Total Synthesis of Floridoside

Abstract

The native floridoside [2′-O-(α-d-galactopyranosyl)-glycerol], isolated from the red marine alga Rhodymenia palmata, has demonstrated a potent immunostimulating activity. In order to carry out further biological investigations, the synthesis of this compound appeared necessary and is reported here, for the first time.

floridoside - 2′-O-(α-d-galactopyranosyl)glycerol - glycosylation - bioactive glycosides - antitumor agent

References and Notes

<A NAME="RG06107ST-1">1</A> Colin H. Guéguen E. C. R. Hebd. Seances Acad. Sci  1930,  191:  163 

<A NAME="RG06107ST-2">2</A> Putman EW. Hassid WZ. J. Am. Chem. Soc.  1954,  76:  2221 

<A NAME="RG06107ST-3">3</A> Simon-Colin C., Kervarec N., Pichon R., Deslandes E.; Carbohydr. Res.; 2002, 337: 279

<A NAME="RG06107ST-4">4</A> Bean RC. Hassid MM. J. Biol. Chem.  1955,  212:  411 

<A NAME="RG06107ST-5">5</A> Kirst GO. Bisson MA. Aust. J. Plant Physiol.  1979,  6:  539 

<A NAME="RG06107ST-6">6</A> Ben-Amote A. Avron M. Ann. Rev. Microbiol.  1983,  37:  95 

<A NAME="RG06107ST-7">7</A> Reed RH. In Biology of the Red Algae   Cole KM. Sheath RG. Cambridge University Press; Cambridge: 1990.  p.147-170  

<A NAME="RG06107ST-8">8</A> Galli U. Immunol. Today  1993,  14:  480 

<A NAME="RG06107ST-9">9</A> Ohlsson J. Magnusson G. Carbohydr. Res.  2000,  329:  49 

<A NAME="RG06107ST-10">10</A> Schmidt RR. Angew. Chem., Int. Ed. Engl.  1986,  25:  212 

<A NAME="RG06107ST-11">11</A> Schmidt RR. Michel J. Roos M. Liebigs Ann. Chem.  1984,  1343 

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Melting points were determined in capillary tubes with a Büchi apparatus and are uncorrected. Optical rotations are measured at 20-25 °C with Perkin-Elmer 341 polarimeter. ¹H NMR and ¹³C NMR spectra were recorded at 25 °C with a Bruker DPX400 spectrometer operating at 400 and 100 MHz, respectively. Assignments were based on homo- and heteronuclear correlations using supplier’s software. Flash column chromatography was performed on silica gel (E. Merck, 40-63 µm). Microanalyses were performed by the department of microanalysis of CNRS (ICSN, Gif sur Yvette, France).

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General Procedure for the Glycosylation A mixture of trichloroacetimidate (600 mg, 0.75 mmol), cis-1,3-O-benzylideneglycerol (315 mg, 1.75 mmol) and activated powdered MS 4 Å in anhyd CH₂Cl₂ (10 mL) was stirred for 1 h at r.t. under dry N₂, then cooled to 0 °C. A solution of TMSOTf in toluene (1 M, 131 µL, 15%) was added, and the mixture was stirred for 30 min at r.t., then was quenched with Et₃N, filtered and concentrated. Flash silica gel chromatography (hexane-EtOAc = 3:1, containing 0.1% of Et₃N) gave 7 (125 mg, 20%) and 6 (400 mg, 65%).
cis -1′,3′- O -Benzylidene-2′- O -(2,3,4,6-tetra- O -benzyl-α-d -galactopyranosyl)glycerol ( 6)
[α]_D +7 (c 1.0, CHCl₃). ¹H NMR (CDCl₃): δ = 7.40-7.10 (m, 25 H, arom. H), 5.57 (s, 1 H, PhCH), 5.10 (d, 1 H, J _1,2 = 2.8 Hz, H-1), 5.00-4.53 (m, 6 H, PhCH₂), 4.48-4,38 (m, 5 H, PhCH₂, OCH₂, OCH), 4.20-4.13 (m, 1 H, H-5), 4.10-3.90 (m, 5 H, H-2, H-3, H-4, OCH₂), 3.58-3.49 (m, 2 H, H-6a, H-6b). ¹³C NMR (CDCl₃): δ = 138.9-126.3 (arom. C), 101.4 (PhCH), 96.7 (C-1), 78.8 (C-4), 76.7 (C-2), 75.1 (C-3), 74.8-73.0 (PhCH₂), 70.2 (OCH₂), 69.6 (OCH), 69.5 (C-5), 69.1 (C-6), 68.5 (OCH₂). Anal. Calcd for C₄₄H₄₆O₈: C, 74.19; H, 6.60. Found: C, 74.09; H, 6.71.

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2′- O -(2,3,4,6-Tetra- O -benzyl-α-d -galacto-pyranosyl)glycerol ( 8)
¹H NMR (CDCl₃): δ = 7.40-7.10 (m, 25 H, arom. H), 4.95 (d, 1 H, J _1,2 = 3.6 Hz, H-1), 4.94-4.35 (m, 8 H, PhCH₂), 4.13-4.07 (m, 2 H, H-2, H-5), 3.98 (dd, 1 H, J _3,2 = 10.1 Hz, J _3,4 = 2.8 Hz, H-3), 3.87 (d, 1 H, H-4), 3.79-3.70 (m, 1 H, OCH), 3.60-3.50 (m, 5 H, 2 OCH₂, H-6a), 3.28 (dd, 1 H, J _6a,6b = 4.1 Hz, J _6b,5 = 9.6 Hz, H-6b). ¹³C NMR (CDCl₃): δ = 138.2-127.5 (arom. C), 99.4 (C-1), 85.4 (OCH), 79.4 (C-3), 76.4 (C-2), 74.6 (C-4), 74.5-73.6 (PhCH₂), 70.7 (C-5), 69.7 (C-6), 62.9 (OCH₂), 62.3 (OCH₂). Anal. Calcd for C₃₇H₄₂O₈: C, 72.99; H, 6.89. Found: C, 71.13; H, 7.42.

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General Procedure for the Catalytic Hydrogenation A mixture of compound 8 (300 mg, 0.488 mmol) and Pd/C 10% in EtOAc-MeOH-H₂O (4:4:2 mL) was stirred under a H₂ atmosphere at r.t. for 18 h. The mixture was filtered, concentrated, and co-evaporated with toluene. The compound was eluted from a column (3.0 × 30 cm) of Sephadex LH-20 with H₂O to give 1 (112 mg, 90%) as a white powder.


2′- O -(α-d -Galactopyranosyl)glycerol ( 1)
[α]_D +164 (c 1.0, H₂O), lit. 2: [α]_D +165. ¹H NMR (D₂O): δ = 5.13 (d, 1 H, J _1,2 = 3.9 Hz, H-1), 4.12-4.09 (m, 1 H, H-5), 3.95 (d, 1 H, J _4,3 = 2.8 Hz, H-4), 3.87 (dd, 1 H, J _3,2 = 10.1 Hz, H-3), 3.82-3.78 (m, 1 H, H-2), 3.75-3.70 (m, 7 H, 2 × OCH ₂, OCH, H-6a, H-6b). ¹³C NMR (CDCl₃): δ = 100.8 (C-1), 81.4 (OCH), 74.0 (C-5), 72.2 (C-3), 72.1 (C-4), 71.3 (C-2), 64.2 (OCH₂), 63.9 (OCH₂), 63.2 (C-6); cf. lit. 3. Anal. Calcd for C₉H₁₈O₈: C, 42.52; H, 7.14. Found: C, 42.36; H, 7.25.