1,6-Anhydro-β-L-hexopyranoses as valuable building blocks toward the synthesis of L-gulosamine and L-altrose derivatives

Article abstract of DOI:10.1016/S0040-4039(00)02237-1

1,6-Anhydro-β-L-hexopyranoses as valuable building blocks toward the synthesis of L-gulosamine and L-altrose derivatives via the regioselective triflation and benzoylation of 1,6-anhydro β-L-idopyranose followed by S_N2 substitution with various

Full text of DOI:10.1016/S0040-4039(00)02237-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 1321–1324
1,6-Anhydro-b-
L
-hexopyranoses as valuable building blocks
toward the synthesis of
L
-gulosamine and -altrose derivatives
L
Shang-Cheng Hung,* Cheng-Chung Wang, Shu-Wen Chang and Chien-Sheng Chen
Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan
Received 4 October 2000; revised 13 November 2000; accepted 1 December 2000
Abstract—1,6-Anhydro-b-
derivatives via the regioselective triflation and benzoylation of 1,6-anhydro-b-
various nucleophiles as key steps is described here. © 2001 Elsevier Science Ltd. All rights reserved.
L
-hexopyranoses as valuable building blocks toward the synthesis of
L-gulosamine and L-altrose
L
-idopyranose followed by SN2 substitution with
As part of our progress in the synthesis of biologically
potent -gulosamine and
-hexoses,1 we have interest in
-altrose. Adenomycin, a nucleoside antibiotic with sig-
nificant anti-bacterial activity,2 contains
-gulosamine as
a key component (Scheme 1).
-Altrose3 is a potent
explored herein a convenient route to synthesize the
1,6-anhydro-b- -ido, -gulo, and -altropyranosyl sugars
and their applications in the preparation of
gulosamine and -altrose derivatives.
L
L
L
L
L-
L
L
L
constituent of extracellular polysaccharides from Bu-
A practical synthesis of 1,2:3,5-di-O-isopropylidene-b-
-idofuranose 1 from diacetone a- -glucose in three
tyrivibrio fibrisolvens strain CF3.4 Given the importance
L
D
of
of
L
-hexoses in the field of glycobiology and the study
steps in 57% overall yield was recently developed by
us.1a The results of compound 1’s hydrolysis in acidic
media at various temperatures followed by per-acetyla-
tion are shown in Table 1. In entries 2 and 3, treatment
of 1 with 0.2N H2SO4(aq) at 60 or 80°C often afforded
L
-gulosamine is unknown, there is a constant need to
develop efficient methodologies for their synthesis.
1,6-Anhydro-hexopyranoses are valuable synthons for
carbohydrate-based syntheses of oligosaccharides and
natural products.5 Their [3.2.1]bicyclic skeletons ensure
that not only a high degree of steric-approach control
occurs in their reactions, but also fewer protecting
groups at C1 and C6 are needed than their correspond-
ing pyranoses. After the cleavage of internal acetal,
further functional group transformation and glycosyla-
tion at C6 and C1, respectively, could be carried out.
a mixture of
5. When the hydrolyzed temperature was 35°C only
-idose was obtained (entry 1). Since it was unstable
and slowly rearranged to
-sorbose,6 per-acetylation
with acetic anhydride and pyridine gave -idopyranosyl
pentaacetate 27 and
-idofuranosyl pentaacetate 3 in 70
L
-idose and 1,6-anhydro-b-
L-idopyranose
L
L
L
L
and 26% yields, respectively. Hydrolysis of 1 in 0.2N
H2SO4(aq) or HCl(ethanol) at refluxing temperature
(entries 4 and 5) provided 5 (88%) as a single adduct,
which was per-acetylated to afford the triacetate 4 in
1,6-Anhydro-b-
L-hexopyranoses, which are known as
rare -form sugars, are laborious to prepare. We have
L
Scheme 1.
Keywords: carbohydrates; adenomycin; L-gulosamine; L-altrose.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)02237-1

1322
S.-C. Hung et al. / Tetrahedron Letters 42 (2001) 1321–1324
Table 1. The results of compound 1’s hydrolysis in acidic media followed by per-acetylation
Entry
Acidic media
t (°C)
Time (h)
Yield (%)
2
3
4
1
2
3
4
5
6
0.2N H2SO4 in H2O
0.2N H2SO4 in H2O
0.2N H2SO4 in H2O
0.2N H2SO4 in H2O
0.2N HCl in EtOH
Acidic resin in EtOH
35
60
80
Reflux
Reflux
Reflux
44
12
12
12
8
70
74
22
–
–
–
26
11
20
–
–
–
–
7
48
90
88
32
8
excellent yields. When the Amberlite-120 acidic resin
was used as the catalyst, the desired product was iso-
lated in low yield (entry 6).
89% yield, which is believed to be a potential precursor
in the synthesis of adenomycin.
Application of 5 toward the synthesis of L-altro sugars
With the key synthon 5 in hand, the distinction of three
free equatorial hydroxyls at C2, C3 and C4 was studied
is summarized in Scheme 3. Regioselective benzoylation
of 5 with 1.2 equiv. of benzoyl chloride in pyridine led
to the corresponding 2-OBz compound in 63% yield.
When 2.4 equiv. of BzCl was used, the dibenzoates 9
and 108 were isolated in 12 and 53% yields, respectively.
Triflation of 10 provided 11 (90%), the absolute
configuration of which was determined by X-ray single
crystal analysis.10 Nucleophilic substitution of 11 with
sodium nitrite furnished the C4-epimerized product 128
in 77% yield. Typical acetolysis only gave the 4-OAc
derivative and the 1,6-anhydro ring could be opened by
extra addition of 1% solution of conc. H2SO4 in Ac2O
and the synthesis of fully protected
L-gulosamine in
only three steps was carried out (Scheme 2). Due to the
inductive effect of two oxygen atoms at C1, the proton
of 2-OH is more acidic than the 3- or 4-OH. Regiose-
lective triflation of 5 with one equivalent of trifluo-
romethanesulfonic anhydride in pyridine provided the
2-OTf derivative as a single isomer. This result allowed
the one-pot synthesis of 6 (triflation and benzoylation),
which was subjected to nucleophilic substitution with
sodium azide to give 2-azido-2-deoxy-3,4-di-O-benzoyl-
b-
L
-gulopyranose 78 in 56% overall yield. The absolute
to afford the fully protected
in 94% yield.
L
-altropyranosyl sugar 13
structure was firmly secured through the X-ray single
crystal analysis.9 Typical acetolysis of 7 with trifluo-
roacetic acid and acetic anhydride only recovered the
starting material without isolation of any desired ring-
opening product 8. It is noted that extra addition of 1%
solution of conc. H2SO4 in Ac2O into the reaction
In conclusion, we have successfully developed a conve-
nient route to prepare the 1,6-anhydro-b- -ido, -gulo,
and -altro sugars and carried out an efficient synthesis
L
of fully protected
respectively.
L
-gulosamine 8 and
L
-altrose 13,
mixture afforded the fully protected -gulosamine 8 in
L
Scheme 2.

S.-C. Hung et al. / Tetrahedron Letters 42 (2001) 1321–1324
1323
Scheme 3.
Acknowledgements
8.10–7.97 (m, 4H, BzH), 7.62–7.36 (m, 6H, BzH), 5.60 (d,
J=1.5 Hz, 1H, H-1), 5.35–5.28 (m, 2H, H-2, H-3), 4.63
(t, J=4.8 Hz, 1H, H-5), 4.39 (d, J=8.0 Hz, 1H, H-6b),
4.15 (dd, J=7.1, 4.8 Hz, 1H, H-4), 3.85 (dd, J=8.0, 4.8
Hz, 1H, H-6a); 13C NMR (100 MHz, CDCl3) l 168.63
(C), 165.81 (C), 133.87 (CH), 133.72 (CH), 133.49 (CH),
130.19 (CH), 130.07 (CH), 129.92 (CH), 129.30 (C),
129.05 (C), 128.62 (CH), 128.57 (CH), 128.45 (CH), 99.07
(CH), 77.02 (CH), 75.37 (CH), 73.86 (CH), 71.16 (CH),
65.53 (CH2). Anal. calcd for C20H18O7: C, 64.86; H, 4.90.
Found: C, 64.92; H, 4.87. Compound 11: mp 148–149°C,
[h]3D0 +130 (c 1.0, CHCl3); IR (CHCl3) 1732, 1603, 1583
We thank Mr. Yuh-Sheng Wen for X-ray single crystal
structural analysis and the National Science Council of
Republic of China for financial support.
References
1. (a) Hung, S.-C.; Puranik, R.; Chi, F.-C. Tetrahedron Lett.
2000, 41, 77; (b) Hung, S.-C.; Wang, C.-C.; Thopate, S.
R. Tetrahedron Lett. 2000, 41, 3119.
1
cm−1; H NMR (400 MHz, CDCl3) l 7.99–7.95 (m, 4H,
2. Ogita, T.; Otake, N.; Miyazaki, Y.; Yonehara, H.; Mac-
farlane, R. D.; McNeal, C. J. Tetrahedron Lett. 1980, 21,
3203.
3. (a) Ko, S. Y.; Lee, A. W. M.; Masamune, S.; Reed, III,
L. A.; Sharpless, K. B.; Walker, F. J. Tetrahedron 1990,
46, 245; (b) Adinolfi, M.; Barone, G.; De Lorenzo, F.;
Iadonisi, A. Synlett 1999, 336; (c) Takahashi, H.; Hitomi,
Y.; Iwai, Y.; Ikegami, S. J. Am. Chem. Soc. 2000, 122,
2995.
BzH), 7.55–7.51 (m, 2H, BzH), 7.41–7.37 (m, 4H, BzH),
5.97 (t, J=8.8 Hz, 1H, H-3), 5.69 (d, J=2.0 Hz, 1H,
H-1), 5.19–5.15 (m, 2H, H-2, H-4), 4.87 (t, J=4.8 Hz,
1H, H-5), 4.39 (d, J=8.4 Hz, 1H, H-6b), 3.98 (dd,
J=8.4, 4.8 Hz, 1H, H-6a); 13C NMR (100 MHz, CDCl3)
l 165.58 (C), 165.10 (C), 133.68 (CH), 130.01 (CH),
129.84 (CH), 128.51 (CH), 116.77 (q, J=318 Hz), 99.43
(CH), 81.75 (CH), 74.95 (CH), 73.38 (CH), 69.33 (CH),
65.57 (CH2); HRMS (FAB, MH+) calcd for C21H18F3O9S
503.0624, found: 503.0638. Anal. calcd for C21H17F3O9S:
C, 50.20; H, 3.41. Found: C, 50.29; H, 3.50. Compound
4. Stack, R. J. FEMS Microbiol. Lett. 1987, 48, 83.
5. Zottola, M.; Rao, B. V.; Fraser-Reid, B. J. Chem. Soc.,
Chem. Commun. 1991, 969.
12: mp 122–123°C, [h]3D0 +266 (c 1.0, CHCl3); H NMR
1
6. Wolfrom, M. L.; Hanessian, S. J. Org. Chem. 1962, 27,
1800.
7. Paulsen, H.; Trautwein, W.-P.; Espinosa, F. G.; Heyns,
(400 MHz, CDCl3) l 8.01–7.99 (m, 4H, BzH), 7.53–7.49
(m, 2H, BzH) 7.40–7.24 (m, 4H, BzH), 5.66 (d, J=1.6
Hz, 1H, H-1), 5.50–5.43 (m, 2H, H-2, H-3), 5.47 (dd,
J=5.2, 2.4 Hz, 1H, H-5), 4.32 (ddd, J=9.6, 6.0, 3.6 Hz,
1H, H-4), 4.03 (dd, J=8.4 Hz, 1H, H-6a), 3.92 (dd,
J=8.4, 5.6 Hz, 1H, H-6b), 2.33 (d, J=6.0 Hz, 1H,
OH-4); 13C NMR (100 MHz, CDCl3) l 165.91 (C),
165.75 (C), 133.48 (CH), 133.41 (CH), 129.90 (CH),
129.84 (CH), 129.11 (C), 128.48 (CH), 128.41 (CH), 99.48
(CH), 76.85 (CH), 72.44 (CH), 70.64 (CH), 68.99 (CH),
65.72 (CH2); HRMS (FAB, MH+) calcd for C20H19O7:
371.1131, found: 371.1154. Anal. calcd for C20H18O7: C,
64.80; H, 4.90. Found: C, 64.59; H, 4.77.
K. Chem. Ber. 1967, 100, 2822.
8. The selected physical data of key compounds is listed.
Compound 7: 1H NMR (400 MHz, CDCl3) l 8.07 (m,
2H, BzH), 7.99 (m, 2H, BzH), 7.56 (m, 2H, BzH), 7.44
(m, 4H, BzH), 5.77 (dd, J=9.6, 5.3 Hz, 1H, H-3), 5.66
(ddd, J=9.6, 4.2, 0.8 Hz, 1H, H-4), 5.57 (d, J=2.2 Hz,
1H, H-1), 4.86 (t, J=4.2 Hz, 1H, H-5), 4.29 (d, J=8.2
Hz, 1H, H-6b), 4.19 (dd, J=5.3, 2.2 Hz, 1H, H-2), 3.82
(ddd, J=8.2, 4.2, 0.8 Hz, 1H, H-6a); 13C NMR (100
MHz, CDCl3) l 165.59 (C), 165.30 (C), 133.67 (CH),
130.00 (CH), 129.79 (CH), 128.83 (C), 128.55 (CH),
100.58 (CH), 72.59 (CH), 69.69 (CH), 69.44 (CH), 64.84
(CH2), 61.92 (CH). Compound 10: IR (CHCl3) 3067,
9. Crystal structure analysis of 7: colorless crystals from
chloroform/hexane, C20H17N3O6, fw=395.37, crystal di-
mensions: 0.41×0.31×0.19 mm3, crystal system: or-
thorhombic, space group: P21, unit-cell dimensions:
2974, 2906, 1602 cm−1 1H NMR (400 MHz, CDCl3) l
;

1324
S.-C. Hung et al. / Tetrahedron Letters 42 (2001) 1321–1324
,
a=10.773(3), b=7.283(4), c=11.9371(12) A, V=931.0(6)
mensions: 0.49×0.41×0.38 mm3, crystal system: or-
thorhombic, space group: P21, unit-cell dimensions: a=
3
A , Z=2, zcalcd=1.410 g cm−3, wavelength=0.7107 A,
F(000)=411.93, mu=0.11 mm−1, 2q(max)=50.0. The
deposit number at the Cambridge Crystallographic Data
Centre is CCDC 152187.
,
,
,
5.7578(6), b=16.016(3), c=11.9800(15) A, V=1100.9(3)
3
A , Z=2, zcalcd=1.516 g cm−3, wavelength=0.7093 A,
F(000)=515.95, mu=0.22 mm−1, 2q(max)=50.0. The
deposit number at the Cambridge Crystallographic Data
Centre is CCDC 152186.
,
,
10. Crystal structure analysis of 11: colorless crystals from
chloroform/hexane, C21H17F3O9S, fw=502.42, crystal di-
.
.