Efficient synthesis of L-altrose and L-mannose

Article abstract of DOI:10.1016/S0040-4039(00)00363-4

Two convenient routes for the synthesis of L-altrose and L-mannose from 1,2:3,5-di-O-isopropylidene-β-L-idofuranose in four and six steps via the stereoselective hydroboration and hydrogenation of olefins as key steps are described here, respectively. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00363-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 3119–3122
Efficient synthesis of L-altrose and L-mannose
Shang-Cheng Hung,∗ Cheng-Chung Wang and Shankar R. Thopate
Institute of Chemistry, Academia Sinica, Nankang, Taipei 11529, Taiwan
Received 20 December 1999; revised 25 January 2000; accepted 25 February 2000
Abstract
Two convenient routes for the synthesis of L-altrose and L-mannose from 1,2:3,5-di-O-isopropylidene-β-L-
idofuranose in four and six steps via the stereoselective hydroboration and hydrogenation of olefins as key steps
are described here, respectively. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: carbohydrates; glycosides; L-altrose; L-mannose.
L-Altropyranosyl and L-mannopyranosyl units are structural elements of several naturally occurring
products, as outlined in Scheme 1. L-Altrose is a component of the extracellular polysaccharide from
Butyrivibrio fibrisolvens strain CF3.1 The O-specific polysaccharide of the bacterium Proteus mirabilis,
a human opportunistic pathogen causing urinary tract infections, contain L-altropyranouronic acid as
a new component of O-antigens.2 L-Mannopyranosides had been found in the sugar units of steroid
glycosides3 and their phenol derivatives are potent substrates for determining the α-L-mannosidase
activity of commercial naringinase.4
Scheme 1.
Approaches for the synthesis of L-altrose have been reported including the asymmetric Sharpless
epoxidation of olefins followed by ring opening,5 intramolecular Tishchenko reactions of protected
hexos-5-uloses6 and bromination of ∆4-uronate followed by a three-step conversion.7 Some efforts had
also been made toward the L-mannose comprising the asymmetric hetero Diels–Alder reaction followed
by stereoselective hydroboration8 and the applications of enantioselective Sharpless epoxidation5 as well
as dihydroxylation9 of olefins. In association with our interest in the synthesis of biologically important
L-hexoses, we have explored herein two short routes for the synthesis of L-altrose and L-mannose,
respectively.
∗
Corresponding author.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00363-4
tetl 16646

3120
Scheme 2 illustrates an efficient synthesis of L-altrose from 1,2:3,5-di-O-isopropylidene-β-L-
idofuranose 1 in four steps. The starting material 1, generated from diacetone α-D-glucose in three
steps,10 underwent orthogonal isopropylidene rearrangement with a solution of 2,2-dimethoxypropane
and acetone in the presence of catalytic amount of (±)-camphorsulfonic acid at room temperature to
provide 1,2:5,6-di-O-isopropylidene-β-L-idofuranose 3 as a white solid (42% after recrystallization
from hexane) and a mixture of 2 and unreacted 1 in ca. 52% yield. This mixture can be re-utilized
under the same conditions and similar results are obtained. Epimerisation of 3 at C-4 into 1,2:5,6-
di-O-isopropylidene-β-L-altrofuranose 5 could be carried out by sequential elimination of H2O and
stereoselective hydroboration via the olefin 4 as an intermediate. Diethylaminosulfur trifluoride
(DAST)11 and pyridine were consecutively added to a solution of 3 in dichloromethane at 0°C under
nitrogen. The mixture was subjected to distillation by the Kugelhror apparatus at 100°C under 0.12
mmHg to give the olefin 412 (51%) which was treated with borane reagent followed by oxidative
work-up to provide 512 as a single isomer in 78% yield. The high stereoselectivity is perhaps due to
the steric hindrance of a 5,5-cis-fused ring configuration, forming the 3-hydroxy group toward up-face.
Acidic hydrolysis of 5 in the presence of Amberlite-120 resin (H+ form) afforded the desired L-altrose
in quantitative yield. Comparison of our data with the literature report13 revealed identity with respect to
1H and 13C NMR spectra.
Scheme 2.
The preparation of L-mannose from 3 in five steps is summarized in Scheme 3. The key step involving
the inversion of chiral centers in 3 at C-3 and C-4 positions could be achieved by syn-reduction of the
enol acetate 7. Oxidation of 3 with PDC and acetic anhydride14 led to the ketone 6 which underwent
enolization in pyridine and acetic anhydride to furnish the enol acetate 712 (81% from 3 in two steps).
Stereoselective hydrogenation in the presence of 10% Pd/C as the catalyst provided 3-O-acetyl-1,2:5,6-
di-O-isopropylidene-β-L-mannofuranose 812 in 74% yield. The highly stereoselective syn-addition of
hydrogen molecule with 3-endo double bond occurring from less-hindered side is perhaps induced by the
cis-fused ring junction. Similar transformation of 3-O-acetyl-1,2:5,6-di-O-isopropylidene-α-D-erythro-
hex-3-endofuranose into 1,2:5,6-di-O-isopropylidene-α-D-gulofuranose via the NaBH4 reduction had

3121
been reported in 34% yield.15 The yield can be improved by the hydrogenation reaction. Deacetylation
of 8 with sodium methoxide in methanol obtained 9 (98%) which was hydrolyzed in acidic media to
1
afford the target L-mannose in quantitative yield. The H and 13C NMR spectra are identical with the
literature report.16
Scheme 3.
In conclusion, two convenient routes for the synthesis of L-altrose, L-mannose and their furanosyl
derivatives are successfully developed here, respectively. The application of these carbohydrates for the
synthesis of biologically important oligosaccharides is currently under investigation.
Acknowledgements
We thank Prof. Sunney I. Chan for his helpful discussions and the National Science Council of
Republic of China for financial support.
References
1. Stack, R. J. FEMS Microbiol. Lett. 1987, 48, 83.
2. Swierzko, A. S.; Shashkov, A. S.; Senchenkova, S. N.; Toukach, F. V.; Ziolkowski, A.; Cedzynski, M.; Paramonov, N. A.;
Kaca, W.; Knirel, Y. A. FEBS Lett. 1996, 398, 297.
3. Kubelka, W. Phytochemistry 1974, 13, 1805.
4. Esaki, S.; Ohishi, A.; Katsumata, A.; Sugiyama, N.; Kamiya, S. Biosci. Biotech. Biochem. 1993, 57, 2099.
5. Ko, S. Y.; Lee, A. W. M.; Masamune, S.; Reed III, L. A.; Sharpless, K. B.; Walker, F. J. Tetrahedron 1990, 46, 245.
6. Adinolfi, M.; Barone, G.; De Lorenzo, F.; Iadonisi, A. Synlett 1999, 336.
7. Bazin, H. G.; Wolff, M. W.; Linhardt, R. J. J. Org. Chem. 1999, 64, 144.
8. Tietze, L. F.; Montenbruck, A.; Schneider, C. Synlett 1994, 509.
9. Harris, J. M.; Keranen, M. D.; O’Doherty, G. A. J. Org. Chem. 1999, 64, 2982.
10. Hung, S.-C.; Puranik, R.; Chi, F.-C. Tetrahedron Lett. 2000, 41, 77.
11. Tewson, T. J.; Welch, M. J. J. Org. Chem. 1978, 43, 1090.
12. The selected physical data of key compounds is listed. Compound 4: IR (CHCl3) ν 1669 (m) cm−1; 1H NMR (400 MHz,
CDCl3) δ 6.05 (d, J=5.1 Hz, 1H, H-1), 4.27 (dd, J=5.1, 2.2 Hz, 1H, H-2), 5.23 (d, J=2.2 Hz, 1H, H-3), 4.57 (t, J=6.8 Hz,
1H, H-5), 4.12 (dd, J=8.3, 6.8 Hz, 1H, H-6), 3.91 (dd, J=8.3, 6.8 Hz, 1H, H-6), 1.43 (s, 3H, C-CH3), 1.41 (s, 3H, C-CH3),
1.39 (s, 3H, C-CH3), 1.37 (s, 3H, C-CH3); 13C NMR (75 MHz, CDCl3) δ 159.76 (C), 112.26 (C), 110.29 (C), 106.50 (CH),
99.42 (CH), 83.33 (CH), 71.44 (CH), 67.21 (CH2), 28.12 (CH3), 27.81, (CH3), 26.09 (CH3), 25.48 (CH3). Compound 5:
25
1
[α]D =−17.7 (c 1.0, CHCl3); mp=87–88°C; IR (CHCl3) ν 3390 (s) cm−1; H NMR (400 MHz, CDCl3) δ 5.85 (d, J=3.9

3122
Hz, 1H, H-1), 4.54 (d, J=3.9 Hz, 1H, H-2), 4.40 (t, J=2.5 1H, H-3), 4.23 (ddd, J=9.4, 6.1, 5.0 Hz, 1H, H-5), 4.09 (dd, J=8.7,
6.1 Hz, 1H, H-6), 3.92 (dd, J=8.7, 5.0 Hz, 1H, H-6), 3.77 (dd, J=9.4, 2.5 Hz, 1H, H-4), 2.96 (d, J=3.9 Hz, 1H, OH), 1.49 (s,
3H, C-CH3), 1.41 (s, 3H, C-CH3), 1.33 (s, 3H, C-CH3), 1.30 (s, 3H, C-CH3); 13C NMR (100 MHz, CDCl3) δ 112.76 (C),
109.71 (C), 105.59 (CH), 88.27 (CH), 87.05 (CH), 76.68 (CH), 75.56 (CH), 67.62 (CH2), 27.04 (CH3), 26.90 (CH3), 26.10
(CH3), 25.31 (CH3). Anal. calcd for C12H20O6: C,55.37;H,7.74, found: C,55.68; H,7.79. Compound 7: [α]2D8=−41.5 (c 1.0,
CHCl3); IR (neat) ν 1751 (s), 1623 (m) cm−1; 1H NMR (CDCl3, 400 MHz) δ 6.02 (d, J=5.4 Hz, 1H, H-1), 5.38 (d, J=5.4
Hz, 1H, H-2), 4.67 (t, J=7.0 Hz, 1H, H-5), 4.10 (dd, J=8.3, 7.0 Hz, 1H, H-6), 3.99 (dd, J=8.3, 7.0 Hz, 1H, H-6), 2.19 (s, 3
H), 1.46 (s, 3 H), 1.43(s, 3 H), 1.43(s, 3 H), 1.37(s, 3 H); 13C NMR (CDCl3, 100 MHz) δ 168.42 (C), 144.85 (C), 128.94
(C), 113.27 (C), 110.39 (C), 103.86 (CH), 81.03 (CH), 68.92 (CH), 65.73 (CH2), 27.88 (CH3), 27.80 (CH3), 25.68 (CH3),
20.48 (CH3). Compound 8: [α]3D0=+26.6 (c 1.0, CHCl3); IR (neat) ν 1750 cm−1; 1H NMR (CDCl3, 400 MHz) δ 5.70 (d,
J=4.1 Hz, 1H, H-1), 5.16 (t, J=5.8 Hz, 1H, H-3), 4.74 (dd, J=5.8, 4.1 Hz, 1H, H-2), 4.50 (dt, J=8.7, 6.0 Hz, 1H, H-5), 4.07
(dd, J=8.7, 6.0 Hz, 1H, H-6), 4.01 (dd, J=8.7, 6.0 Hz, 1H, H-4), 3.97 (dd, J=8.7, 6.0 Hz, 1H, H-6), 2.12 (s, 3H), 1.54 (s, 3H),
1.34 (s, 3H), 1.31 (s, 3H); 13C NMR (CDCl3, 75 MHz) δ 170.15 (C), 114.63 (C), 109.57 (C), 104.68 (CH), 79.44 (CH),
73.49 (CH), 71.11 (CH), 67.18 (CH2), 26.90 (CH3), 26.73 (CH3), 25.56 (CH3), 20.74 (CH3). Compound 9: [α]3D0=+3.4 (c
1.1, CHCl3); IR (neat) ν 3502 (br) cm−1; 1H NMR (CDCl3, 400 MHz) δ 5.68 (d, J=4.2 Hz, 1H, H-1), 4.65 (dd, J=5.8, 4.2
Hz, 1H, H-2), 4.55 (dt, J=8.7, 6.0, 1H, H-5), 4.28 (t, J=5.8, 1H, H-3), 4.11 (dd, J=8.7, 6.0 Hz, 1H, H-6), 3.96 (dd, J=8.7,
6.0 Hz, 1H, H-6), 3.83 (dd, J=8.7, 5.8 Hz, 1H, H-4), 3.00–2.80 (bs, 1H, OH) 1.57 (s, 3H), 1.41 (s, 3H), 1.38 (s, 3H), 1.35
(s, 3H); 13C NMR (CDCl3, 75 MHz) δ 114.77 (C), 109.67 (C), 105.06 (CH), 81.87 (CH), 80.13 (CH), 73.56 (CH), 70.06
(CH), 67.38 (CH2), 26.99 (CH3), 26.79 (CH3), 25.37 (CH3).
1
13. The Aldrich Library of 13C and H FT NMR Spectra; Pouchert, C. J.; Behnke, J., Ed.; Aldrich Chemical Company, Inc.,
USA, Vol. I (1), p. 301B.
14. Reckendorf, W. M. Chem. Ber. 1969, 102, 1071.
15. Reckendorf, W. M. Methods in Carbohydrate Chemistry 1972, 6, 129.
16. The Aldrich Library of 13C and 1H FT NMR Spectra; Pouchert, C. J.; Behnke, J., Eds.; Aldrich Chemical Company, Inc.,
USA, Vol. I (1), p. 299B.