Novel synthesis of 1,2:3,5-di-O-isopropylidene-β-L-idofuranoside and its derivatives at C6

Article abstract of DOI:10.1016/S0040-4039(99)02004-3

An efficient synthesis of 1,2:3,5-di-O-isopropylidene-β-L-idofuranoside and its derivatives at C6 from diacetone α-D-glucose employing the stereoselective hydroboration and hydrogenation as key steps is described here.

Full text of DOI:10.1016/S0040-4039(99)02004-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 77–80
Novel synthesis of 1,2:3,5-di-O-isopropylidene-β-L-
idofuranoside and its derivatives at C6
Shang-Cheng Hung,a,∗ Ramachandra Puranik a and Fa-Chen Chi a,b
aInstitute of Chemistry, Academia Sinica, Nankang, Taipei 11529, Taiwan
bDepartment of Chemistry, National Tsing Hua University, Hsinchu 30043, Taiwan
Received 17 September 1999; revised 13 October 1999; accepted 18 October 1999
Abstract
An efficient synthesis of 1,2:3,5-di-O-isopropylidene-β-L-idofuranosideand its derivatives at C6 from diacetone
α-D-glucose employing the stereoselective hydroboration and hydrogenation as key steps is described here. © 1999
Elsevier Science Ltd. All rights reserved.
Keywords: hydroboration; hydrogenation; carbohydrates; L-idoses.
L-Idopyranosyl units are important structural elements of several naturally biological oligosac-
charides. Glycosaminoglycans, e.g. heparin, heparan sulfate, and dermatan sulfate, containing L-
idopyranosyluronate (Scheme 1) as a typical component play significant roles in diverse biological
processes, including blood coagulation, cell growth control, inflammation, wound healing, virus infec-
tion, tumor metastasis, and diseases of the nervous system.1 The first chemical synthesis and structural
modification of an antithrombin-binding pentasaccharide has been carried out by Sinaÿ2 and others.3
Aminoglycoside antibiotics having specific binding to the A-site of prokaryotic 16S rRNA interfere with
mRNA translation and ultimately lead to bacterial cell death.4 The structurally related aminoglycosides,
neomycin B, paromomycin, and lividomycin A, contain 2,6-diamino-2,6-dideoxy-L-idopyranoside as
the D-ring. Elegant work in the modification of this D-ring as 6-amino-6-deoxy-L-idopyranoside for
Scheme 1.
∗
Corresponding author.
0040-4039/00/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02004-3

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the study of the structure–activity relationship between carbohydrates and RNA presents remarkable
antibacterial activity, as reported by Wong and co-workers.5 Some diterpene glycosides isolated from
Aster spathulifolius Maxim. also contain unusual 6-deoxy-L-idopyranosides.6 However, their biological
activity remains unclear.
Most synthetic methodologies of L-ido sugars begin with D-gluco compounds and involve the selec-
tive inversion of configuration at C5. Several approaches had been done, including the nucleophilic
displacements of a 5-sulfonate or mesylate group in D-glucofuranoside7 or D-glucofuranuronic acid
derivatives;8 diastereoselective hydroboration of 6-exo-glucal derivatives;5,9 radical reduction of acetyl-
ated 5-bromouronates;10 and others.11 These methodologies may, however, afford two diastereoisomers
needed to be separated or require too many steps to accomplish the inversion at C5. The route we have
explored herein is based on the model of isopropylidene fixation on 3,5-dihydroxyl groups of 1,2-O-
isopropylidene-α-D-glucofuranoside to form a cis–anti–cis-tricyclic fused compound 2. It is predicted to
induce higher diastereoselectivity of L-ido configuration from the less-hindered side in the hydroboration
or hydrogenation of 5-exo-double bond.
An efficient synthesis of L-ido sugars from diacetone α-D-glucose is indicated in Scheme 2. Treat-
ment of diacetone α-D-glucose with triphenylphosphine and NBS afforded 6-bromo-1,2:3,5-di-O-
isopropylidene-α-D-glucofuranoside 112 (75%) in one pot via a combination of isopropylidene re-
arrangement and regio-selective bromination. Elimination of HBr with DBU furnished the enol ether
213 in 84% yield. Hydroboration followed by oxidative work-up provided 1,2:3,5-di-O-isopropylidene-
β-L-idofuranoside 314 (90%) as a single adduct. The L-form configuration was determined by the X-ray
single crystal structural analysis of 6-tosyl-1,2:3,5-di-O-isopropylidene-β-L-idofuranoside 5 (Fig. 1).15
The stereo ORTEP drawing illustrates the C4–O4 and C3–C2 bonds are at the axial- and equatorial-
positions, respectively. Due to the steric effect, the addition of borane with 5-exo double bond occurs
from the α-face, forming the substituted group (CH2OH) at the equatorial position of C5 (L-form).
Scheme 2.

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Figure 1. The stereo ORTEP drawing of 5
Functional group transformation of 3 with DAST and TsCl followed by NaN3 gave 413 (55%) and 613
(74% in two steps), respectively. Hydrogenation of 2 in the presence of Pd/C led to 6-deoxy-1,2:3,5-di-O-
isopropylidene-β-L-idofuranoside 713 as a single diastereoisomer in 88% yield. Super hydride reduction
of 5 furnished the same adduct 7. It indicates that the methyl group of 7 is at the equatorial-position. The
high stereoselectivity is perhaps induced by the steric hindrance in β-face.
In conclusion, a short synthesis of 1,2:3,5-di-O-isopropylidene-β-L-idofuranoside and its derivatives at
C6 is successfully developed here. 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 discussion, Dr. Kuan-Jiuh Lin for X-ray single crystal
structural analysis, and the National Science Council for financial support.
References
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80
12. Hodosi, G.; Podányi, B.; Kuszmann, J. Carbohydr. Res. 1992, 230, 327.
13. The selected physical data of new compounds is listed. Compound 2: 1H NMR (400 MHz, CDCl3) δ 5.98 (d, J=3.7 Hz,
1H, H-1), 4.76 (d, J=0.8 Hz, 1H, H-6), 4.69 (d, J=0.8 Hz, 1H, H-6), 4.56 (d, J=3.7 Hz, 1H, H-2), 4.37 (d, J=2.3 Hz, 1H,
H-3), 4.34 (d, J=2.3 Hz, 1H, H-4), 1.52 (s, 3H, methyl), 1.47 (s, 3H, methyl), 1.40 (s, 3H, methyl), 1.33 (s, 3H, methyl);
HRMS (FAB, M+) calcd for C12H18O5: 242.1154; found: 242.1152. Compound 4: 1H NMR (400 MHz, CDCl3) δ 5.94 (d,
J=3.6 Hz, 1H, H-1), 4.66 (ddd, J=48.2, 9.8, 4.2 Hz, 1H, H-6), 4.55 (ddd, J=48.2, 7.0, 4.2 Hz, 1H, H-6), 4.50 (d, J=3.6
Hz, 1H, H-2), 4.37–4.30 (m, 2H, H-3, H-5), 3.96 (t, J=2.0 Hz, 1H, H-4), 1.45 (s, 3H, methyl), 1.44 (s, 3H, methyl), 1.39
(s, 3H, methyl), 1.29 (s, 3H, methyl); anal. calcd for C12H20O5F: C, 54.96; H, 7.25; found: C, 54.89; H, 7.36. Compound
6: 1H NMR (400 MHz, CDCl3) δ 5.93 (d, J=3.6 Hz, 1H, H-1), 4.49 (d, J=3.6 Hz, 1H, H-2), 4.31 (d, J=2.2 Hz, 1H, H-3),
4.14 (ddd, J=8.1, 4.5, 2.2, Hz, 1H, H-5), 3.92 (t, J=2.2 Hz, 1H, H-4), 3.58 (dd, J=12.8, 8.1 Hz, 1H, H-6), 3.36 (dd, J=12.8,
4.5 Hz, 1H, H-6), 1.48 (s, 3H, methyl), 1.45 (s, 3H, methyl), 1.40 (s, 3H, methyl), 1.31 (s, 3H, methyl); HRMS (FAB,
1
MH+) calcd for C12H20O5N3: 286.1402; found: 286.1405. Compound 7: H NMR (400 MHz, CDCl3) δ 5.89 (d, J=3.6
Hz, 1H, H-1), 4.43 (d, J=3.6 Hz, 1H, H-2), 4.12 (d, J=1.5 Hz, 1H, H-3), 4.07 (dq, J=6.5, 1.5, Hz, 1H, H-5), 3.78 (t, J=1.5
Hz, 1H, H-4), 1.42 (s, 3H, methyl), 1.37 (s, 3H, methyl), 1.32 (s, 3H, methyl), 1.27 (d, J=6.5 Hz, 3H, methyl), 1.25 (s, 3H,
methyl); HRMS (FAB, MH+) calcd for C12H21O5: 245.1388; found: 245.1381.
14. Hughes, N. A.; Munkombwe, N. M. Carbohydr. Res. 1982, 101, 221.
15. The deposited number at the Cambridge Crystallographic Data Centre is CCDC 133558.