Asymmetric Synthesis and Structural Elucidation of C ₂-Symmetrical Optically Active Macrocycles Consisting of Two Biaryl and Two α-Amino Acid Moieties

Abstract

A series of chiral C ₂-symmetrical macrocycles containing two α-amino acids and two biaryl subunits have been designed and synthesized in moderate yields (36-53%). The absolute configurations of biaryl motifs in these chiral macrocycles were established by X-ray crystal structure analysis and CD measurements.

Key words

chiral macrocycle - biaryl - C ₂-symmetrical - absolute configuration - X-ray analysis

References and Notes

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General Procedure for the Syntheses of Chiral Macrocycles of 11a-c To a well-stirred solution of 10a-c in anhyd CH₂Cl₂ was added TFA. The resulting solution was stirred at r.t. for 2 h. The excess TFA was removed under the reduced pressure. The residue was dissolved in CH₂Cl₂ and washed with sat. aq NaHCO₃ three times. The organic layers were dried over anhyd Na₂SO₄. After filtration and concentration, the resulted residue was treated with 5% AcOH (aq) in CH₂Cl₂ at 40 ˚C overnight. The reaction mixture was diluted with CH₂Cl₂, and washed with H₂O three times. The organic layers were dried over anhyd Na₂SO₄. After filtration and concentration under reduced pressure, the resulted crude products were purified with flash column to afford macrocycles 11a-c in 36-53% yield.
Analytical Data of Chiral Macrocycle ( R , R , M , M )-11a [α]_D ^²³ -296.0 (c 1.0, CHCl₃). ^¹H NMR (400 MHz, CDCl₃):
δ = 7.63 (dd, J = 8.0, 1.2 Hz, 2 H), 7.53 (s, 2 H), 7.23-7.49 (m, 10 H), 7.12 (d, J = 7.6 Hz, 2 H), 7.07 (dd, J = 7.6, 1.2 Hz, 2 H), 3.64 (q, J = 6.8 Hz, 2 H), 3.38 (s, 6 H), 1.15 (d, J = 6.8 Hz, 6 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 172.6, 160.3, 142.2, 138.1, 138.0, 133.5, 132.9, 130.2, 129.7, 128.9, 128.7, 128.3, 128.1, 127.6, 63.1, 39.8, 21.8. ESI-HRMS:
m/z calcd for C₃₄H₃₃N₄O₂ [M + H⁺]: 529.2598; found: 529.2601 (-0.5 ppm, -0.3 mmu).

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The X-ray crystallographic data of compounds 11b and 11c were deposited to the Cambridge Crystallographic Data Centre, CCDC-773495 and CCDC-773496, respectively.