Bis-C-Glycosylation of Resorcinol Derivatives by an O→C-Glycoside Rearrangement

Abstracts

An efficient method for bis-C-glycosylation of resorcinol derivatives was developed by utilizing the O→C-glycoside rearrangement, where each of the two phenols serves as the pivot for selective and high-yield installation of two same or different sugar moieties.

Key words

bis-C-glycoside - C-glycosylation - rearrangement - resorcinol - scandium(III) triflate - pluramycin

References and Notes

• 1a Hacksell U. Daves GD. Prog. Med. Chem.  1985,  22:  1 
• 1b Suzuki K. Matsumoto T. In Recent Progress in the Chemical Synthesis of Antibiotics and Related Microbial Products   Vol. 2:  Lukacs G. Springer; Berlin: 1993.  p.353 
• 1c Postema MHD. C-Glycoside Synthesis   CRC: Florida: 1995. 
• 2a Séquin U. Prog. Chem. Org. Nat. Prod.  1986,  50:  58 
• 2b Pluramycin A. Kondo S. Miyamoto M. Naganawa H. Takeuchi T. Umezawa H. J. Antibiot.  1977,  30:  1143 
• 2c Séquin U. Ceroni M. Helv. Chim. Acta  1978,  61:  2241 
• 2d Kidamycin: Furukawa M. Hayakawa I. Ohta G. Iitaka Y. Tetrahedron  1975,  31:  2989 
• 3 Hansen MR. Hurley LH. Acc. Chem. Res.  1996,  29:  249 
• 4a Parker KA. Koh Y.-H. J. Am. Chem. Soc.  1994,  116:  11149 
• 4b Kaelin DE. Lopez OD. Martin SF. J. Am. Chem. Soc.  2001,  123:  6937 
• 4c Martin SF. Pure Appl. Chem.  2003,  5:  63 
• 5a Matsumoto T. Katsuki M. Suzuki K. Tetrahedron Lett.  1988,  29:  6935 
• 5b See also: Kometani T. Kondo H. Fujimori Y. Synthesis  1988,  1005 
• 5c Matsumoto T. Yamaguchi H. Tanabe M. Yasui Y. Suzuki K. Tetrahedron Lett.  2000,  41:  8393 
• 5d Hosoya T. Takashiro E. Matsumoto T. Suzuki K. J. Am. Chem. Soc.  1994,  116:  1004 
• 6a Ben A. Yamauchi T. Matsumoto T. Suzuki K. Synlett  2004,  225 
• 6b For a review on the use of Sc(OTf)₃ in organic synthesis, see: Kobayashi S. Eur. J. Org. Chem.  1999,  15 

7

Procedure for the Preparation of Mono- C -Glycoside 7.
To a stirred mixture of Sc(OTf)₃ (67.0 mg, 0.136 mmol), mono-protected resorcinol derivative 6 (1.00 g, 2.76 mmol), powdered Drierite^® (1.4 g) in 1,2-dichloroethane (27 mL), was added fucosyl acetate 5 (659 mg, 1.38 mmol) in 1,2-dichloroethane (8 mL) at -30 °C. After the temperature was gradually raised to 0 °C during 4.5 h, the mixture was poured into sat. aq NaHCO₃ solution. After filtration through a Celite^® pad, the products were extracted with EtOAc (3×), and the combined organic extracts were washed with brine, and dried over Na₂SO₄. Removal of the solvents in vacuo and purification by silica gel chromatography (hexane-acetone-CH₂Cl₂ = 20:1:1) afforded C-glycoside 7 (1.02 g, 95%); mp 120-121 °C (hexane-EtOAc).

8

The reaction of compound 8a and fucosyl acetate 5 (2 equiv) under the Sc(OTf)₃-promoted conditions [25 mol% of Sc(OTf)₃, Drierite^®, 1,2-dichloroethane, -30 °C to T °C] is shown below. The outcome was not satisfactory, but was better than those from other attempted conditions. When the reaction was stopped at 0 °C, the desired bis-C-glycoside 28 was obtained in 48% yield along with the O-glycoside 27 (29%). This shows that the protection of one of the phenolic hydroxyls remarkably retards both of the O-glycosylation and the migration of the sugar [note: the reaction of 8e and 5 went to completion at 0 °C]. Further warming of the reaction accelerated the O-glycosidation and the migration of the sugar, but also caused undesired reactions to give many side products including 29 as the main constituent, which was most probably formed by the hydride shift from the C(5) of the sugar to the C(1) (see A). The yield of 28 did not exceed 68%. Prolongation of the reaction time around 0 °C did not give better result (Scheme [4] ).

Scheme 4

9

Molecular sieves (5A) are also usable but the reactions thereof required somewhat higher temperature and longer reaction period.

10

Bis-C-glycoside 9: mp 131-132 °C; [α]_D ³⁰ -18.0 (c 1.02, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 1.26 (d, 6 H, J = 6.0 Hz, H-6), 2.17 (s, 3 H, ArCH ₃ ), 3.60-3.61 (m, 4 H, H-2,5), 3.71 (d, 2 H, J = 1.6 Hz, H-4), 3.84 (d, 2 H, J = 10.2 Hz, benzylic), 4.14-4.15 (m, 4 H, H-1,3), 4.46 (d, 2 H, J = 10.2 Hz, benzylic), 4.76 (d, 2 H, J = 12.0 Hz, benzylic), 4.77 (d, 2 H, J = 12.2 Hz, benzylic), 4.82 (d, 2 H, J = 12.0 Hz, benzylic), 5.11 (d, 2 H, J = 12.2 Hz, benzylic), 6.71 (s, 1 H, ArH), 7.04-7.41 (m, 30 H, PhCH₂), 7.95 (s, 2 H, ArOH). ¹³C NMR (75 MHz, CDCl₃): δ = 8.2, 17.5, 72.7, 74.4, 74.6, 75.3, 76.6, 78.5, 82.3, 83.9, 113.6, 114.3, 127.3, 127.4, 127.48, 127.53, 127.90, 127.95, 128.2, 128.4, 128.7, 137.9, 138.56, 138.64, 154.9. Anal. Calcd for C₆₁H₆₄O₁₀: C, 76.54; H, 6.74. Found: C, 76.24; H, 6.81. ORTEP drawing of 9 is shown below (Figure [3] ).

Figure 3

11

TBDPS ether, when employed as the protecting group of a phenolic hydroxyl of methyl 2,6-dihydroxybenzoate, did not survive in the reaction. Thus, we opted for the allyl ether instead.