720 H. Pan et al.
1H), 2.881-2.862 (m, 1H), 2.769-2.723 (m, 1H), 2.312 (m,
1H), 0.871-0.856 (m, 3H), 0.839-0.822 (d, 3H); ESI-MS
m/z: [M+H]+ 368.2.
General procedure for the synthesis of L-isoserine-L-
phenylglycine-L-leucyl (16k)
A white solid, yield: 49.8%, mp. 205–206°C, 1H NMR
(DMSO-d6) δ12.549 (s, J=7.8 Hz, 1H), 8.391 (d, J=7.8 Hz, 1H),
8.298 (s, 2H), 8.313 (d, J=7.8 Hz, 1H), 7.278-7.250 (m, 5H),
6.511 (s, 1H), 4.471-4.442 (m, 1H), 4.213-3.932 (m, 1H), 4.221-
3.997 (m, 1H), 3.242 (dd, J=13.8 Hz, J=8.4 Hz, 1H), 3.012(dd,
J=13.8 Hz, J=8.4 Hz, 1H), 1.522-1.442 (m, 3H), 0.881-0.876
(m, 3H), 0.852-0.841(d, 3H); ESI-MS m/z: [M+H]+ 352.4.
General procedure for the synthesis of L-isoserine-L-
valine-L-valine (16f)
A white solid, yield: 55.0%, mp. 181–182°C, 1H NMR
(DMSO-d6) δ12.600 (s, J = 7.8 Hz, 1H), 8.391 (d, J = 7.8
Hz, 1H), 8.331 (s, 2H), 8.298 (d, J = 7.8 Hz, 1H), 6.499 (s,
1H), 4.471 -4.443 (m, 1H), 4.211-3.732 (m, 1H), 4.119-
3.987 (m, 1H), 3.239 (dd, J = 13.8 Hz, J = 8.4 Hz, 1H),
3.011 (dd, J = 13.8 Hz, J = 8.4 Hz, 1H), 2.286 (m, 1H),
2.262 (m, 1H), 0.885-0.867 (m, 3H), 0.880-0.846 (m,
3H), 0.862-0.821(d, 3H), 0.858-0.842(d, 3H); ESI-MS
m/z: [M+H]+ 304.4.
General procedure for the synthesis of L-isoserine-L-
tyrosinase-L-leucyl (16l)
A pink solid, yield: 40.6%, mp. 104–106°C, 1H NMR
(DMSO-d6) δ 12.599 (s, J= 7.8 Hz, 1H), 8.289 (d, J= 7.8 Hz,
1H), 8.223 (s, 2H), 8.011 (s, 1H), 7.759 (d, J= 7.8 Hz, 1H),
6.951 (s, 2H), 6.682(s, 2H), 6.495 (s, 1H), 4.455-4.439 (m,
1H), 4.229 -3.804 (m, 1H), 4.151-3.989 (m, 1H), 3.191 (dd,
J= 13.8 Hz, J= 8.4 Hz, 1H), 2.981 (dd, J= 13.8 Hz, J= 8.4
Hz, 1H), 2.981-2.872 (m, 1H), 2.779-2.743 (m, 1H), 1.502-
1.446 (m, 3H), 0.869-0.8660 (m, 3H), 0.840-0.812 (d, 3H);
ESI-MS m/z: [M+H]+ 382.5.
General procedure for the synthesis of L-isoserine-L-
phenylglycine-L-phenylalanine (16g)
A white solid, yield: 48.1%, mp. 196–198°C, 1H NMR
(DMSO-d6) δ 12.598 (s, J= 7.8 Hz, 1H), 8.267 (d, J= 7.8 Hz,
1H), 8.219 (s, 2H), 7.743 (d, J= 7.8 Hz, 1H), 7.310 -7.275
(m, 5H), 7.026-7.014 (m, 5H), 6.520 (s, 1H), 4.449-4.429
(m, 1H), 4.219-3.939 (m, 1H), 4.111 -3.893 (m, 1H), 3.099
(dd, J= 13.8 Hz, J= 8.4 Hz, 1H), 2.902 (dd, J= 13.8 Hz,
J= 8.4 Hz, 1H), 2.869-2.849 (m, 1H), 2.768-2.688 (m, 1H);
ESI-MS m/z: [M+H]+ 386.2.
General procedure for the synthesis of L-isoserine-L-
eucyl-L-tyrosinase (16m)
A pink solid, yield: 42.6%, mp. 129–131°C, 1H NMR
(DMSO-d6) δ 12.612 (s, J= 7.8 Hz, 1H), 8.314 (d, J= 7.8
Hz, 1H), 8.123 (s, 2H), 8.023 (s, 1H), 7.859 (d, J= 7.8 Hz,
1H), 7.002 (s, 2H), 6.692(s, 2H), 6.512 (s, 1H), 4.465-4.449
(m, 1H), 4.234 -3.814 (m, 1H), 4.161-3.978 (m, 1H), 3.291
(dd, J= 13.8 Hz, J= 8.4 Hz, 1H), 3.002(dd, J= 13.8 Hz, J= 8.4
Hz, 1H), 2.981-2.792 (m, 1H), 2.783-2.763 (m, 1H), 1.522-
1.486 (m, 3H), 0.872-0.856 (m, 3H), 0.845-0.822 (d, 3H);
ESI-MS m/z: [M+H]+ 382.5.
General procedure for the synthesis of L-isoserine-L-
valine- L-leucyl (16h)
A white solid, yield: 55.0%, mp. 182–183°C, 1H NMR
(DMSO-d6) δ 12.588 (s, J=7.8 Hz, 1H), 8.389 (d, J=7.8 Hz,
1H), 8.312 (s, 2H), 8.310 (d, J=7.8 Hz, 1H), 6.510 (s, 1H),
4.469 -4.439 (m, 1H), 4.199 -3.832 (m, 1H), 4.219-4.001 (m,
1H), 3.301 (dd, J=13.8 Hz, J=8.4 Hz, 1H), 3.021 (dd, J=13.8
Hz, J=8.4 Hz, 1H), 2.290 (m, 1H), 2.259 (m, 1H), 1.499 -1.435
(m, 3H), 0.895-0.877 (m, 3H), 0.889-0.856 (m, 3H), 0.872-
0.831(d, 3H), 0.862-0.851 (d, 3H); ESI-MS m/z: [M+H]+ 318.4.
General procedure for the synthesis of L-isoserine-L-
phenylalanine-L-phenylalanine (16n)
A white solid, yield: 45.1%, mp. 184–185°C, 1H NMR
(DMSO-d6) δ12.588 (s, J=7.8 Hz, 1H), 8.277 (d, J=7.8 Hz,
1H), 8.223 (s, 2H), 7.750 (d, J=7.8 Hz, 1H), 7.311 -7.285 (m,
5H), 7.036-7.024 (m, 5H), 6.519 (s, 1H), 4.454-4.432 (m,
1H), 4.221-3.949 (m, 1H), 4.121 -3.993 (m, 1H), 3.199 (dd,
J=13.8 Hz, J=8.4 Hz, 1H), 2.913 (dd, J=13.8 Hz, J=8.4 Hz,
1H), 2.879-2.855 (m, 1H), 2.778-2.698 (m, 1H), 2.832-1.794
(m, 1H), 2.509-2.434 (m, 2H); ESI-MS m/z: [M+H]+ 410.2.
General procedure for the synthesis of L-isoserine-L-
leucyl -L-valine (16i)
A white solid, yield: 53.0%, mp. 181–182°C, 1H NMR
(DMSO-d6) δ 12.579 (s, J=7.8 Hz, 1H), 8.401 (d, J=7.8 Hz,
1H), 8.308 (s, 2H), 8.309 (d, J=7.8 Hz, 1H), 6.499 (s, 1H), 4.471
-4.439 (m, 1H), 4.211 -3.932 (m, 1H), 4.221-4.101 (m, 1H),
3.321 (dd, J=13.8 Hz, J=8.4 Hz, 1H), 3.121 (dd, J=13.8 Hz,
J=8.4 Hz, 1H), 2.311 (m, 1H), 2.246 (m, 1H), 1.502 -1.445 (m,
3H), 0.898-0.887 (m, 3H), 0.891-0.876 (m, 3H), 0.868-0.842
(d, 3H), 0.871-0.841 (d, 3H); ESI-MS m/z: [M+H]+ 318.4.
General procedure for the synthesis of 15a–15c
Compound 15a was synthesized firstly through the
condensation reaction of N-protected L-isoserine(11)
and L-phenylalanyl-4-methoxybenzylamine following
the general procedure as described above (preparation
of 6a), and then deprotecting the Boc group in the satu-
rated HCl/EtOAc solution as the preparation of 8a, yield:
General procedure for the synthesis of L-isoserine-L-
chloramphenicol-L-leucyl (16j)
Awhitesolid, yield:53.0%, mp. 180°C, 1HNMR(DMSO-d6)
δ 12.579 (s, J= 7.8 Hz, 1H), 8.168-8.153 (d, J= 7.8 Hz, 2H),
7.868-7.671 (d, 2H), 5.254-5.249 (s, 1H), 4.485-4.480 (s,
1H), 4.053 -4.036 (m, 1H), 3.978-3.960 (m, 1H), 2.908-
2.881 (m, 1H), 2.760-2.501 (m, 1H), 1.507-1.496 (d, 2H),
1.429-1.400 (m, 1H), 0.823-0.797 (m, 6H); ESI-MS m/z:
[M+H]+ 442.2.
1
76.1%. mp. 180–182°C, H NMR (DMSO-d6) δ 8.597 (d,
J= 7.8 Hz, 1H), 7.929-7.917 (s, 2H), 7.907 (d, J= 7.8 Hz, 1H),
7.246-7.111 (m, 5H), 6.875-6.863 (s, 2H), 6.520 (s, 1H),
6.483-6.476 (s, 2H), 4.462 (m, 2H), 4.468-4.461 (m, 1H),
4.013-3.939 (m, 1H), 4.245-4.170 (m, 2H), 3.733 (s, 3H),
3.047 (dd, J= 13.8 Hz, J= 8.4 Hz, 1H), 2.984 (dd, J= 13.8 Hz,
Journal of Enzyme Inhibition and Medicinal Chemistry