Facile Syntheses of (2R,3R)-(−)- and (2S,3S)-(+)-Chicoric Acids

Abstract

Practical and efficient syntheses of (2R, 3R)-(−)- and (2S, 3S)-(+)-chicoric acids are reported, which may be amenable to analogue preparation.

Notes

Compound 5 has been previously prepared (for example: Haslam E. Makinson G. K. Naumann M. O. Cunningham J. J. Chem. Soc. 1964 2137.) It is easily synthesized on large scale by treatment of 3,4-dihydroxycinnamic acid with acetic anhydride (10 equivalents) in pyridine (v/v = 5:1) in the dark overnight at room temperature. Upon removal of solvent, residue is crystallized from EtOAc:hexane to provide diacetyl caffeic acid as a white solid. Reflux (3 h) with thionyl chloride (5 equivalents) in benzene (v/v = 8:1) provides 5 upon removal of solvent.

Mp 153–155 °C; [α]²⁵ _D −14° (CHCl₃, c 0.51); ¹H NMR (250 MHz, CDCl₃) δ 7.73 (d, J = 16.0 Hz, 2H), 7.44–7.36 (m, 4H), 7.24 (d, J = 8.3 Hz, 2H), 6.50 (d, J = 16.0 Hz, 2H), 5.79 (s, 2H), 2.30 (s, 6H), 2.28 (s, 6H), 1.41 (s, 18 H); FABMS m/z 756 (MH)⁺. Anal. calcd. for C₃₈H₄₂O₁₆: C, 60.47; H, 5.61. Found: C, 60.38; H, 5.65.

Mp 186–188 °C; [α]²⁵ _D −159° (MeOH, c 0.16); ¹H NMR (250 MHz, DMSO-d₆) δ 7.81 (d, J = 1.8 Hz, 2H), 7.76–7.70 (m, 4H), 7.34 (d, J = 8.4 Hz, 2H), 6.78 (d, J = 16.2 Hz, 2H), 5.74 (s, 2H), 2.28 (s, 12H); FABMS m/z 644 (MH)⁺. Anal. calcd. for C₃₀H₂₆O₁₆: C, 56.08; H, 4.08. Found: C, 55.82; H, 4.17.

8. Mp 204–206 °C; [α]²⁵ _D −333° (MeOH, c 0.10; lit.¹ −384.2° (MeOH, c 1.075)); ¹H NMR (250 MHz, DMSO-d₆) δ 9.69 (s, 2H), 9.16 (s, 2H), 7.55 (d, J = 15.8 Hz, 2H), 7.09–7.07 (m, 4H), 6.77 (d, J = 8.6 Hz, 2H), 6.36 (d, J = 15.9 Hz, 2H), 5.67 (s, 2H); FABMS m/z 475 (MH)⁺. Anal. calcd. for C₂₂H₁₈O₁₂·⁷/₄H₂O: C, 52.23; H, 4.28. Found: C, 52.07; H, 4.33.

[α]²⁵ _D +340° (MeOH, c 0.14). Other physical data were identical to that displayed by 2.