Cyclic Trimers of Chiral Furan Amino Acids

Abstract

Chiral furan amino acids were synthesized as novel peptide building blocks. Cyclooligomerization of these monomers by a single-step process led to the selective formation of chiral C₃-symmetric cyclic trimers, which were studied for their structures and properties, like anion binding and antimicrobial activities.

Key words

chiral furan amino acids - anion binding - synthetic receptors - cyclic trimers - antimicrobial

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17

Selected physical data of 2b: R _f = 0.4 (silica, 8% MeOH in CHCl₃); [α]_D ²⁹ -33.9 (c 0.115, MeOH). ¹H NMR (200 MHz, DMSO-d ₆): δ = 8.37 (d, J = 9.52 Hz, 1 H, NH), 7.02 (d, J = 2.93 Hz, 1 H, furan ring proton), 6.51 (d, J = 2.97 Hz, 1 H, furan ring proton), 5.41 (dq, J = 9.52, 7.32 Hz, 1 H, C -H), 1.54 (d, J = 7.32 Hz, 3 H, Cβ-H ₃). MS (LSI-MS): m/z = 412 [M + H]⁺.
Selected physical data of 2c: R _f = 0.5 (silica, 8% MeOH in CHCl₃); [α]_D ²⁹ -36.4 (c 0.055, MeOH). ¹H NMR (200 MHz, DMSO-d ₆): δ = 8.17 (d, J = 10.41 Hz, 1 H, NH), 6.98 (d, J = 2.97 Hz, 1 H, furan ring proton), 6.49 (d, J = 2.97 Hz, 1 H, furan ring proton), 4.91 (dd, J = 10.41, 9.66 Hz, 1 H, Cα-H), 2.04 (m, 1 H, Cβ-H), 1.04 (d, J = 6.69 Hz, 3 H, Cγ-H ₃), 0.86 (d, J = 6.69 Hz, 3 H, Cγ-H′ ₃). MS (ESI): m/z = 496 [M + H]⁺, 518 [M + Na]⁺, 519 [M + Na + H]⁺.
Selected physical data of 2d: R _f = 0.5 (silica, 7% MeOH in CHCl₃); [α]_D ²⁹ -100.0 (c 0.070, MeCN). ¹H NMR (200 MHz, DMSO-d ₆): δ = 8.43 (d, J = 8.92 Hz, 1 H, NH), 7.17 (m, 5 H, aromatic protons), 6.83 (d, J = 2.97 Hz, 1 H, furan ring proton), 6.15 (d, J = 2.97 Hz, 1 H, furan ring proton), 5.46 (ddd, J = 8.92, 8.18 Hz, 1 H, Cα-H), 3.19 (m, 2 H, Cβ-H ₂). MS (LSI-MS): m/z = 640 [M + H]⁺, 662 [M + Na]⁺.

18

The details of the theoretical calculations will be published separately.

23

The association constant (K _a) was obtained by using the following equation: K _a = α/{(1 - α)([G] - α[H])}, where α = (δ - δ ₀)/(δ _max - δ ₀), δ ₀ is the initial chemical shift (host amide proton), δ is the chemical shift at each titration point, and δ _max is the chemical shift when the receptor is entirely bound (see ref. [21] ). The titrations were usually repeated several times to attain error limits as low as possible. The average association constant was determined from the values of each titration point and the standard deviations are specified.

25

The details of the biological studies will be published separately.