Stereoselection of 3,4-cis and 3,4-trans Catechin and Catechin Condensation under Intramolecular Coupling Method [1]

Abstract

A high level of stereoselection between 3,4-cis and 3,4-trans catechin-catechin condensation under intramolecular coupling method has been realized by changing the diester linker between the nucleophile and the electrophile. The azelaic acid ­linker gave exclusively 3,4-trans catechin-catechin dimer, whereas glutaric acid linker gave 3,4-cis catechin-catechin dimer as the sole product.

polyphenol - oligomeric flavonoid - catechin dimmer - B-type procyanidin - diester linker

References

1

This report is Part 7 in the series ‘Synthetic studies of proanthocyanidins’. For part 6 see ref. [7]

2 Harborne JB. The Flavonoids: Advances in research from 1986   Chapman and Hall; London: 1993. 

3 Harborne FRSJB. Baxter H. The Handbook of Natural Flavonoids   John Wiley and Sons; New York: 1999. 

4 There are many reports describing the biological activities of proanthocyanidins. A recent noteworthy report is: Kozikowski AP. Tuckmantel W. Böttcher G. Romanczyk LJ. J. Org. Chem.  2003,  68:  1641 

5 Saito A. Nakajima N. Tanaka A. Ubukata M. Tetrahedron  2002,  58:  7829 

6 Saito A. Nakajima N. Matsuura N. Tanaka A. Ubukata M. Heterocycles  2004,  62:  479 

7 Saito A. Tanaka A. Ubukata M. Nakajima N. Synlett  2004,  1069 

8 Saito A. Nakajima N. Tanaka A. Ubukata M. Tetrahedron Lett.  2003,  44:  5449 

9 Saito A. Nakajima N. Tanaka A. Ubukata M. Heterocycles  2003,  61:  287 

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12

Data for 23: To a solution of (2R,3S,4S)-5,7,3′,4′-tetra-benzyloxy-4-ethoxyethyloxy-flavan-3-yl (2R,3S)-5,7,3′,4′-tetrabenzyloxy-flavan-3-yl azelate (44 mg, 0.028 mmol) in CH₂Cl₂ (20 mL) was added dropwise TMSOTf (0.056 mL, 0.028 mmol, 0.5 M solution in CH₂Cl₂) at -20 °C. After stirring for 5 min, the pale yellow reaction mixture was quenched with sat. NaHCO₃. The aq solution was extracted with CHCl₃ and the combined organic phase were washed with H₂O and brine, and dried (Na₂SO₄). Filtration, concentration and preparative silica gel TLC purification (hexane-EtOAc, 2:1) afforded 17 mg (0.012 mmol, 42%) of cyclic compound 23 as a single product. [α]_D ²⁵ -93.1 (c 0.34, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 7.40-7.18 (35 H, m), 7.06-6.93 (5 H, m), 6.84-6.76 (3 H, m), 6.56 (1 H, d, J = 2.2 Hz), 6.37 (1 H, d, J = 8.3 Hz), 6.10 (1 H, d, J = 2.1 Hz), 6.01 (1 H, dd, J = 9.6, 10.0 Hz), 6.00 (1 H, d, J = 2.1 Hz), 5.89 (1 H, s), 5.87 (1 H, dd, J = 2.2, 8.3 Hz), 5.36 (1 H, br s), 5.25-5.22 (1 H, m), 5.08-4.81 (8 H, m), 5.05 (1 H, d, J = 9.6 Hz), 4.86 (1 H, d, J = 11.9 Hz), 4.77 (1 H, d, J = 11.9 Hz), 4.75 (1 H, d, J = 11.4 Hz), 4.73 (1 H, d, J = 12.0 Hz), 4.68 (1 H, d, J = 10.0 Hz), 4.64 (1 H, d, J = 11.4 Hz), 4.61 (1 H, d, J = 11.7 Hz), 4.56 (1 H, d, J = 12.0 Hz), 4.46 (1 H, d, J = 11.7 Hz), 2.99-2.93 (1 H, m), 2.32-2.22 (1 H, m), 2.03 (1 H, dd, J = 2.4, 16.6 Hz), 1.97-1.90 (1 H, m), 1.84-1.74 (2 H, m), 1.25-0.80 (10 H, m). ¹³C NMR (100 MHz, CDCl₃):
δ = 174.3, 171.4, 158.4, 157.5, 157.4, 155.7, 151.7, 148.9, 148.6, 148.51, 148.48, 138.0, 137.5, 137.31, 137.25, 137.21, 137.17, 136.9, 132.1, 130.8, 128.5-126.9 (C × 27), 121.0, 118.9, 117.1, 114.8, 114.6, 114.4, 112.0, 109.8, 108.2, 100.9, 94.8, 94.5, 90.4, 80.7, 71.6, 71.4, 71.11, 71.05, 70.2, 70.1, 70.0, 69.9, 69.0, 35.4, 34.4, 32.9, 29.7, 26.3, 24.9, 24.0, 23.0, 19.0. IR (neat): 3065 (w), 3032 (w), 2930 (m), 2862 (w), 2361 (w), 1732 (s), 1606 (s), 1512 (s), 1454 (s), 1379 (m), 1263 (m), 1213 (m), 1124 (s), 1026 (m), 910 (w), 851 (w), 812 (w), 737 (s), 696 (s) cm^-1. FAB-MS: m/z = 1450.6 (81), 1451.6 (100) [M + H]⁺, 1452.6 (79), 1453.6 (43). FAB-HRMS: m/z calcd for C₉₅H₈₇O₁₄ [M + H]⁺: 1451.6096. Found: 1451.6136.