One-pot Synthesis ofN-Formyl-O-acyl-threo- anderythro-DL-β-phenylserine Ethyl Esters and their Antiviral Properties

Abstract

A series of N-formyl-O-acyl-β-phenylserine derivatives 1b -7b were prepared by the interaction of N-acylβ-phenylserine ethyl esters 1a-7a with formic acid in presence of 1.5% HF. One-pot acyl group N→O migration followed N-formylation under elaborated reaction conditions. 1.96(CH 2 ,q, J = 8.0) 3.97 q, 0.73 t, 7.42 m J = 4.0, 5.0 J = 5.0 J = 4.0, 9.0 J = 9.0 0.98(CH 3 , t, J = 7.0) J = 7.0 J = 7.0 3a CDCl 3 7.20 s 5.09 d, b ) 4.71 dd, 6.29 d, 2.02(CH 2 , q, J = 6.5) 4.04 q, 0.91 t, J = 3.0 J = 3.0, 9.0 J = 8.0 1.11(CH 3 , t, J = 7.0) J = 7.0 J = 7.3 4a (CD 3 )CO 7.06 -5.20 d, 6.18 d, 4.67 dd, 7.69 d, 2.09(CH 2 , m) 3.97 q, 0.8 t, 7.42 m J = 3.0 J = 5.0 J = 3.0, 10.0 J = 10.0 3.58(CH 2 Br, m) J = 7.0 J8 4.37(CH, t, J = 8.0) J = 7.0 J = 7.0 7.09 -7.83 [(C 6 H 4 ) 2 C, m] 7a CDCl 3 7.11-5.04 dd, b ) 4.94 dd 6.11 d, 2.56(CH 2 , d, J = 7.0) 3.98 q, 1.04 t, 7.71 m J = 3.0, 7.0 J = 3.0, 7.0 J = 7.0 4.39(CH, t, J = 7.0) J = 7.0 J = 7.0 7.11 -7.71 [(C 6 H 4 ) 2 C, m] a ) Residues R are the same as in Scheme 1 b ) Overlapped with other signals Tab. 5 1 H NMR spectra (chemical shifts δ in ppm, multiplicity, coupling constants J in Hz) of compounds 1b-7b Comp. C 6 H 5 CH (OCO -R b ) -CH (NH-OCH)CO 2 CH 2 -CH 3 a ) 1b 7.18 s 6.00 d, 1.62 s 4.77 dd, 8.42 d, 8.2 s 3.91 q, 0.93 t, J = 5.0 J = 5.0, 9.0 J = 9.0 J = 7.0 J = 7.0 2b 7.20 s 6.25 d 1.64 s 5.11 dd, 7.63 d, 8.11 s 4.01 q, 0.91 t J = 5.0 J = 5.0, 9.0 J = 9.0 J = 7,0 J = 7.0 3b 7.16 -6.27 d, 2.02 (CH 2 , q, J = 7.0) 4.98 dd, c) 8.09 s 4.02 q, 0.87 t, 7.49 m J = 5.0 1.07(CH 3, t, J = 7.0) J = 5.0, 9.0 J = 7.0 J = 7.0 4b 7.14 -6.24 d, 2.73(CH 2 , t, J = 6.5) 5.02 dd, 7.68 d, 8.13 s 4.04 q, 0.90 t, 7.44 m J = 5.0 3.42(CH 2 Br, t, J = 6.5) J = 5.0, 8.0 J = 8.0 J = 7.0 J = 7.0 5b 6.98-6.27 d, 3.42(CH 2 , s) 4.99 dd, 7.51 d, 8.10 s 3.98 q, 0.91 t, 7.31 m J = 4.4 6.98 -7.31(C 6 H 5 , m) J = 4.4, 10.0 J = 10.0 J = 7.0 J = 7.0 6b 7.12 -6.23 d, 2.56(CH 2 , k, J = 8.0) 4.98 d, 7.60 d, 8,13 s 4.05 q, 0.95 t, 7.48 m J = 4.5 4.35(CH, t, J = 8.0) J = 4.5, 9.0 J = 9,0 J = 7.0 J = 7.0 7.12-7.,48[(C 6 H 4 ) 2 C, m] 7b 7.04 -6.21 d, 2.56(CH 2 , t, J = 8.0) 5.23 dd c) 8.15 s 4.09 q, 1.14 t, 7.73 m J = 7.0 4.33(CH, t, J = 8.0) J = 4.5, 9.0 J = 7.0 J = 7.0 7.04 -7.73[(C 6 H 4 ) 2 C, m] a ) The spectra were recorded in (CD 3 ) 2 CO except for 1b in DMSO-d 6 ; b ) The radicals R are the same as in Scheme 1 c ) Overlapped with other signals