Total synthesis of dapiramicin B

Article abstract of DOI:10.1016/j.tetlet.2006.06.001

The first total synthesis of dapiramicin B, a nucleoside antibiotic, is described. The characteristic N-glycoside linkage in dapiramicin B was effectively constructed by way of the Pd-catalyzed coupling reaction of a heptopyranosylamine with a bromopyrrol

Full text of DOI:10.1016/j.tetlet.2006.06.001

Tetrahedron Letters 47 (2006) 5747–5750
Total synthesis of dapiramicin B
Hiroyuki Ohno, Takashi Terui, Takafumi Kitawaki and Noritaka Chida*
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi, Kohoku-ku,
Yokohama 223-8522, Japan
Received 18 May 2006; revised 29 May 2006; accepted 1 June 2006
Available online 19 June 2006
Abstract—The first total synthesis of dapiramicin B, a nucleoside antibiotic, is described. The characteristic N-glycoside linkage in
dapiramicin B was effectively constructed by way of the Pd-catalyzed coupling reaction of a heptopyranosylamine with a bromo-
pyrrolopyrimidine derivative.
Ó 2006 Elsevier Ltd. All rights reserved.
6'
Me
OH
O
OMe
4
Dapiramicin B (1) is a nucleoside antibiotic produced by
Micromonospora sp. SF-1917, and reported to show
weak in vivo activity against the sheath blight of rice
plants caused by Rhizoctonia solani in a green house
test.1 The structurally related antibiotic, dapiramicin A
which is more potent than dapiramicin B, has been also
isolated from the same microorganism. The structure of
dapiramicin A was determined by careful spectral and
degradation studies to be 2-[40-(400-O-methyl-b-D-gluco-
pyranosyl)-60-deoxy-a-D-glucopyranosyl]amino-5-cya-
no-4-methoxy-7H-pyrrolo[2,3-d]pyrimidine (Fig. 1).2 By
spectral comparison, it was shown that the structure of
dapiramicin B (1) was closely related to dapiramicin
A, and assigned to be a 60-hydroxylated derivative of
dapiramicin A possessing a b-N-glycoside linkage.2
The structures of dapiramicins are unusual and quite
unique among nucleoside antibiotics with respect to
the N-glycoside structures; while conventional nucleo-
side antibiotics bear a sugar at the endocyclic nitrogen
in the heterocycles, dapiramicins are glycosylated at
the exocyclic nitrogen. In spite of their structural fea-
ture, no synthetic approach to dapiramicins has been
reported. In this letter, we report the first total synthesis
of dapiramicin B (1), which fully confirmed its unique
structure.
CN
4"
5
MeO
O 1'
O
N
HO
HO1"
HO
7
1
N
HO
N
2
N
H
H
dapiramicin A
OMe
4
CN
5
OH
O
N
4"
6' OH
O
O
7
1
MeO
HO
N
2
N
H
N
HO1"
HO
H
HO 1'
dapiramicin B (1)
Pd-catalyzed
N-arylation
OMe
4
CN
5
OMPM
O1'
6
N
4'
OMPM
O 1
7
1
N
MeO
MPMO
N
O
+
2
Br
NH2
SEM
MPMO
MPMO
MPMO
3
2
O
CN
4
5
HN
7
1
D
-cellobiose
N
2
H2N
N
H
4
Figure 1. Structures of dapiramicins and retrosynthetic route to
dapiramicin (1). MPM = –CH2C6H4(p-OMe), SEM = –CH2O-
CH2CH2SiMe3.
Our retrosynthetic analysis (Fig. 1) suggested that the
N-glycoside structure in 1 would be constructed by the
Pd-catalyzed coupling reaction of protected glycosyl-
B
amine 2 with bromo-heterocycle derivative 3. This meth-
odology, an important extension of the Buchwald–
Hartwig N-arylation reaction,3 proved to be effective
for the construction of the N-glycoside bond between a
Keywords: Dapiramicin B; Nucleoside antibiotic; Total synthesis;
Pd-Catalyzed; N-Arylation.
*
Corresponding author. Tel./fax: +81455661573; e-mail: chida@
applc.keio.ac.jp
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.06.001

5748
H. Ohno et al. / Tetrahedron Letters 47 (2006) 5747–5750
OAc
OAc
CH2N2 in Et2O
silicic acid
NaHCO3
O
4
1) Ac2O
pyridine
CN
SEMCl
NaH
O
AcO
AcO
O
D
-cellobiose
O
HN
2
N3
2) TMSN3
SnCl4
CH2Cl2
AcO
4
7
AcO
DMF
36%
OAc
MeOH
sonication
N
H2N
N
SEM
5
10
94% overall
OMe
4
O
4
CN
6
1) NaOMe
OR
O
SbBr3
-BuONO
CN
MP
O
5
O
MeOH
3
O
t
3
O
N
2
MeN
RO
3
N3
+
RO
2) (p-MeO)C6H4CH(OMe)2
Amberlyst 15 (H+ form)
DMF, 50 °C, 40 hPa
7
1
N
OR
CH2Br2
OR
N
H2N
N
0 °C
H2N
N
SEM
SEM
NaH, MPMCl
6 R = H
72%
Bu4NI, imidazole
15-crown-5 ether
DMSO, 70 °C
54%
12 (41%)
11 (43%)
63% overall
7 R = MPM
Scheme 2.
OMPM
NaBH3CN
OMPM
O
For O-methylation at the C-4 position, compound 10
was treated with Me3OBF4 or Mitsunobu reagents
(Ph3P, diethyl azodicarboxylate and MeOH), however,
the desired product 12 could not be obtained in accept-
able yields. After several attempts, it was found that the
reaction of 10 with ethereal diazomethane in the pres-
ence of silicic acid11 and NaHCO3 in MeOH under son-
ication gave improved results, and methyl ether 12 and
its N-methyl isomer 11 were obtained in 41% and 43%
isolated yields, respectively. Substitution of the amino
function in 12 into a bromo substituent was successfully
achieved by treatment of 12 with SbBr3 and t-BuONO in
NaH, MeI
O
TFA, MS4A
HO
O
MPMO
N3
DMF, 50 °C
DMF, 50 °C
MPMO
MPMO
92%
84%
OMPM
8
OMPM
H2
OMPM
O 1
4'
O
10% Pd on carbon
MeO
MPMO
1'
2
O
N3
MPMO
EtOH / EtOAc (1/1)
2 OMPM
MPMO
9
Scheme 1. MP = (p-MeO)C6H4–.
12
sugar and an exocyclic nitrogen of heterocycles4 and was
successfully utilized in our total synthesis of spicamycin,
a nucleoside antibiotic possessing the similar N-glycoside
bond between a sugar moiety and C-6 amino group of
adenine.5 The disaccharide–amine 2 was planned to be
prepared from D-cellobiose, while the bromo-heterocycle
3 was envisioned as arising from the known 2-amino-5-
cyanopyrrolo[2,3-d]pyrimidin-4-one (4).6
CH2Br2 to afford 310 in 72% yield.
Having completed the preparation of both glycosyl-
amine 2 and heterocycle 3, we next investigated the
key reaction, construction of the N-glycoside (Scheme
3). Reaction of 2 with 3 (200 mol % to 2) under the
similar reaction conditions employed in the synthesis
of spicamycin [Pd2(dba)3 (10 mol % to 2), (S)-BINAP
(20 mol % to 2) and NaO-t-Bu (150 mol % to 2) in tolu-
ene]3f,4,5b at 100 °C for 1 h in a sealed tube successfully
provided coupling products 13b10 and 13a10 in moderate
yields (13b in 30% and 13a in 12% yields from 9, respec-
tively). After some attempts, 13b and 13a were obtained
in 55% and 14% isolated yields, respectively, when the
reaction was carried out in the presence of the increased
amount of 3 (250 mol % to 2), Pd2(dba)3 (20 mol % to 2)
and (S)-BINAP (60 mol % to 2) in toluene at 80 °C
for 6 h.13 The observed signals of anomeric protons
Synthesis of glycosylamine 2 commenced from commer-
cially available D-cellobiose (Scheme 1). O-Acetylation
of D-cellobiose, followed by introduction of an azide
function to the anomeric carbon provided the known
b-azide derivative 5.7 Removal of the O-acetyl groups
and subsequent treatment with anisaldehyde dimethyl
acetal gave 40,60-O-anisylidene compound 68 in 63%
yield. The remaining hydroxy groups in 6 was fully pro-
tected as O-MPM ethers to give 7 (54% yield). The anisi-
lydene acetal in 7 was regioselectively cleaved by the
action of NaBH3CN in the presence of trifluoroacetic
acid (TFA)9 to afford 8 in 84% yield, whose hydroxy
group was converted into methyl ether to provide 9 in
92% yield. Hydrogenation of 9 in the presence of 10%
Pd on carbon cleanly afford glycosylamine 2,10 whose
anomeric configuration at C-1 was confirmed to be b
by 1H NMR analysis (H-1; d = 4.06, J1,2 = 8.4 Hz).
Since amine 2 was found to be not so stable and was
thus used without purification in the next coupling
reaction.
0
0
of the N-glycoside moiety in 13b (d = 5.31, J1 ;2
¼
0
0
0
9:0, J1 ;NH ¼ 9:0 Hz) and 13a (d = 5.77, J1 ;2 ¼ 4:8,
J1 ;NH ¼ 6:0 Hz) in the 1H NMR spectra clearly assigned
0
their anomeric configurations. The correlation between
H-10 (anomeric proton) and C-2 on the heterocycle ob-
served in HMBC experiments of 13b also supported its
N-glycoside structure. Whereas an anomerically pure
b-glycosylamine 2 was employed as the starting mate-
rial, the coupling products 13a and 13b were obtained
as an anomeric mixture. These results suggested that
the anomerization of 2, 13a and/or 13b had occurred
during the reaction.14 Similar thermal anomerization
of glycoslyamines15a and N-glycosides possessing a pro-
tected adenine5b and other substituents,15 which are pro-
posed to involve imine or iminium intermediates,15c
have been reported from several groups.
The requisite counter part of the coupling reaction, bro-
mo-heterocycle 3 was synthesized as shown in Scheme 2.
Treatment of the known 5-cyanopyrrolopyrimidine 4,6
prepared in 70% yield by condensation of 2-chloro-2-
formylacetonitrile with 2,4-diamino-6-hydroxypyrimi-
dine, with 2-(trimethylsilyl)ethoxymethyl chloride
(SEMCl) in the presence of NaH gave 10 in 36% yield.
16
Finally, treatment of 13b with excess BF3OEt2 in
CH2Cl2 at 0 °C for 30 min removed the O-MPM as well

H. Ohno et al. / Tetrahedron Letters 47 (2006) 5747–5750
5749
OMe
Pd2(dba)3 (20 mol % to 2)
(S)-BINAP (60 mol % to 2)
NaOt-Bu (150 mol % to 2)
CN
OMe
N
4
5
OMPM
O 1'
CN
OMPM
O 1"
6'
N
OMPM
O
4"
4'
7
+
2
3
N
MeO
MPMO
+
O
toluene
80 °C, 6 h
N
2
2'
N
N
(250 mol % to 2)
MPMO
2'
SEM
N
MPMO1'
H
MPMO
MPMO
N
SEM
H
13b (55% from 9)
13a (14% from 9)
BF3•OEt2
dapiramicin B (1)
CH2Cl2, 0
92%
°C
Scheme 3.
2880; (c) Suzuki, T.; Chida, N. Chem. Lett. 2003, 32, 190–
191.
6. Gangjee, A.; Vidwans, A.; Elzein, E.; McGuire, J. J.;
Queener, S. F.; Kisliuk, R. L. J. Med. Chem. 2001, 44,
1993–2003.
as N-SEM protecting groups to furnish dapiramicin B
(1) in 92% yield after purification with the reversed-
phase and gel filtration chromatographies. The physical
properties as well as spectral data (1H NMR and IR) of
20
synthetic specimen {mp 241–244 °C; ½aꢀD ꢁ36.3 (c 0.12,
}
´
7. Peto, C.; Batta, G.; Gyo¨rgydeak, Z.; Sztaricskai, F.
50% aqueous AcOH)} showed good accordance with
Liebigs Ann. Chem. 1991, 505–507.
those reported for natural dapiramicin B {mp 241–
8. All new compounds described in this paper were charac-
terized by 300 MHz 1H NMR, 75 MHz 13C NMR, IR and
mass spectrometric and/or elemental analyses.
20
243 °C; ½aꢀD ꢁ37.6 (c 1.0, 50% aqueous AcOH)}.2a
In summary, the first total synthesis of dapiramicin B (1)
has been accomplished. This synthesis fully confirmed
the proposed structure of the natural product and re-
vealed that the Pd-catalyzed N-arylation methodology
is highly effective for construction of N-glycoside struc-
tures in which an exocyclic nitrogen of the heterocycle is
connected to the sugar. Further study for the stereo-
selective synthesis of dapiramicin A based on the same
methodology is underway.
9. Furstner, A.; Radkowski, K.; Grabowski, J.; Wirtz, C.;
¨
Mynott, R. J. Org. Chem. 2000, 65, 8758–8762.
23
10. Data of compound 2: ½aꢀD +24.8 (c 1.00, CHCl3);
mmax (neat) 3400 and 3330 cmꢁ1 1H NMR (CDCl3,
;
300 MHz): d 7.31–7.18 (m, 12H), 6.88–6.72 (m, 12H),
5.01 (d, 1H, J = 10.8 Hz), 4.79 and 4.77 (2d, each 1H,
J = 10.5 Hz), 4.73 (d, 1H, J = 10.8 Hz), 4.69 (d, 2H,
J = 10.5 Hz), 4.65 and 4.63 (2d, each 1H, J = 10.8 Hz),
4.55 (d, 1H, J = 12.0 Hz), 4.43 (s, 2H), 4.32 (d, 1H,
J = 12.0 Hz), 4.31 (d, 1H, J = 8.5 Hz), 4.06 (d, 1H,
J = 8.4 Hz), 3.95 (dd, 1H, J = 9.0 and 9.0 Hz), 3.80–3.77
(m, 1H), 3.80 (s, 6H), 3.78, 3.78, 3.77 and 3.73 (4s, each
3H), 3.71 (dd, 1H, J = 11.4 and 0.9 Hz), 3.59 (dd, 1H,
J = 10.8 and 1.5 Hz), 3.57 (dd, 1H, J = 9.0 and 9.0 Hz),
3.54 (dd, 1H, J = 11.4 and 5.1 Hz), 3.48 (s, 3H), 3.34 (ddd,
1H, J = 9.0, 3.0 and 1.5 Hz), 3.30–3.16 (m, 4H) and 3.12
(dd, 1H, J = 9.0 and 8.4 Hz); 13C NMR (CDCl3,
300 MHz): d 159.09, 159.06, 159.00, 158.84, 158.74,
131.47, 130.88, 130.70, 130.65, 130.62, 129.80, 129.78,
129.75, 129.63, 129.40, 129.33, 128.92, 113.74, 113.67,
113.60, 113.56, 113.33, 102.27, 86.18, 84.51, 83.58, 82.30,
82.21, 79.88, 76.58, 75.80, 75.13, 75.04, 74.66, 74.52, 74.40,
72.94, 72.85, 68.74, 67.81, 60.51, 55.21, 55.19, 55.17, 55.11
and 55.06; MS (FAB) m/z 1076 (M+H)+. Data of
References and notes
1. Shomura, T.; Nishizawa, N.; Iwata, M.; Yoshida, J.; Ito,
M.; Amano, S.; Koyama, M.; Kojima, M.; Inouye, S.
J. Antibiot. 1983, 36, 1300–1304.
2. (a) Nishizawa, N.; Kondo, Y.; Koyama, M.; Omoto, S.;
Iwata, M.; Tsuruoka, T.; Inouye, S. J. Antibiot. 1984, 37,
1–5; (b) Seto, H.; Otake, N.; Koyama, M.; Ogino, H.;
Kodama, Y.; Nishizawa, N.; Tsuruoka, T.; Inouye, S.
Tetrahedron Lett. 1983, 24, 495–498.
3. (a) Muci, A. R.; Buchwald, S. L. In Topics in Current
Chemistry; Miyaura, N., Ed.; Springer: Berlin, 2001; Vol.
219, pp 131–209; Hartwig, J. F. In Modern Arene
Chemistry; Astruc, C., Ed.; Wiley-VCH: Weinheim,
2002; pp 107–168; Wolfe, J. P.; Wagaw, S.; Marcoux,
J.-F.; Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805–
818; (b) Wolfe, J. P.; Tomori, H.; Sadighi, J. P.; Yin, J.;
Buchwald, S. L. J. Org. Chem. 2000, 65, 1158–1174; (c)
Strieter, E. R.; Blackmond, D. G.; Buchwald, S. L. J.
Am. Chem. Soc. 2003, 125, 13978–13980; (d) Huang, X.;
Anderson, K. W.; Zim, D.; Jiang, L.; Klapars, A.;
Buchwald, S. L. J. Am. Chem. Soc. 2003, 125, 6653–6655;
(e) Wolfe, J. P.; Buchwald, S. L. J. Org. Chem. 2000, 65,
1144–1157; (f) Wolfe, J. P.; Wagaw, S.; Buchwald, S. L.
J. Am. Chem. Soc. 1996, 118, 7215–7216.
compound 3: mp 113–116 °C; mmax (neat) 2235 cmꢁ1 1H
;
NMR (CDCl3, 300 MHz): d 7.67 (s, 1H), 5.57 (s, 2H), 4.17
(s, 3H), 3.54 (t, 2H, J = 8.1 Hz), 0.91 (t, 2H, J = 8.1 Hz)
and ꢁ0.05 (s, 9H); 13C NMR (CDCl3, 75 MHz): d 162.92,
152.29, 145.35, 133.44, 113.68, 103.58, 85.98, 73.74, 67.44,
55.25, 17.60 and ꢁ1.53; MS (EI) m/z 384 (M+2, 13%), 382
(M+, 13), 341 (29), 339 (30), 326 (73), 324 (72), 311 (23),
309 (27), 268 (62), 266 (62), 245 (23), 103 (26), 73 (100);
HRMS (EI) m/z 384.0441, calcd for C14H1981BrN4O2Si
23
(M+); 384.0440. Data of compound 13a: ½aꢀD +56.6 (c 0.80,
1
CHCl3); mmax (neat) 3440, 3370 and 2210 cmꢁ1; H NMR
(CDCl3, 300 MHz): d 7.42 (s, 1H), 7.33–7.08 (m, 12H),
6.86–6.66 (m, 12H), 5.80 (d, 1H, exchangeable with D2O,
J = 6.0 Hz), 5.77 (dd, 1H, J = 6.0 and 4.8 Hz), 5.48 and
5.38 (2d, each 1H, J = 10.7 Hz), 4.98 (d, 1H, J = 11.4 Hz),
4.72 (d, 1H, J = 10.5 Hz), 4.70 (d, 1H, J = 10.8 Hz), 4.66
(d, 1H, J = 10.5 Hz), 4.65 (d, 1H, J = 11.4 Hz), 4.60 (d,
1H, J = 11.3 Hz), 4.59 (d, 1H, J = 10.8 Hz), 4.54 (d, 1H,
J = 11.7 Hz), 4.43 (s, 2H), 4.43 (d, 1H, J = 11.3 Hz), 4.29
(d, 1H, J = 6.9 Hz), 4.29 (d, 1H, J = 11.7 Hz), 4.05 (s,
4. Chida, N.; Suzuki, T.; Tanaka, S.; Yamada, I. Tetrahedron
Lett. 1999, 40, 2573–2576.
5. (a) Suzuki, T.; Tanaka, S.; Yamada, I.; Koashi, Y.;
Yamada, K.; Chida, N. Org. Lett. 2000, 2, 1137–1140; (b)
Suzuki, T.; Suzuki, S. T.; Yamada, I.; Koashi, Y.;
Yamada, K.; Chida, N. J. Org. Chem. 2002, 67, 2874–

5750
H. Ohno et al. / Tetrahedron Letters 47 (2006) 5747–5750
3400 and 2235 cmꢁ1 1H NMR (DMSO-d6/D2O = 10/1,
;
3H), 4.02 (dd, 1H, J = 9.4 and 7.8 Hz), 3.85 (dd, 1H,
J = 10.8 and 2.4 Hz), 3.79–3.67 (m, 4H), 3.79 and 3.78 (2s,
each 3H), 3.75 (s, 6H), 3.74 and 3.72 (2s, each 3H), 3.60–
3.45 (m, 2H), 3.54 (t, 2H, J = 8.3 Hz), 3.48 (s, 3H), 3.33–
3.14 (m, 4H), 0.88 (t, 2H, J = 8.3 Hz) and ꢁ0.06 (s, 9H);
13C NMR (CDCl3, 75 MHz): d 163.59, 159.23, 159.18,
159.08, 158.97, 158.90, 158.85, 153.81, 131.41, 130.90,
130.71, 130.68, 130.61, 129.87, 129.84, 129.70, 129.57,
129.50, 129.43, 129.32, 128.98, 115.17, 113.71, 113.68,
113.58, 113.55, 113.52, 113.40, 102.66, 98.24, 85.47, 84.51,
82.24, 79.75, 79.68, 77.77, 77.20, 76.26, 75.17, 74.96, 74.52,
74.43, 73.33, 72.91, 72.80, 72.49, 70.47, 68.75, 67.54, 66.92,
60.53, 55.24, 55.20, 55.18, 55.15, 55.12, 55.07, 54.09, 17.74
and ꢁ1.41; MS (FAB) m/z 1379 (M+H)+. Anal. Calcd for
C75H91N5O18Si: C, 65.34; H, 6.65; N, 5.08. Found: C,
300 MHz): d 7.81 (s, 1H), 5.04 (d, 1H, J = 8.3 Hz), 4.27
(d, 1H, J = 7.8 Hz), 3.97 (s, 3H), 3.70–3.55 (m, 1H), 3.50–
3.20 (m, 9H), 3.40 (s, 3H), 3.01 (dd, 1H, J = 8.4 and
7.8 Hz), and 2.92 (dd, 1H, J = 9.3 and 8.4 Hz); 13C NMR
(DMSO-d6, 75 MHz, 50 °C): d 162.4, 158.8, 154.7, 131.3,
115.9, 102.7, 96.53, 82.43, 82.05, 80.16, 79.30, 76.06 (2C),
75.80, 75.38, 73.43, 71.90, 60.52, 60.40, 59.36, 53.08;
HRMS (FAB) m/z 528.1938, calcd for C21H29N5O11
1
(M+H)+ 528.1942. The IR and H NMR data were fully
identical with those reported for natural dapiramicin B
(13C NMR data of natural dapiramicin B have not been
reported).2a
11. Nishiyama, H.; Nagase, H.; Ohno, K. Tetrahedron Lett.
1979, 48, 4671–4674.
12. Francom, P.; Janeba, Z.; Shibuya, S.; Robins, M. J.
J. Org. Chem. 2002, 67, 6788–6796.
25
65.47; H, 6.64; N, 4.89. Data of compound 13b: ½aꢀD +11.9
(c 0.80, CHCl3); mmax (neat) 3350 and 2230 cmꢁ1 1H
;
NMR (CDCl3, 300 MHz, 45 °C): d 7.38 (s, 1H), 7.32–7.11
(m, 12H), 6.85–6.76 (m, 12H), 5.44 and 5.37 (2d, each 1H,
J = 10.5 Hz), 5.31 (dd, 1H, J = 9.0 and 9.0 Hz), 5.19 (d,
1H, exchangeable with D2O, J = 9.0 Hz), 5.05 (d, 1H, J =
10.8 Hz), 4.76 (d, 1H, J = 11.1 Hz), 4.74 (d, 1H, J = 11.0
Hz), 4.70 (d, 1H, J = 10.8 Hz), 4.69 (d, 1H, J = 10.8 Hz),
4.68 (d, 1H, J = 10.8 Hz), 4.65 (d, 1H, J = 11.0 Hz), 4.63
(d, 1H, J = 11.1 Hz), 4.52 (d, 1H, J = 11.9 Hz), 4.48 and
4.43 (2d, each 1H, J = 11.4 Hz), 4.37 (d, 1H, J = 7.2 Hz),
4.28 (d, 1H, J = 11.9 Hz), 4.04 (s, 3H), 4.04 (dd, 1H,
J = 9.0 and 9.0 Hz), 3.83 (dd, 1H, J = 11.3 and 3.3 Hz),
3.80–3.72 (m, 1H), 3.80 (s, 6H), 3.79, 3.77, 3.76 and 3.75
(4s, each 3H), 3.70 (dd, 1H, J = 9.0 and 9.0 Hz), 3.60(dd,
1H, J = 11.3 and 1.5 Hz), 3.58–3.47 (m, 2H), 3.53 (t, 2H,
J = 8.0 Hz), 3.48 (s, 3H), 3.44 (ddd, 1H, J = 9.0, 3.3 and
1.5 Hz), 3.35 (dd, 1H, J = 9.0 and 9.0 Hz), 3.31–3.22 (m,
3H), 0.88 (t, 2H, J = 8.0 Hz) and ꢁ0.05 (s, 9H); 13C NMR
(CDCl3, 75 MHz, 45 °C): d 163.63, 159.36, 159.24, 159.21,
159.05, 159.03, 158.90, 153.96, 131.52, 131.10, 130.91,
130.50, 130.33, 130.06, 129.87, 129.75, 129.60, 129.33,
129.26, 128.94, 115.01, 113.83, 113.77, 113.75, 113.68,
113.52, 102.34, 98.18, 85.69, 84.63, 84.05, 82.42, 80.20,
79.64, 76.58, 76.28, 75.30, 75.09, 74.75, 74.44, 74.20, 73.34,
73.02, 69.05, 67.80, 66.98, 60.45, 55.25, 55.20, 55.15, 55.07,
53.76, 17.82 and ꢁ1.41; MS (FAB) m/z 1379 (M+H)+.
13. When (R)-BINAP was employed as a ligand, the similar
reaction conditions (100 °C, 6 h) afforded 13b and 13a in
46% and 9% isolated yields from 9, respectively. Use of
other ligands such as 2-(dicyclohexylphosphino)biphe-
nyl,3b 2-(dicyclohexylphosphino)-20,40,60-triisopropylbi-
phenyl,3c or 2-(di-t-butylphosphino)binaphthyl,3d which
have been reported to be effective for the Pd-catalyzed
N-arylation of simple amines,3 significantly decreased the
yields of 13b and 13a.
14. When the toluene solutions of anomerically pure 13a and
13b (2 mM) were separately heated at 100 °C in sealed
tubes, both N-glycosides 13a and 13b showed thermal
anomerization and reached equilibrium at a:b = 1:1.8
after ca. 120 h.
15. (a) Rao, C. S.; Ratcliffe, A. J.; Fraser-Reid, B. J. Chem.
Soc., Perkin Trans. 1 1993, 1207–1211; Ogawa, T.;
Nakabayashi, S.; Shibata, S. Agric. Biol. Chem. 1983, 47,
281–285; (b) Owens, J. M.; Yeung, B. K. S.; Hill, D. C.;
Petillo, P. A. J. Org. Chem. 2001, 66, 1484–1486; Vaino,
A. R.; Szarek, W. A. J. Org. Chem. 2001, 66, 1097–1102;
Randell, K. D.; Johnston, B. D.; Green, D. F.; Pinto, B.
M. J. Org. Chem. 2000, 65, 220–226; Randell, K. D.;
Frandsen, T. P.; Stoffer, B.; Johnson, M. A.; Svensson, B.;
Pinto, B. M. Carbohydr. Res. 1999, 321, 143–156; (c)
Andrews, J. S.; Weimar, T.; Frandsen, T. P.; Svensson, B.;
Pinto, B. M. J. Am. Chem. Soc. 1995, 117, 10799–10804.
16. Molina, P.; Fresneda, P. M.; Delgado, S. J. Org. Chem.
2003, 68, 489–499.
24
Data of compound 1: mp 241–244 °C; ½aꢀD ꢁ36.3 (c
0.12, 50% aqueous AcOH), {lit.2a mp 241–243 °C;
20
½aꢀD ꢁ37.6 (c 1.00, 50% aqueous AcOH)}; mmax (KBr)