 4 h; c) t-BuOOH, VO(acac)2,
CH2Cl2, r.t., 15 h; d) MeSO3H, MeOH, CH2Cl2, –78 °C, 15 h.
SYNTHESIS 2010, No. 5, pp 0749–0756
Advanced online publication: 04.01.2010
DOI: 10.1055/s-0029-1218628; Art ID: T18109SS
© Georg Thieme Verlag Stuttgart · New York
x
x
.
x
x
.2
0
1
0

750
S. Kollmann et al.
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Table 1 Synthesis of Furanosides 8 by Homoaldol Reaction, Subsequent Epoxidation, and Methanolysis
Protected aldose 3 Carbamate 6a (Yield)
Epoxide 7a (Yield)
Furanoside 8a (Yield)
OH
OH
OH
O
2
6
6
4
5
3
5
7
3
5
3
4
1
4
2
3a
6
1
O
O
O
2
OMe
O
H
O
O
OCb
OCb
O
8ab (85%)
6ab (55%)
7ab (90%)
OH
OH
H
OH
H
O
O
O
7
O
2
4
3
O
O
O
O
3
3
4
H
1
6
2
6
4
5
7
8
7
5
5
3b
1
8
9
OMe
2
6
O
H
8
O
O
OCb
OCb
9
9
10
O
8bb (81%)
O
O
7bb (70%)
6bb (72%)
O
O
O
10
9
9
OH
O
O
OH
O
OH
O
8
7
8
9
7
3
H 4
O
O
5
O
6
2
5
3
3
4
1
4
7
2
3c
5
OMe
2
O
O
O
6
1
8
O
O
O
6
O
OCb
OCb
8c (76%)
O
H
O
O
6cb (50%)
7cb (75%)
OH
3
OH
4
OH
4
O
4
5
2
H
H
O
O
3
3
8
O
1
2
1
8
MeO
9
MeO
5
5
MeO
2
OMe
6
3d
3e
O
6
6
H
OCb
OCb
7
7
8
7
8d (73%)
O
O
O
O
O
O
7d (85%)
6d (50%)
OH
3
O
OH
O
OH
O
4
2
O
6
5
H
7
O
3
4
6
O
O
1
5
3
6
4
2
8
7
1
OMe
5
2
9
8
8
7
O
O
OCb
O
OCb
6e (63%)
8e (69%)
O
7e (70%)
a Numbering of compounds 6a–e, 7a–e, and 8a–e is for the assignment of the 1H and 13C NMR data.
b For data and characterization, see ref. 12.
Boc
H
H
O
H
N
H
O
H
O
O
OMe
O
O
Figure 2 NOE experiment of 11c
Pd/C) followed by acylation with Boc2O gave rise to pro-
tected aminofuranosides 11 (Scheme 3, Table 2).27
The method outlined above gives facile access to chain
elongated 2-amino-2,3-dideoxy-3-C-methylaldoses 11
via nucleophilic introduction of the terminal C1–C3 to
sugar aldehydes, having D-arabinose configuration at C2–
C4 in compounds 10 and 11. The absolute configuration
at C2– C4 is determined by the R- or S-configuration of
the applied homoenolate reagent;12 the configuration at
C5 to Cw of the applied sugar aldehyde is retained. The
prepared furanosides correspond to the following amino
Figure 1 Crystal structure of 8c
Synthesis 2010, No. 5, 749–756 © Thieme Stuttgart · New York

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Stereoselective Synthesis of 2-Amino-3-C-methyl-2,3-dideoxyaldoses
751
Table 2 Azidolysis, Hydrogenolysis, and Substitution of Furanosides 8
Furanoside 8
Triflate 9a
Azide 10 a (Yield)
Boc-protected amine 11a (Yield)
O
N3
OSO2CF3
HN
3
4
5
4
5
3
7
OtBu
OMe
7
H
H
4
5
3
7
8a
H
6
6
6
O
OMe
O
OMe
2
2
O
O
O
2
O
O
O
9a
O
10a (80%)
11a (70%)
O
OSO2CF3
N3
HN
O
O
O
4
OtBu
O
4
3
4
3
O
3
O
H 5
H 5
H5
7
7
7
8b
8c
8
9
8
9
8
9
OMe
OMe
2
2
OMe
6
6
2
6
O
O
O
H
H
H
10
10
10
O
O
O
O
O
O
9b
10b (70%)
11b (70%)
O
O
O
O
N3
OSO2CF3
3
HN
10
O
3
10
O
4
4
3
H
10
O
H 4
H
9
OtBu
9
O
O
6
7
O
O
9
8
O
OMe
OMe
2
5
O
2
5
O
O
6
O
O
OMe
2
5
O
8
8
6
7
O
7
9c
11c (62%)
O
O
10c (61%)
O
O
N3
OSO2CF3
HN
3
3
4
4
3
4
H5
H 5
OtBu
OMe
O
O
9
H
9
MeO
MeO
O
5
9
OMe
MeO
OMe
2
2
6
7
6
7
8d
8e
O
O
2
6
7
H
O
8
H
8
H
8
9d
10d (73%)
O
O
O
O
11d (65%)
O
O
OSO2CF3
3
N3
O
4
O
3
H 4
7
7 H
6
O
O
OMe
6
5
2
OMe
5
2
O
O
9
8
9
8
O
O
10e (69%)
9e
a Numbering of compounds 9a–e, 10a–e, and 11a–d is for the assignment of the 1H and 13C NMR data.
The C-3 substituent of the title compounds can be
changed by utilization of the appropriate homoenolates, in
which the g-methyl group is exchanged by another resi-
due, and also the C2–C4 L-arabinose series is accessible
by using the O’Brien28 diamine [a good (+)-sparteine
mimic] in the deprotonation step of the homoaldol reac-
tion. Taking also in consideration the great versatility in
the aldehyde (or ketone) unit a vast variety of amino sug-
ars is accessible.
OH
OSO2CF3
OMe
a
R
OMe
R
O
O
8
9
O
HN
OtBu
N3
b
c
R
OMe
R
OMe
O
O
11
10
All moisture-sensitive reactions were carried out under an atmo-
sphere of argon in flame-dried glassware sealed by rubber septa.
Unless otherwise specified, materials were obtained from commer-
cial sources and used without purification. All solvents (n-pentane,
Et2O, CH2Cl2) were dried according to standard procedures and pu-
rified by distillation prior to use. Addition of chemicals was per-
formed by using disposable plastic syringes. Flash chromatography
was performed using Merck silica gel 60 (230–400 mesh) at a pres-
sure of about 1.5 bar and monitored by TLC. Solvents for chroma-
tography (Et2O, n-pentane, cyclohexane, EtOAc) were distilled
prior to use. For analytic TLC, Merck aluminum sheets (60 F254 sil-
ica gel) were used. Visualization was accomplished with permanga-
Scheme 3 Synthesis of 2-aminofuranosides 11 by amination.
Reagents and conditions: a) (CF3SO2)2O, pyridine, -15 °C → –5 °C,
3 h, b) NaN3, DMSO, 50 °C, 5–15 h; c) Boc2O, Pd/C, H2, THF, r.t.,
9 h.
sugars: 11a: 2-amino-2,3-dideoxy-3-C-methyl-D-altro-
hexose; 11b: 2-amino-2,3-dideoxy-3-C-methyl-L-lyxo-L-
galacto-nonodialdose; 11c: 2-amino-2,3-dideoxy-3-C-
methyl-L-threo-L-galacto-1-aldo-5-ulose; 11d: 2-amino-
2,3-dideoxy-3-C-methyl-L-erythro-L-galacto-octodiald-
ose; 10e: 3-azido-2,3-dideoxy-3-C-methyl-D-glycero-D-
altro-aldoheptose.
1
nate solution and vanillin solution. H and 13C NMR spectra were
recorded on a Bruker ARX 300 or ARX 400 spectrometer. Chemi-
Synthesis 2010, No. 5, 749–756 © Thieme Stuttgart · New York

752
S. Kollmann et al.
PAPER
cal shifts are given in ppm (d), with TMS (1H) and CDCl3 (13C) as
internal standard. The multiplicities are indicated by s (singlet), br s
(broad singlet), d (doublet), br d (broad doublet), t (triplet), q (quar-
tet), and m (multiplet). The numbering of the compounds may differ
from the IUPAC nomenclature and is defined in Tables 1 and 2. Op-
tical rotations were measured at 20 °C using a Perkin-Elmer 341
spectrometer; the ATR-IR spectra were recorded using a Varian
3100 Excalibur series spectrometer. Elemental analyses were per-
formed at the Department of Organic Chemistry of the University
of Münster. ESI-MS (HR-MS) was carried out with a Quattro LCZ
(Waters-Micromass, Manchester, UK) with nanospray inlet.
IR (ATR): 3488, 2971, 2934, 2873, 1684, 1440, 1368, 1289, 1134,
1057, 762 cm–1.
3
1H NMR (400 MHz, CDCl3): d = 1.12 [d, J (3,3-CH3) = 7.1 Hz,
3 H, 3-CH3], 1.23 (br s, 12 H, 2¢-CH3), 1.29, 1.34 [s each, 6 H,
C(CH3)2], 3.08 (d, 3J4,4-OH = 2.7 Hz, 1 H, 4-OH), 3.02–3.15 (m, 1 H,
3-H), 3.39–3.55 (m, 2 H, 6-H, 7-HA), 3.63–3.74 (m, 2 H, 5-H, 7-
3
HB), 3.78, 4.14 (br s each, 2 H, 1¢-H), 4.06 (ddd, J3,4 = 4.7 Hz,
2
3J4,5 = 7.4 Hz, 1 H, 4-H), 4.59 (d, J8A,8B = 2.7 Hz, 2 H, 8-CH2),
3
3
4.82 (d, J1,2 = 6.6 Hz, J2,3 = 10.3 Hz, 1 H, 2-H), 7.10 (dd,
4J1,3 = 0.6 Hz, 1 H, 1-H), 7.26–7.39 (m, 5 H, C6H5).
13C NMR (100 MHz, CDCl3): d = 17.8 (3-CH3), 20.2 (C-2¢), 26.7,
26.9 [C(CH3)2], 32.9 (C-3), 45.4, 46.9 (C-1¢), 70.7 (C-7), 73.7 (C-
8), 75.9 (C-6), 78.2 (C-4), 80.9 (C-5), 108.9 [C(CH3)2], 110.7 (C-2),
128.5, 128.0, 127.9 (CHAr), 135.5 (C-1), 137.0 (CAr), 153.1
(NC=O).
4-Hydroxyalk-1-enyl Carbamates 6a–e; General Procedure
In a three-necked, round-bottomed flask equipped with a cooled
dropping funnel and a mechanical stirrer, (E)-crotyl carbamate 5
(1.0 equiv) and (–)-sparteine (12; 1.1 equiv) were dissolved in a
mixture of n-pentane–cyclohexane (6.7:1, 1.5 mL/mmol) and
cooled to –78 °C. To this solution was added a solution of 1.6 M n-
BuLi in n-hexane (1.1 equiv) dropwise. The mixture was stirred for
3.5 h and a solution of Ti(Oi-Pr)4 (3.0 equiv) in n-pentane (1 mL/
mmol), precooled to –78 °C, was added. After a transmetalation
time of 40 min, a solution of the aldehyde 3a, 3b, 3c, 3d, or 3e
(1.1 equiv) in n-pentane (0.5 mL/mmol) was added at –78 °C, and
the stirring was continued for an additional 3 h. The reaction was
stopped by the addition of sat. aq NH4Cl (1 mL/mmol) at –78 °C,
warmed to r.t., and washed with sat K/Na tartrate solution (10 mL/
mmol). The aqueous layer was separated and extracted with Et2O (3
× 10 mL/mmol). The combined organic phases were dried
(Na2SO4), the solvent was evaporated, and the residue was purified
by column chromatography on silica gel (Et2O–n-pentane, 1:2 →
2:1).
Anal. Calcd for C25H39NO6: C, 66.79; H, 8.74; N, 3.12. Found: C,
66.66; H, 9.00; N, 2.98.
1,2-Epoxy-4-hydroxyalkyl Carbamates 7a–e; General Proce-
dure
Homoaldol adduct 6 (1.0 equiv) was dissolved in CH2Cl2 (3 mL/
mmol) under argon. VO(acac)2 (2 mol%, 0.05 mmol) and t-BuOOH
(3.0 equiv) were added at r.t. and the reaction mixture was allowed
to stir for 15 h. The reaction was stopped by the addition of Me2S
(3.0 equiv) and the mixture was stirred for an additional 30 min.
The mixture was extracted with sat. aq NaHCO3 (7 mL/mmol) and
the combined organic extracts were dried (MgSO4). The solvent
was evaporated and the crude product was purified by flash column
chromatography on silica gel (Et2O–n-pentane, 1:1 → 2:1).
The experimental data and characterization of epoxides 7a–c are al-
ready published.12
The experimental data and characterization of 4-hydroxyalk-1-enyl
carbamates 6a–c are already published.12
[3R,4S,4(2R,3R,4R,5R)]-1,2-Epoxy-4-(2,3,4-trihydroxy-3,4-O-
isopropylidene-5-O-methyl-2-tetrahydrofuranyl)-4-hydroxy-3-
methylbutyl N,N-Diisopropylcarbamate (7d)
[Z,3S,4S,4(2R,3R,4R,5R)]-4-Hydroxy-4-(2,3,4-trihydroxy-3,4-
O-isopropylidene-5-O-methyl-2-tetrahydrofuranyl)-3-methyl-
but-1-enyl N,N-Diisopropylcarbamate (6d)
According to the General Procedure, the reaction of 5 (2.99 g,
15.0 mmol) with aldehyde 3d (3.35 g, 16.5 mmol) gave 3.01 g
(7.5 mmol, 50%) of 6d as a colorless solid; mp 94.2 °C; Rf = 0.23
(Et2O–n-pentane, 1:1); [a]D20 –59.5 (c 0.75, CHCl3).
According to the General Procedure, 6d (0.79 g, 1.9 mmol) was
converted with VO(acac)2 (11.0 mg, 0.04 mmol) and t-BuOOH
(0.36 mL, 2.9 mmol) into the product 7d (0.70 g, 1.67 mmol, 85%)
20
as a colorless oil; Rf = 0.28 (Et2O–n-pentane, 3:1); [a]D –36.8 (c
1.36, CHCl3).
IR (ATR): 3467, 2971, 2937, 2877, 1700, 1442, 1439, 1373, 1290,
1193, 1060, 762 cm–1.
IR (ATR): 3471, 2972, 2936, 1702, 1529, 1435, 1371, 1210, 1046,
897, 762 cm–1.
3
1H NMR (400 MHz, CDCl3): d = 1.10 [d, J (3,3-CH3) = 7.0 Hz,
3
1H NMR (400 MHz, CDCl3): d = 1.12 [d, J (3,3-CH3) = 7.2 Hz,
3
3 H, 3-CH3], 1.23 (br s, 12 H, 2¢-CH3), 1.27, 1.43 [s each, 6 H,
C(CH3)2], 2.95 (m, 1 H, 3-H), 3.19 (s, 1 H, 4-OH), 3.38 (s, 3 H,
OCH3), 3.52 (m, 1 H, 4-H), 3.91, 3.99 (br s each, 2 H, 1¢-H), 4.28
3 H, 3-CH3], 1.22 (d, J1¢,2¢ = 6.9 Hz, 12 H, 2¢-CH3), 1.32, 1.48 [s
each, 6 H, C(CH3)2], 1.64 (s, 1 H, 4-OH), 1.98 (m, 1 H, 3-H), 3.08
3
3
(dd, J1,2 = 2.8 Hz, J2,3 = 9.1 Hz, 1 H, 2-H), 3.44 (s, 3 H, OCH3),
3.74 (m, 1 H, 4-H), 3.79, 4.00 (br s each, 2 H, 1¢-H) 3.82 (d,
3J6,7 = 2.4 Hz, 1 H, 6-H), 4.48 (d, 3J7,8 = 2.4 Hz, 1 H, 7-H), 4.59 (d,
3J4,5 = 6.1 Hz 1 H, 5-H), 4.97 (s, 1 H, 8-H), 5.69 (d, 3J1,2 = 2.8 Hz,
1 H, 1-H).
3
3
(br d, J4,5 = 3.5 Hz, 1 H, 5-H), 4.52 (dd, J5,6 = 5.5 Hz,
3J6,7 = 6.1 Hz, 1 H, 6-H), 4.72 (d, 3J1,2 = 6.5 Hz, 3J2,3 = 9.8 Hz, 1 H,
2-H), 4.90 (d, 3J6,7 = 6.1 Hz, 1 H, 7-H), 4.91 (s, 1 H, 8-H), 7.10 (dd,
4J1,3 = 0.9 Hz, 1 H, 1-H).
13C NMR (100 MHz, CDCl3): d = 17.9 (3-CH3), 20.3 (C-2¢), 24.6,
26.3 [C(CH3)2], 32.8 (C-3), 45.8, 46.5 (C-1¢), 55.3 (OCH3), 75.9 (C-
4), 80.4 (C-6), 85.7 (C-5), 90.0 (C-7), 109.7 (C-8), 111.9 [C(CH3)2],
112.4 (C-2), 135.6 (C-1), 152.5 (NC=O).
13C NMR (100 MHz, CDCl3): d = 13.6 (3-CH3), 21.2, 21.4 (C-2¢),
24.7, 26.3 [C(CH3)2], 35.9 (C-3), 45.8, 46.6 (C-1¢), 55.5 (OCH3)
56.6 (C-2), 75.1 (C-1), 76.2 (C-4), 80.4 (C-6), 85.8 (C-5), 90.4 (C-
7), 110.0 (C-8), 111.9 [C(CH3)2], 153.8 (NC=O).
Anal. Calcd for C20H35NO7: C, 59.83; H, 8.79; N, 3.49. Found: C,
59.50; H, 8.71; N, 3.30.
Anal. Calcd for C20H35NO8: C, 57.54; H, 8.45; N, 3.35. Found: C,
57.18; H, 8.24; N 2.96.
[Z,3S,4S,4(5R,6S)]-7-O-Benzyl-4,5,6,7-tetrahydroxy-5,6-O-iso-
propylidene-3-methylhept-1-enyl N,N-Diisopropylcarbamate
(6e)
[3R,4S,4(5R,6S)]-7-O-Benzyl-1,2-epoxy-4,5,6,7-tetrahydroxy-
5,6-O-isopropylidene-3-methylheptyl N,N-Diisopropylcarba-
mate (7e)
According to the General Procedure, the reaction of 5 (1.97 g,
10.0 mmol) with aldehyde 3e (2.77 g, 11.0 mmol) gave 2.76 g
(6.3 mmol, 63%) of 6e as a colorless oil; Rf = 0.27 (Et2O–n-pentane,
1:1); [a]D20 –76.0 (c 0.78, CHCl3).
According to the General Procedure, 6e (0.45 g, 1.0 mmol) was
converted with VO(acac)2 (6.4 mg, 0.03 mmol) and t-BuOOH
(0.5 mL, 3.1 mmol) into the product 7e (0.32 g, 0.7 mmol, 70%) as
Synthesis 2010, No. 5, 749–756 © Thieme Stuttgart · New York

PAPER
Stereoselective Synthesis of 2-Amino-3-C-methyl-2,3-dideoxyaldoses
753
20
a colorless oil; Rf = 0.37 (Et2O–n-pentane, 1:1); [a]D20 +4.9 (c 1.05,
CHCl3).
as a colorless oil; Rf = 0.32 (Et2O–n-pentane, 3:1); [a]D –73.7 (c
0.65, CHCl3).
IR (ATR): 3453, 2972, 2934, 2876, 1701, 1500, 1434, 1370, 1212,
1047, 896, 699 cm–1.
IR (ATR): 3496, 2982, 2937, 2836, 1701, 1456, 1414, 1373, 1210,
1193, 1088, 1035, 948 cm–1.
3
3
1H NMR (400 MHz, CDCl3): d = 1.11 [d, J (3,3-CH3) = 7.4 Hz,
1H NMR (300 MHz, CDCl3): d = 1.11 [d, J (4,4-CH3) = 7.2 Hz,
3
3 H, 3-CH3], 1.22 (d, J1¢,2¢ = 6.8 Hz, 12 H, 2¢-CH3), 1.34, 1.35 [s
3 H, 4-CH3], 1.31, 1.47 [s each, 6 H, C(CH3)2], 2.22 (m, 1 H, 4-H),
each, 6 H, C(CH3)2], 2.10 (ddq, 3J2,3 = 9.5 Hz, 3J3,4 = 2.6 Hz, 1 H, 3-
H), 3.16 (dd, 3J1,2 = 2.8 Hz, 1 H, 2-H), 3.51–3.59, 3.68–3.81, 3.97–
4.05 (m each, 6 H, OH, 4-H, 5-H, 6-H, 7-HA, 7-HB), 3.71, 4.11 (br
s each, 2 H, 1¢-H), 4.59, 4.61 (s each, 2 H, 8-HA, 8-HB), 5.66 (d,
3J1,2 = 2.8 Hz, 1 H, 1-H), 7.29–7.38 (m, 5 H, C6H5).
2.49 (d, 3J3,3-OH = 8.6 Hz, 1 H, 3-OH), 3.34, 3.43 (s each, 3 H each,
OCH3) 3.67 (dd, 3J4,5 = 5.3 Hz, J5,6 = 9.5 Hz, 1 H, 5-H), 3.93 (dd,
3
3J6,7 = 1.3 Hz, 1 H, 6-H), 4.20 (m, 1 H, 3-H), 4.55 (dd,
3J7,8 = 6.1 Hz, J8,9 = 10.5 Hz, 1 H, 8-H), 4.83 (dd, J6,7 = 1.3 Hz,
3
3
1 H, 7-H), 4.89 (d, 3J2,3 = 4.5 Hz, 1 H, 2-H), 4.95 (s, 1 H, 9-H).
13C NMR (100 MHz, CDCl3): d = 15.3 (3-CH3), 20.8 (C-2¢), 26.7,
26.8 [C(CH3)2], 35.2 (C-3), 46.8 (C-1¢), 56.6 (C-2), 70.6 (C-7), 73.9
(C-4), 74.9 (C-8), 75.7 (C-6), 78.7 (C-1), 81.1 (C-5), 108.9
[C(CH3)2], 128.6, 128.0 (CHAr), 136.8 (CAr), 154.4 (NC=O).
13C NMR (75 MHz, CDCl3): d = 12.9 (4-CH3), 25.0, 26.5
[C(CH3)2], 38.9 (C-4), 55.4, 55.5 (OCH3), 73.0 (C-3), 81.9 (C-6),
83.7 (C-8), 85.1 (C-5), 89.5 (C-7), 103.1 (C-2), 109.6 [C(CH3)2],
112.4 (C-9).
Anal. Calcd for C25H39NO7: C, 64.49; H, 8.44; N, 3.01. Found: C,
64.42; H, 8.79; N 2.94.
Anal. Calcd for C14H24O7: C, 55.25; H, 7.95. Found: C, 55.60; H,
8.02.
g-Lactol Methyl Ethers 8a–e; General Procedure
[2S,3R,4S,5S,5(2R,3S)]-5-(3-O-Benzyl-1,2,3-trihydroxy-1,2-O-
isopropylidene)-2-methoxy-4-methyltetrahydrofuran-3-ol (8e)
According to the General Procedure, 7e (0.32 g, 0.7 mmol) was
converted with MeOH (0.04 mL, 51.8 mmol) and methanesulfonic
acid (0.05 mL, 0.6 mmol) into the product 8e (0.17 g, 0.48 mmol,
1,2-Epoxy-4-hydroxyalkyl carbamate 7 (1.0 equiv) and MeOH
(74 equiv) were dissolved in CH2Cl2 (2 mL/mmol) under argon.
The reaction mixture was cooled to –78 °C and was treated with
MeSO3H (0.9 equiv). The mixture was stirred for 15 h at –78 °C,
the reaction stopped by the addition of NaH2PO4/Na2HPO4 buffer
(20 mL/mmol), and diluted with Et2O (10 mL/mmol). The organic
layer was washed with brine (20 mL/mmol) and dried (MgSO4).
The solvent was evaporated and the crude product was purified by
flash column chromatography on silica gel (Et2O–n-pentane, 1:2 →
2:1).
20
69%) as a colorless oil; Rf = 0.45 (Et2O–n-pentane, 2:1); [a]D
+56.4 (c 0.53, CHCl3).
IR (ATR): 3528, 2985, 2933, 2878, 1715, 1454, 1411, 1370, 1249,
1214, 1094, 1067, 1010 cm–1.
3
1H NMR (400 MHz, CDCl3): d = 1.09 [d, J (4,4-CH3) = 7.2 Hz,
3 H, 4-CH3], 1.41, 1.42 [s each, 6 H, C(CH3)2], 2.21 (m, 1 H, 4-H),
The experimental data and characterization for tetrahydrofurans 8a
and 8b are already published.12
3
2.44 (d, J3,OH = 8.2 Hz, 1 H, OH), 3.41 (s, 3 H, OCH3), 3.58 (dd,
3J7,8A = 6.0 Hz, 2J8A,8B = 10.3 Hz, 1 H, 8-HA), 3.67 (dd,
3J7,8B = 3.6 Hz, 1 H, 8-HB), 3.76–3.85 (m, 2 H, 5-H, 6-H), 4.05 –
4.11 (m, 1 H, 7-H), 4.16 (ddd, 3J2,3 = 4.4 Hz, 3J3,4 = 3.7 Hz, 1 H, 3-
[2S,3R,4S,5S,5(2S,3S,4R,5S)]-5-(2,3,4-Trihydroxy-5-hydroxy-
methyl-2,3;4,5¢-di-O-isopropylidene-2-tetrahydrofuranyl)-2-
methoxy-4-methyltetrahydrofuran-3-ol (8c)
According to the General Procedure, 7c (0.64 g, 1.3 mmol) was
converted with MeOH (4.05 mL, 100.0 mmol) and MeSO3H
(0.08 mL, 1.2 mmol) into the product 8c (0.37 g, 1.03 mmol, 76%)
as a colorless solid; mp 110.5 °C; Rf = 0.28 (Et2O–n-pentane, 1:1);
[a]D20 –66.9 (c 0.52, CHCl3).
3
H), 4.61 (s, 2 H, 9-CH2), 4.84 (d, J2,3 = 4.4 Hz, 1 H, 2-H), 7.27–
7.36 (m, 5 H, C6H5).
13C NMR (100 MHz, CDCl3): d = 12.8 (4-CH3), 27.0, 27.1
[C(CH3)2], 37.8 (C-4), 55.5 (OCH3), 70.8 (C-6), 73.1 (C-8), 73.4
(C-9), 78.6 (C-3) 79.6 (C-7), 84.7 (C-5), 103.3 (C-2), 109.8
[C(CH3)2], 128.3, 127.6 (CHAr), 138.2 (CAr).
Anal. Calcd for C19H28O6: C, 64.75; H, 8.01. Found: C, 65.15; H,
8.27.
IR (ATR): 3515, 2995, 2932, 2832, 1451, 1386, 1369, 1283, 1249,
1200, 1144, 1088, 1076, 1003, 833 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.16 [d, J (3,3-CH3) = 7.1 Hz,
3
Azido Deoxyfuranosides 10a–e; General Procedure
3 H, 4-CH3], 1.35, 1.41, 1.42, 1.48 [s each, 12 H, C(CH3)2], 2.49 (d,
Preparation of Triflates 9: A solution of furanoside 8 (1.0 equiv) in
pyridine (5 mL/mmol) at –15 °C was treated with Tf2O (2.0 equiv).
The mixture was allowed to stir for 3 h at -5 °C. The reaction was
stopped by the addition of aq NH4Cl (10 mL/mmol), and warmed to
r.t. The organic layer was separated and the aqueous layer was ex-
tracted with Et2O (10 mL/mmol) and the combined organic extracts
were washed with aq NH4Cl (10 mL/mmol), aq NaHCO3 (10 mL/
mmol), and brine (10 mL/mmol), and dried (Na2SO4). The solvent
was evaporated and the crude product 9 was used without further
purification.
3
3
3J4,OH = 7.5 Hz, 1 H, OH), 2.54 (ddq, J3,4 = 7.6 Hz, J4,5 = 6.6 Hz,
1 H, 4-H), 3.48 (s, 3 H, OCH3), 3.99–4.10 (m, 4 H, 5-H, 9-H, 10-
3
HA, 10-HB), 4.21 (ddd, J2,3 = 2.5 Hz, 1 H, 3-H), 4.22 (d,
3
3J8,9 = 2.5 Hz, 1 H, 8-H), 4.40 (br s, 1 H, 7-H), 4.97 (d, J2,3 = 2.5
Hz, 1 H, 2-H).
13C NMR (100 MHz, CDCl3): d = 12.8 (4-CH3), 18.8, 26.8, 27.8,
28.6 [C(CH3)2], 36.4 (C-4), 55.8 (OCH3), 60.2 (C-10), 72.0 (C-8),
73.3 (C-3), 73.7 (C-9), 84.5 (C-5), 85.2 (C-7), 103.6 (C-2), 97.2,
111.9 [C(CH3)2], 116.1 (C-6).
Anal. Calcd for C17H28O8: C, 56.65; H, 7.83. Found: C, 56.54; H,
7.75.
Conversion of Triflates 9 into Azides 10: Triflates 9 and NaN3
(5 equiv) were dissolved in DMSO (5 mL/mmol) and the mixture
was warmed to 50 °C (5–15 h). The mixture was cooled to r.t. and
the reaction was stopped by the addition of H2O (3 mL/mmol). The
organic layer was separated and the aqueous layer was extracted
with Et2O (10 mL/mmol). The combined organic layers were
washed with brine (10 mL/mmol) and dried (Na2SO4). The solvent
was evaporated and the residue was purified by column chromatog-
raphy on silica gel (Et2O–n-pentane, 1:3 → 2:1).
[2S,3R,4S,5S,5(2R,3R,4R,5R)]-5-(2,3,4-Trihydroxy-3,4-O-iso-
propylidene-5-O-methyl--2-tetrahydrofuranyl)-2-methoxy-4-
methyltetrahydrofuran-3-ol (8d)
According to the General Procedure, 7d (0.35 g, 0.8 mmol) was
converted with MeOH (2.50 mL, 61.4 mmol) and MeSO3H
(0.05 mL, 0.8 mmol) into the product 8d (0.18 g, 0.61 mmol, 73%)
Synthesis 2010, No. 5, 749–756 © Thieme Stuttgart · New York

754
S. Kollmann et al.
PAPER
[2S,3S,4S,5S,5(1R)]-3-Azido-5-(1,2-dihydroxy-1,2-O-isopropy-
lideneethyl)-2-methoxy-4-methyltetrahydrofuran (10a)
13C NMR (75 MHz, CDCl3): d = 17.5 (4-CH3), 18.7, 26.8, 27.9,
28.6 [C(CH3)2], 40.1 (C-4), 55.2 (OCH3), 60.1 (C-10), 71.9 (C-8),
72.8 (C-3), 73.7 (C-9), 83.3 (C-5), 86.4 (C-7), 107.1 (C-2), 97.4,
112.0 [C(CH3)2], 116.0 (C-6).
According to the General Procedure, the reaction of furanoside 8a
(0.07 g, 0.3 mmol) with Tf2O (0.15 g, 0.5 mmol) in pyridine fol-
lowed by the treatment of triflate 9a with NaN3 (48.8 mg,
0.8 mmol) gave 61.7 mg (0.24 mmol, 80%) of 10a as a colorless oil;
Rf = 0.57 (Et2O–n-pentane, 1:1); [a]D20 +60.0 (c 1.08, CHCl3).
Anal. Calcd for C17H27N3O7: C, 52.98; H, 7.06; N,10.90. Found: C,
53.04; H, 7.15; N, 10.65.
IR (ATR): 2988, 2935, 2835, 2098, 1457, 1371, 1253, 1215, 1105,
1065, 1025 cm–1.
[2S,3S,4S,5S,5(2R,3R,4R,5R)]-3-Azido-5-(2,3,4-trihydroxy-3,4-
O-isopropylidene-5-O-methyl-2-tetrahydrofuranyl)-2-meth-
oxy-4-methyltetrahydrofuran (10d)
According to the General Procedure, the reaction of furanoside 8d
(0.18 g, 0.6 mmol) with Tf2O (0.30 g, 1.1 mmol) in pyridine fol-
lowed by the treatment of triflate 9d with NaN3 (0.12 g, 2.8 mmol)
gave 0.14 g (0.44 mmol, 73%) of 10d as a colorless resin; Rf = 0.68
(Et2O–n-pentane, 1:1); [a]D20 –58.2 (c 0.53, CHCl3).
3
1H NMR (300 MHz, CDCl3): d = 1.25 [d, J (4,4-CH3) = 7.1 Hz,
3 H, 4-CH3], 1.35, 1.43 [s each, 6 H, C(CH3)2], 2.13 (ddq,
3
3J3,4 = 6.1 Hz, J4,5 = 4.8 Hz, 1 H, 4-H), 3.35 (s, 3 H, OCH3), 3.52
3
(dd, J5,6 = 1.6 Hz, 1 H, 5-H), 3.57–3.68 (m, 1 H, 6-H), 3.86–4.17
3
(m, 2 H, 7-HA, 7-HB), 4.09 (dd, J2,3 = 1.6 Hz, 1 H, 3-H), 4.82 (d,
3J2,3 = 1.6 Hz, 1 H, 2-H).
IR (ATR): 2981, 2930, 2837, 2099, 1455, 1372, 1254, 1210, 1091,
1074, 1023 cm–1.
13C NMR (75 MHz, CDCl3): d = 17.4 (4-CH3), 25.2, 26.7
[C(CH3)2], 43.0 (C-4), 55.1 (OCH3), 67.3 (C-7), 73.0 (C-3), 77.7
(C-6), 84.8 (C-5), 107.5 (C-2), 109.5 [C(CH3)2].
3
1H NMR (400 MHz, CDCl3): d = 1.26 [d, J (4,4-CH3) = 6.9 Hz,
3 H, 4-CH3], 1.33, 1.49 [s each, 6 H, C(CH3)2], 2.15 (m, 1 H, 4-H),
Anal. Calcd for C11H9N3O4: C, 51.35; H, 7.44; N, 16.33. Found: C,
51.61; H, 7.56; N, 16.04.
3
3.35, 3.36 (s each, 3 H each, OCH3), 3.59 (dd, J2,3 = 1.5 Hz,
3
3
3J3,4 = 4.4 Hz, 1 H, 3-H), 3.67 (dd, J4,5 = 6.4 Hz, J5,6 = 9.2 Hz,
3
1 H, 5-H), 4.10 (dd, J6,7 = 1.3 Hz 1 H, 6-H), 4.57 (dd,
[2S,3S,4S,5S,5(2R,3S,4S,5R,6R)]-3-Azido-5-(3,4,5,6-tetrahy-
droxy-3,4;5,6-di-O-isopropylidene-2-tetrahydropyranyl)-2-
methoxy-4-methyltetrahydrofuran (10b)
According to the General Procedure, the reaction of furanoside 8b
(0.16 g, 0.4 mmol) with Tf2O (0.23 g, 0.8 mmol) in pyridine fol-
lowed by the treatment of triflate 9b with NaN3 (61.0 mg,
0.1 mmol) gave 0.12 g (0.31 mmol, 70%) of 10b as a colorless oil;
Rf = 0.60 (Et2O–n-pentane, 1:1); [a]D20 –10.3 (c 0.85, CHCl3).
3J7,8 = 6.1 Hz, 3J8,9 = 10.1 Hz, 1 H, 8-H), 4.84–4.89 (m, 2 H, 2-H, 7-
H), 4.97 (s, 1 H, 9-H).
13C NMR (100 MHz, CDCl3): d = 17.4 (4-CH3), 25.0, 26.6
[C(CH3)2], 43.2 (C-4), 55.2, 55.4 (OCH3), 73.0 (C-3), 82.0 (C-6),
84.3 (C-8), 85.1 (C-5), 89.3 (C-7), 107.8 (C-2), 110.0 [C(CH3)2],
112.5 (C-9).
HRMS-ESI (EM): m/z calcd for [C14H23N3O6 + Na]+: 352.1479;
IR (ATR): 2999, 2927, 2855, 2103, 1458, 1381, 1255, 1211, 1103,
1067, 1001 cm–1.
found: 352.1477.
[2S,3S,4S,5S,5(2R,3S)]-3-Azido-5-(3-O-benzyl-1,2,3-trihy-
droxy-1,2-O-isopropylidene)-2-methoxy-4-methyltetrahydro-
furan (10e)
According to the General Procedure the reaction of furanoside 8e
(0.35 g, 0.1 mmol) with Tf2O (58.0 mg, 0.2 mmol) in pyridine fol-
lowed by the treatment of triflate 9e with NaN3 (33.0 mg, 0.8 mmol)
gave 26.0 mg (0.07 mmol, 69%) of 10e as a colorless oil; Rf = 0.68
(Et2O–n-pentane, 1:1); [a]D20 +41.0 (c 1.00, CHCl3).
3
1H NMR (300 MHz, CDCl3): d = 1.13 [d, J (4,4-CH3) = 7.3 Hz,
3 H, 4-CH3], 1.32, 1.36, 1.45, 1.56 [s each, 12 H, C(CH3)2], 2.70 (m,
3
1 H, 4-H), 3.40 (s, 3 H, OCH3), 3.82 (dd, J5,6 = 9.6 Hz,
3J6,7 = 1.9 Hz 1 H, 6-H), 3.96 (dd, 3J2,3 = 2.4 Hz, 3J3,4 = 6.0 Hz, 1 H,
3
3
3-H), 4.25 (dd, J4,5 = 6.2 Hz, 1 H, 5-H), 4.29 (dd, J8,9 = 2.4 Hz,
3J9,10 = 5.2 Hz 1 H, 9-H), 4.38 (dd, J7,8 = 8.1 Hz 1 H, 7-H), 4.60
3
(dd, 3J7,8 = 8.1 Hz, 1 H, 8-H), 4.84 (d, 3J2,3 = 2.4 Hz, 1 H, 2-H), 5.50
(d, 3J9,10 = 5.2 Hz, 1 H, 10-H).
IR (ATR): 2987, 2932, 2879, 2099, 1455, 1370, 1251, 1214, 1169,
1104, 1065, 1026, 967, 856 cm–1.
13C NMR (75 MHz, CDCl3): d = 13.8 (4-CH3), 24.4, 24.9, 25.6,
26.0 [C(CH3)2], 37.8 (C-4), 55.5 (OCH3), 66.3 (C-9), 69.7 (C-8),
70.6 (C-7), 70.8 (C-3), 76.9 (C-6), 83.3 (C-5), 96.5 (C-10), 106.6
(C-2), 108.6, 109.0 [C(CH3)2].
HRMS-ESI (EM): m/z calcd for [C17H27N3O7 + Na]+: 408.1741;
found: 408.1744.
3
1H NMR (300 MHz, CDCl3): d = 1.23 [d, J (4,4-CH3) = 7.0 Hz,
3 H, 4-CH3], 1.41, 1.43 [s each, 6 H, C(CH3)2], 2.16 (m, 1 H, 4-H),
3.30 (s, 3 H, OCH3), 3.50 (dd, 3J2,3 = 1.9 Hz, 3J3,4 = 5.0 Hz, 1-H, 3-
3
2
H), 3.59 (dd, J7,8A = 6.3 Hz, J8A,8B = 10.4 Hz, 1 H, 8-HA), 3.68 –
3
3
3.74 (m, 2 H, 5-H, 8-HB), 3.83 (dd, J5,6 = 7.0 Hz, J6,7 = 7.6 Hz,
3
1 H, 6-H), 4.15 (ddd, J7,8B = 3.3 Hz, 1 H, 7-H), 4.62 (d,
[2S,3S,4S,5S,5(2S,3S,4R,5S)]-3-Azido-5-(2,3,4-trihydroxy-5-hy-
droxymethyl-2,3;4,5¢-di-O-isopropylidene-2-tetrahydrofuran-
yl)-2-methoxy-4-methyltetrahydrofuran (10c)
According to the General Procedure, the reaction of furanoside 8c
(0.26 g, 0.7 mmol) with Tf2O (0.36 g, 1.3 mmol) in pyridine fol-
lowed by the treatment of triflate 9c with NaN3 (0.12 g, 1.9 mmol)
gave 0.17 g (0.44 mmol, 61%) of 10c as a colorless solid; mp
91.4 °C; Rf = 0.52 (EtOAc–cyclohexane, 1:1); [a]D20 –39.6 (c 1.07,
CHCl3).
2J9A,9B = 2.3 Hz,, 2 H, 9-CH2), 4.79 (d, J2,3 = 1.9 Hz, 1 H, 2-H),
3
7.27–7.36 (m, 5 H, C6H5).
13C NMR (75 MHz, CDCl3): d = 17.2 (4-CH3), 27.0, 27.2
[C(CH3)2], 42.9 (C-4), 55.1 (OCH3), 70.7 (C-6), 72.8 (C-8), 73.4
(C-9), 79.1 (C-3) 79.3 (C-7), 84.9 (C-5), 107.7, 110.0 [C(CH3)2],
127.6, 127.7, 128.3 (CHAr), 138.1 (CAr).
HRMS-ESI (EM): m/z calcd for [C19H27N3O5 + Na]+: 400.1843;
found 400.1452.
IR (ATR): 2970, 2934, 2902, 2825, 2103, 1454, 1379, 1275, 1245,
1081, 1177, 1127, 1021, 970, 833 cm–1.
Aminofuranosides 11a–d; General Procedure
Azide 10 (1.0 equiv), Pd/C (10 mol%), and Boc2O (1.2 equiv) were
suspended in THF (1 mL/mmol). The mixture was stirred at r.t. for
9 h under H2 atmosphere. The reaction was stopped by filtration
through a pad of kieselguhr with Et2O (10 mL/mmol) and the filtrate
was concentrated. The residue was purified by flash column chro-
matography on silica gel (Et2O–n-pentane, 1:3 → 2:1).
3
1H NMR (300 MHz, CDCl3): d = 1.29 [d, J (4,4-CH3) = 6.9 Hz,
3 H, 4-CH3], 1.37, 1.43, 1.44, 1.49 [s each, 12 H, C(CH3)2], 2.59 (m,
3
1 H, 4-H), 3.38 (s, 3 H, OCH3), 3.56 (dd, J2,3 = 2.3 Hz,
3J3,4 = 5.8 Hz, 1 H, 3-H), 3.99–4.13 (m, 4 H, 5-H, 9-H, 10-HA, 10-
3
HB), 4.25 (d, J7,8 = 2.1 Hz 1 H, 8-H), 4.55 (s, 1 H, 7-H), 4.84 (d,
3J2,3 = 2.3 Hz, 1 H, 2-H).
Synthesis 2010, No. 5, 749–756 © Thieme Stuttgart · New York

PAPER
Stereoselective Synthesis of 2-Amino-3-C-methyl-2,3-dideoxyaldoses
755
[2S,3S,4S,5S,5(1R)]-3-[N-(tert-Butoxycarbonyl)amino]-5-(1,2-
dihydroxy-1,2-O-isopropylideneethyl)-2-methoxy-4-methyltet-
rahydrofuran (11a)
9 H, C(CH3)3], 2.34 (m, 1 H, 4-H), 3.35 (s, 3 H, OCH3), 3.73 (br d,
3J3,4 = 6.6 Hz, 1 H, 3-H), 3.99–4.12 (m, 4 H, 5-H, 9-H, 10-HA, 10-
HB), 4.27 (d, 3J7,8 = 2.3 Hz, 1 H, 8-H), 4.54 (br s, 1 H, 7-H), 4.82 (s,
1 H, NH), 5.48 (d, 3J2,3 = 1.5 Hz, 1 H, 2-H).
According to the General Procedure, 10a (0.18 g, 0.7 mmol) was
converted with Pd/C (35.0 mg, 10 mol%) and Boc2O (0.18 g,
0.8 mmol) under H2 atmosphere to 11a (0.16 g, 0.48 mmol, 70%);
13C NMR (100 MHz, CDCl3): d = 18.9 (4-CH3), 19.7, 26.6, 28.4,
28.5 [C(CH3)2], 28.4 [C(CH3)3], 40.0 (C-4), 54.7 (OCH3), 60.1 (C-
10), 62.2 (C-8), 72.3 (C-3), 73.6 (C-9), 78.9 [C(CH3)3], 85.2 (C-5),
86.8 (C-7), 109.8 (C-2), 97.5, 111.7 [C(CH3)2], 115.3 (C-6), 155.4
(C=O).
20
colorless oil; Rf = 0.38 (Et2O–n-pentane, 1:1); [a]D +8.7 (c 0.71,
CHCl3).
IR (ATR): 3353, 2983, 2913, 2831, 1695, 1518, 1457, 1366, 1244,
1221, 1173, 1105, 1063, 1022 cm–1.
Anal. Calcd for C22H37NO9: C, 57.50; H, 8.12; N, 3.05. Found: C,
57.40; H, 8.15; N, 3.15.
3
1H NMR (300 MHz, CDCl3): d = 1.28 [d, J (4,4-CH3) = 7.4 Hz,
3 H, 4-CH3], 1.38, 1.48 [s each, 6 H, C(CH3)2], 1.42 [s, 9 H,
C(CH3)3], 1.96 (m, 1 H, 4-H), 3.33 (s, 3 H, OCH3), 4.31–4.39 (m,
1 H, 5-H), 3.61–3.69 (m, 1 H, 6-H), 3.73–3.82 (m, 2 H, 7-HA, 7-
HB), 4.10 (dd, 3J2,3 = 1.2 Hz, 3J3,4 = 8.5 Hz, 1 H, 3-H), 4.78 (s, 1 H,
NH), 5.31 (br d, 3J2,3 = 1.2 Hz, 1 H, 2-H).
13C NMR (75 MHz, CDCl3): d = 19.6 (4-CH3), 24.6, 26.0
[C(CH3)2], 28.3 [C(CH3)3], 40.2 (C-4), 54.6 (OCH3), 62.2 (C-7),
66.1 (C-3), 76.4 (C-6), 79.2 [C(CH3)3], 85.6 (C-5), 109.3 (C-2),
109.8 [C(CH3)2], 155.0 (C=O).
[2S,3S,4S,5S,5(2R,3R,4R,5R)]-3-[N-(tert-Butoxycarbonyl)ami-
no]-5-(2,3,4-trihydroxy-3,4-O-isopropylidene-5-O-methyl-2-
tetrahydrofuranyl)-2-methoxy-4-methyltetrahydrofuran (11d)
According to the General Procedure, 10d (0.11 g, 0.3 mmol) was
converted with Pd/C (16.5 mg, 10 mol%) and Boc2O (0.08 g,
0.4 mmol) under H2 atmosphere to 11d (84.6 mg, 0.21 mmol,
20
65%); light yellow oil; Rf = 0.44 (Et2O–n-pentane, 1:1); [a]D
–25.3 (c 0.75, CHCl3).
IR (ATR): 3360, 2978, 2932, 2835, 2830, 1704, 1518, 1457, 1368,
1242, 1211, 1163, 1103, 1072, 1023 cm–1.
Anal. Calcd for C16H29NO6: C, 57.99; H, 8.82; N, 4.23. Found: C,
57.96; H, 8.88; N, 4.28.
3
1H NMR (500 MHz, CDCl3): d = 1.26 [d, J (4,4-CH3) = 7.2 Hz,
[2S,3S,4S,5S,5(2R,3S,4S,5R,6R)]-3-[N-(tert-Butoxycarbon-
yl)amino]-5-(3,4,5,6-tetrahydroxy-3,4;5,6-di-O-isopropylidene-
2-tetrahydropyranyl)-2-methoxy-4-methyltetrahydrofuran
(11b)
According to the General Procedure, 10b (67.0 mg, 0.2 mmol) was
converted with Pd/C (10.0 mg, 10 mol%) and Boc2O (53.0 mg,
0.2 mmol) under H2 atmosphere to 11b (55.1 mg, 0.12 mmol,
70%); colorless solid; mp 145.4 °C; Rf = 0.24 (Et2O–n-pentane,
1:1); [a]D20 –84.3 (c 0.73, CHCl3).
3 H, 4-CH3], 1.33, 1.50 [s each, 6 H, C(CH3)2], 1.43 [br s, 9 H,
C(CH3)3], 1.91 (m, 1 H, 4-H), 3.34, 3.38 (s each, 3 H each, OCH3),
3
3.64–3.77 (m, 2 H, 3-H, 5-H), 4.06 (dd, J5,6 = 8.5 Hz,
3
3J6,7 = 1.8 Hz, 1 H, 6-H), 4.57 (d, J7,8 = 6.1 Hz, 1 H, 8-H), 4.78–
4.81 (m, 2 H, 2-H, 7-H), 4.88 (s, 1 H, NH), 4.97 (s, 1 H, 9-H).
13C NMR (100 MHz, CDCl3): d = 18.5 (4-CH3), 25.3, 26.7
[C(CH3)2], 28.4 [C(CH3)3], 43.9 (C-4), 54.8, 55.9 (OCH3), 63.8 (C-
3), 79.6 [C(CH3)3], 81.7 (C-6), 84.3 (C-8), 85.1 (C-5), 89.5 (C-7),
108.8 (C-2), 109.9 [C(CH3)2], 112.7 (C-9), 155.1 (C=O).
IR (ATR): 3350, 2979, 2935, 2897, 1701, 1522, 1457, 1368, 1253,
1211, 1167, 1101, 1065, 1001 cm–1.
HRMS-ESI (EM): m/z calcd for [C19H33NO8 + Na]+: 426.2098;
found: 426.2099.
3
1H NMR (400 MHz, CDCl3): d = 1.20 [d, J (4,4-CH3) = 6.9 Hz,
3 H, 4-CH3], 1.32, 1.35, 1.44, 1.53 [s each, 12 H, C(CH3)2], 1.43 [s,
9 H, C(CH3)3], 2.24 (m, 1 H, 4-H), 3.34 (s, 3 H, OCH3), 3.80 (br d,
3J5,6 = 9.5 Hz, 1 H, 6-H), 4.27–4.31 (m, 2 H, 3-H, 5-H), 4.32 (dd,
Acknowledgment
This work was supported by the Deutsche Forschungsgemeinschaft
(SFB 424) and the Fonds der Chemischen Industrie.
3
3J8,9 = 2.3 Hz, 3J9,10 = 5.1 Hz, 1 H, 9-H), 4.42 (dd, J7,6 = 1.9 Hz,
3J7,8 = 8.0 Hz, 1 H, 7-H), 4.59 (dd, 3J8,9 = 2.3 Hz, 1 H, 8-H), 4.79 (s,
1 H, NH), 5.49 (d, 3J2,3 = 2.6 Hz, 1 H, 2-H), 5.51 (d, 3J9,10 = 5.1 Hz,
1 H, 10-H).
13C NMR (100 MHz, CDCl3): d = 13.4 (4-CH3), 24.8, 24.9, 25.8,
26.0 [C(CH3)29, 28.3 [C(CH3)3], 36.6 (C-4), 55.5 (OCH3), 66.4 (C-
3), 70.5 (C-9), 70.8 (C-8), 70.9 (C-7), 76.6 (C-6), 77.3 [C(CH3)3],
78.5 (C-5), 96.4 (C-10), 109.3 (C-2), 108.7, 109.1 [C(CH3)2], 155.1
(C=O).
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[2S,3S,4S,5S,5(2S,3S,4R,5S)]-3-[N-(tert-Butoxycarbonyl)ami-
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According to the General Procedure, 10c (0.17 g, 0.4 mmol) was
converted with Pd/C (22.0 mg, 10 mol%) and Boc2O (0.11 g,
0.5 mmol) under H2 atmosphere to 11c (0.12 g, 0.26 mmol, 62%);
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3
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Synthesis 2010, No. 5, 749–756 © Thieme Stuttgart · New York

756
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Synthesis 2010, No. 5, 749–756 © Thieme Stuttgart · New York