A concise synthesis of 3-hydroxy-4-β-glucopyranosyl) benzoate: A new route to β-C-aryl glycosides

Article abstract of DOI:10.1055/s-1999-3165

A synthesis of specifically substituted β-C-aryl glycosides is described. The aromatic moiety is built up starting from the easily available 2,3,4,6-tetra-O-benzyl-D-gluconolactone with a benzoannulation reaction as a key step.

Full text of DOI:10.1055/s-1999-3165

LETTER
1241
A Concise Synthesis of 3-Hydroxy-4-(b-glucopyranosyl) Benzoate: A New
Route to b-C-Aryl Glycosides
Claudio Fuganti, Stefano Serra*
Dip. di Chimica del Politecnico, Centro CNR per la Chimica delle Sostanze Organiche Naturali,Via Mancinelli 7, 20131 Milano, Italy
Fax: 39 2 23993080. E-mail: lab545@dept.chem.polimi.it
Received 12 May 1999
with triethylsilane (3 equiv) and boron trifluoride (3
Abstract: A synthesis of specifically substituted b-C-aryl glyco-
equiv)9 to afford exclusively the b-linked propargylic al-
sides is described. The aromatic moiety is built up starting from the
cohol 3 in 65% yield. Regioselective reduction of the tri-
easily available 2,3,4,6-tetra-O-benzyl-D-gluconolactone with a
ple bond with sodium bis-(2-methoxyethoxy)aluminium
hydride10 (1.6 eq. based on aluminium) gave us the trans
allylic alcohol in 86% yield, which was oxidized with
MnO2 (10 equiv) in refluxing CHCl3 to the aldehyde 4 in
75% yield.11 Its conversion into 6-glucopyranose-3-
ethoxycarbonyl-3,5-exadienoic acid 5 was performed by
Wittig reaction (Scheme 2) with triphenyl-(a-carbethoxy-
b-carboxyethyl)phosphonium betaine.12
benzoannulation reaction as a key step.
Key words: annulation, cyclization, carbohydrates, glycosides,
phenols
C-Aryl glycosides are an important subclass of C-glyco-
sides.1 Several products containing C-aryl glycosidic link-
age were isolated from natural sources and their relevant
biological interest2 prompted our study in this field. Many
different synthetic approaches have been developed
recently3 and in most cases these methods couple a carbo-
hydrate derivative with a suitable aryl moiety. Since ar-
enes bearing electron-withdrawing groups lack reactivity,
some alternate procedures in which the aromatic ring is
constructed from a pre-existing C-glycoside have been re-
ported.4 Here, we report a concise preparation of 3-hy-
droxy-4-(b-glucopyranosyl) benzoic acid ester 6 using the
benzoannulation reaction of 3-alkoxycarbonyl-3,5-hexa-
dienoic acids.5 We have shown that the latter process is
very flexible,6 giving benzoannulated phenols bearing a
benzylic stereocentre starting from g-chiral-a,b-unsatur-
ated aldehydes.7 In order to extend this cyclization to the
synthesis of C-aryl-glycosides, we prepared the suitable
g-glucopyranose-a,b-unsaturated aldehyde 4 (Scheme 1).
Reagents and conditions: e) triphenyl-(a-carbethoxy-b-carboxy-
ethyl)phosphonium betaine, CHCl3 reflux 10 h; f) ClCO2Et 1.5 equiv,
Et3N 2 equiv, r.t. 15 min; g) NaOH/EtOH, 10 min. then HCl aq
Scheme2
Cyclization of 5 in THF solution with ClCO2Et, followed
by addition of Et3N, gave the phenol 6 together with a
small amount of its carboxyethyl derivative. Quick treat-
ment of the latter mixture with an excess of ethanolic
NaOH (2 eq.) gave the b-C-glycoside 6 in 91% yield.13
Many different lactones can be used in the preparation of
C-glycosyl compounds by the Kraus method. Thus, our
synthetic approach may be applicable for the preparation
of different C-aryl-glycosides showing the 3-hydroxy-4-
(gluco) benzoate ester substitution pattern. This kind of
compound has been already used as starting material for
the synthesis of some pyranonaphthoquinone antibiot-
ics.14 Moreover, the preparation of 6 itself might hold
some general significance in the preparation of the C-
linked glycopeptides, a class of compounds of current in-
terest.15 Indeed, simple functional group manipulation and
C-2 chain elongation should allow the conversion of the
ester 6 into 3-hydroxy-4-(gluco) phenyalanine, a product
conceivably not so directly accessible through the usual
C-arylation methods.
Reagents and conditions: 2+1 THF, -78 °C, 30 min then 0 °C, 1 h;
b) Et3SiH, BF3.Et2O, CH2Cl2, to -78 °C at r.t, 2 h then H2O; c) RED-
Al, Et2O, 0 °C, 1 h; d) MnO2, CHCl3, reflux, 4 h.
Scheme 1
The easy available 2,3,4,6-tetra-O-benzyl-D-gluconolac-
tone 18 was condensed with the lithium salt of protected
propynol 2 to give an anomeric mixture of the related al-
cohol in almost quantitative yield. The latter was treated
Synlett 1999, No. 8, 1241–1242 ISSN 0936-5214 © Thieme Stuttgart · New York

1242
C. Fuganti, S. Serra
LETTER
(12) For the preparation of this betaine see: Hudson, R. F.;
Acknowledgement
Chopard, P. A. Helv. Chim. Acta 1963, 46, 2178.
(13) Ethyl chloroformate (4 mmol) was added to a THF solution of
acid 5 (2 mmol, 0.1 M) and then Et3N (6 mmol) was added
slowly, while the temperature was kept under 20 °C. The
reaction mixture was stirred for 10 min., was treated with an
excess of 5% aq, HCl and was extracted with ethyl acetate.
The organic phase was concentrated in vacuo, to give a
residual mixture of 6 and its carboxyethyl derivative. The
latter was treated with ethanolic NaOH (6 mmol) at room
temperature for 10 min. The mixture was diluted with an
excess of 5% aq HCl and was extracted with ethyl acetate. The
organic phase was dried (Na2SO4), and was concentrated in
vacuo. The residue was chromatographed on a silica gel
column eluted with hexane-ethyl acetate (10:1-2:1) to give in
91% yield the phenol 6 with the following analytical data:
Anal. Calcd for C43H44O8: C, 75.02; H, 6.39. Found: C, 74.95;
H, 6.40. mp 123-124 °C (hexane); [a]D20 = -15.8° (c 1,
CHCl3); 1H NMR (400 MHz, CDCl3) d 1.41 (3H, t,
J = 7.2Hz), 3.59 (1H, dt, J = 9.7, 2Hz), 3.66-3.82 (4H, m),
3.84-3.94 (2H, m), 4.38 (2H, q, J = 7.2Hz), 4.42-4.52 (3H, m),
4.54-4.62 (2H, m), 4.85 (1H, d, J = 10.9Hz), 4.87-4.97 (2H,
m), 6.93-7.00 (2H, m), 7.12-7.40 (20H, m), 7.56 (1H, dd,
J = 7.8, 1.6Hz), 7.6 (1H, d, J = 1.6Hz); MALDI 710.3 (M+-
1+Na), 726.4 (M+-1+K); FT-IR (neat): n (cm-1) 697, 737,
1093, 1216, 1288, 1360, 1455, 1500, 1578, 1716, 2904, 3336.
(14) Tatsuta, K.; Ozeki, H.; Yamaguchi, M.; Tanaka, M.; Okui, T.;
Tetrahedron Lett. 1990, 31, 5495.
We thank MURST for partial financial support.
References and Notes
(1) For a review on the synthesis of C-glycosides see: Levy, D. E.;
Tang, C. in The chemistry of C-Glycosides (Tetrahedron
Organic Chemistry Series), Vol. 13, Pergamon Press 1995;
Postema, M. H. D.; Tetrahedron 1992, 48, 8545.
(2) Hacksell, U.; Daves, G. D.; Progress Med. Chem. 1985, 22, 1.
(3) Jaramillo, C.; Knapp, S.; Synthesis 1994, 1.
(4) Schmidt, R. R.; Effenberger, G.; Liebigs Ann. Chem. 1987,
825; Kozikowski, A. P.; Cheng, X. M.; J. Chem. Soc., Chem.
Commun. 1987, 680; Kraus, G. A.; Shi, J.; J. Org. Chem.
1990, 55, 4922; Paetsch, D.; Dötz, K. H.; Tetrahedron Lett.
1999, 40, 487.
(5) Brenna, E.; Fuganti, C.; Perozzo, V.; Serra, S.; Tetrahedron
1997, 53, 15029; Brenna, E.; Fuganti, C.; Serra, S.; J. Chem.
Soc., Perkin Trans. 1 1998, 901.
(6) Fuganti, C.; Serra, S.; Tetrahedron Lett. 1998, 39, 5609;
Fuganti, C.; Serra, S.; J. Chem. Res. (S) 1998, 638; J. Chem.
Res. (M) 1998, 2769.
(7) Fuganti, C.; Serra, S.; Synlett 1998, 1252.
(8) Kuzuhara, H.; Fletcher, H. G.; J. Org. Chem. 1967, 32, 2531.
(9) Kraus, G. A.; Molina, M. T.; J.Org. Chem. 1988, 53, 752.
(10) Denmark, S. E.; Jones, T. K.; J. Org. Chem. 1982, 47, 4595.
(11) Compound 4: Anal. Calcd for C37H38O6: C, 76.84; H, 6.57.
Found: C, 76.65; H, 6.55. mp. 67-69 °C; [a]D20 = -38.6° (c 2,
CHCl3); 1H NMR (400 MHz, CDCl3) d 3.36 (1H, t,
J = 9.2Hz), 3.51 (1H, dt, J = 3, 9.7Hz), 3.63-3.80 (4H, m),
4.01 (1H, ddd, J = 1.5, 4.3, 9.7Hz), 4.53-4.65 (4H, m), 4.82-
4.89 (2H, m), 4.94 (2H, s), 6.37 (1H, ddd, J = 1.5, 8, 15.7Hz),
6.70 (1H, dd, J = 4.3, 15.7Hz), 7.20-7.45 (20H, m), 9.39 (1H,
d, J = 8Hz); MALDI 600.2 (M+-1+Na), 616.1 (M+-1+K); FT-
IR (neat): n (cm-1) 700, 755, 1065, 1095, 1360, 1454, 1497,
1688, 2863, 3030.
(15) Lowary, T.; Meldal, M.; Helmboldt, A.; Vasella, A.; Bock, K.
J. Org. Chem. 1998, 63, 9657.
Article Identifier:
1437-2096,E;1999,0,08,1241,1242,ftx,en;G13999ST.pdf
Synlett 1999, No. 8, 1241–1242 ISSN 0936-5214 © Thieme Stuttgart · New York