Synthesis of Isocyano Peptides by Dehydration of the N-Formyl Derivatives

Abstract

Phosphoryl chloride in combination with triethylamine dehydrates N-formyl peptides to provide the corresponding iso­cyano peptides in excellent yields.

Key words

dehydration - N-formyl - isocyanide - isocyano peptide - phosphoryl chloride

References

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15

Compound 4: R_f = 0.43 (EtOAc/heptane = 1/1); [α]_D = +13.8 (c 0.3, CHCl₃). IR (CHCl₃): ν = 3422, 2138, 1744, 1684, 1603, 1522, 1497, 1437, 1363, 1180 cm^-1.
¹H NMR (250 MHz, CDCl₃, ppm): δ = 3.08-3.30 (m, 4 H), 3.69 (s, 3 H,), 4.37 (dd, J = 4.5 Hz, 7.3 Hz, 1 H), 4.84 (dt, J = 5.7 Hz, 7.8 Hz, 1 H), 6.73 (d, J = 5.7 Hz, 1 H), 7.20-7.33 (m, 10 H). ¹³C NMR (62.5 MHz, CDCl₃, ppm): δ = 37.6, 38.3, 52.4, 53.1, 59.4, 127.3, 127.6, 127.7, 129.6, 129.0, 134.4, 134.8, 164.1, 170.7. MS (EI): m/z = 336 (M⁺), 227, 245. Anal. Calcd for C₂₀H₂₀N₂O₃: C, 71.43; H, 5.95; N, 8.33. Found: C, 71.44; H, 5.98; N, 8.30. Compound 6: R_f = 0.48 (EtOAc/heptane = 1/1.5); [α]_D = +17.5 (c 0.5, CHCl₃). IR (CHCl₃): ν = 3421, 3012, 2138, 1745, 1685, 1603, 1521, 1497, 1455, 1362, 1210, 1280, 1120 cm^-1. ¹H NMR (250 MHz, CDCl₃, ppm): δ = 3.00-3.30 (m, 4 H), 3.72 (s, 3 H), 4.35 (dd, J = 4.2 Hz, 7.8 Hz, 1 H), 4.84 (dd, J = 6.7 Hz, 12.7 Hz, 1 H), 6.72 (d, J = 6.7 Hz, 1 H), 7.15-7.32 (m, 10 H). ¹³C NMR (62.5 MHz, CDCl₃, ppm): δ = 37.8, 38.9, 52.6, 53.6, 59.9, 127.5, 127.8, 128.8, 129.2, 129.5, 134.7, 135.2, 164.7, 170.9. MS (EI): m/z = 336 (M⁺), 277, 245. Anal. Calcd for C₂₀H₂₀N₂O₃: C, 71.43; H, 5.95; N, 8.33. Found: C, 69.92; H, 6.05; N, 8.15.