1632 J ournal of Medicinal Chemistry, 1996, Vol. 39, No. 8
Leydet et al.
M); IR (CCl4, ν, cm-1) 3076 (dC-H), 2928-2855 (C-H, CH2-as
and -s), 1747-1720 (CdO, acid) 1622 (CdO, amide); 1H NMR
(250 MHz, DMSO-d6) δ 1.3 (m, 12H, CH2-3′-8′), 2.1 (m, 4H,
CH2-2′ and -9′), 3.4 (m, 6H, CH2-2-4), 4.2 (m, 1H, CH-1), 5.0
(m, 2H, CH2d-11′), 5.8 (m, 1H, CHd-10′); MS (FAB+, TG) m/z
282 [M + H]+, 116 [M + H - 166], 70 (iminium ion). Anal.
(C16H27NO3) C, H, N.
N-Un d ec-10′-en oyl-L-th r eon in e (4): method A; yield 49%;
mp 165-166 °C; Rf 0.66 (80/20 CHCl3/MeOH); [R]25D ) -14.4°
(MeOH, c ) 0.1 M); IR (KBr, ν, cm-1) 3405 (O-H), 3318 (N-H),
3090 (dC-H), 1711 (CdO, acid), 1628 (CdO, amide); 1H NMR
(250 MHz, CDCl3) δ 1.3 (m, 12H, CH2-3′-8′), 1.7 (t, 3H, CH3-
4), 2.1 (m, 2H, CH2-9′), 2.3 (t, 2H, CH2-2′, J ) 8 Hz), 4.4 (d,
1H, CH-2, J ) 8.4 Hz), 4.5 (m, 1H, CH-3), 5.0 (m, 2H, CH2d-
11′), 5.8 (m, 1H, CHd-10′), 6.8 (d, 1H, NH, J ) 8 Hz); MS
(FAB+, NBA) m/z 286 [M + H]+, 308 [M + Na]+, 571 [2M +
H]+, 268 [M + H - 18]+, 120 [M + H - 166(ketene)]+, 74
(iminium ion). Anal. (C15H27NO4) C, H, N.
(C-10′), 176.2 (C-1′), 180.9 (C-1); MS (FAB-, TG) m/z 296 [A]-,
318 [A + Na - H]-, 615 [2A + Na]-.
N-Un d ec-10′-en oyl-L-isoleu cin e (8): method B; yield 77%;
mp 100-101 °C; Rf 0.40 (90/10 CHCl3/MeOH); [R]25D ) +3.37°
(MeOH, c ) 0.1 M); IR (KBr, ν, cm-1) 3320 (N-H), 3070 (dC-
H), 2920-2849 (C-H, CH2-as and -s), 1720 (CdO, acid), 1648
(CdO, amide); 1H NMR (250 MHz, DMSO-d6) δ 0.9 (q, 6H,
2CH3-5), 1.4 (m, 12H, CH2-3′-8′), 1.5 (m, 2H, CH2-3), 1.6 (m,
1H, CH-4), 2.0 (m, 2H, CH2-9′), 2.1 (t, 2H, CH2-2′), 4.2 (m, 1H,
CH-2), 5.0 (m, 2H, CH2d-11′), 5.8 (m, 1H, CHd-10′), 8.0 (d,
1H, NH, J ) 7 Hz); MS (FAB+, NBA) m/z 298 [M + H]+, 132
[M + H - 166(ketene)], 86 (iminium ion). Anal. (C17H30NO3)
C, H, N.
Sod iu m Sa lt 8m : IR (KBr, ν, cm-1) 3340 (N-H), 3060 (dC-
H), 2922-2852 (C-H, CH2-as and -s), 1640 (CdO, amide); 13
C
NMR (50.32 MHz, D2O) δ 11.9 (CH3-5), 16.5 (CH3-6), 25.3 (C-
4), 26.8 (C-3′), 29.6-30 (C-4′-8′), 34.38 (C-9′), 36.9 (C-2′), 37.9
(C-3), 60.3 (C-2), 114.8 (C-11′), 139.4 (C-10′), 176.1 (C-1′), 179.3
(C-1); MS (FAB-, TG) m/z 296 [A]-, 318 [A + Na - H]-, 615
[2A + Na]-.
Sod iu m Sa lt 4m : IR (KBr, ν, cm-1) 3410 (O-H), 3070 (dC-
H), 2932-2856 (C-H, CH2-as and -s), 1640 (CdO, amide), 1596
(CO2-); 13C NMR (50.32 MHz, D2O) δ 20.1 (C-4), 29.46-29.97
(C-4′-C-8′), 34.32 (C-9′), 36.88 (C-2′), 60.33 (C-2), 68.50 (C-3),
114.9 (C-11′), 139.8 (C-10′), 176.8 (C-1), 177.4 (C-1′); MS (FAB-,
TG) m/z 284 [A]-, 306 [A + Na-H]-, 591 [2A + Na]-.
N-Un d ec-10′-en oyl-L-tyr osin e (9): method B; yield 46%;
mp 95-97 °C; Rf 0.27 (90/10 CHCl3/MeOH); [R]25 ) +20.75°
D
(MeOH, c ) 0.1 M); IR (KBr, ν, cm-1) 3420 (O-H), 3321 (N-H),
3080 (dC-H), 2927-2852 (C-H, CH2-as and -s), 1715 (CdO,
1
acid), 1642 (CdO, amide); H NMR (250 MHz, CD3OD) δ 1.4
N-Un d ec-10′-en oyl-L-p h en yla la n in e (5): method B; yield
(m, 12H, CH2-3′-8′), 2.1 (m, 2H, CH2-9′), 2.2 (t, 2H, CH2-2′, J
) 7.3 Hz), 3.0 (2q, 2H, CH2-3, AMX), 4.6 (m, 1H, CH-2), 5.0
(m, 2H, CH2d-11′), 5.1 (s, 1H, OH), 5.9 (m, 1H, CHd-10′), 6.7
(d, 2H, Ar-ortho), 7.1 (d, 2H, Ar-meta); MS (FAB+, GT) m/z
348 [M + H]+, 182 [M + H - 166(ketene)]+, 136 (iminium ion);
93 (phenonium ion). Anal. (C20H29NO4) C, H, N.
83%; mp 72-73 °C; Rf 0.46 (90/10 CHCl3/MeOH); [R]25
)
D
+13.8° (MeOH, c ) 0.1 M); IR (KBr, ν, cm-1) 3300 (N-H), 3072
(Ar-H), 3028 (dC-H), 2923-2851 (C-H, CH2-as and -s), 1721
(CdO, acid), 1644 (CdO, amide); 1H NMR (250 MHz, DMSO-
d6) δ 1.2 (m, 12H, CH2-3′-8′), 2.0 (m, 4H, CH2-2′ and -9′), 2.9
(m, 2H, CH2-3), 4.4 (m, 1H, CH-2), 5.0 (m, 2H, CH2d-10′), 5.8
(m, 1H, CHd-11′), 7.3 (s, 5H, Ar), 8.1 (d, 1H, NH, J ) 8 Hz),
10.5 (s, 1H, CO2H, exch); MS (FAB+, NBA) m/z 332 [M + H]+,
354 [M + Na]+, 166 [M + H - 166(ketene)]+, 120 (iminium
ion). Anal. (C20H29NO3) C, H, N.
Sod iu m Sa lt 9m : IR (KBr, ν, cm-1) 3408 (O-H), 3351 (N-
H), 3080 (Ar-H), 3032 (dC-H), 2924-2853 (C-H, CH2-as and
-s), 1590 (CO2-); 13C NMR (50.32 MHz, D2O) δ 26.35 (C-3′),
29.48-29.94 (C-4′-8′), 34.35 (C-9′) 36.87 (C-2′), 38.21 (C-3),
56.91 (C-2), 114.9 (C-11′), 116.3 (C-1′′ Ar), 129.3 (C-2′′ and -6′′
Ar), 131.1 (C-3′′ and -5′′ Ar), 139.8 (C-10′), 156.1 (C-4′′ Ar),
176.0 (C-1′), 179.1 (C-1); MS (FAB-, TG) m/z 346 [A]-, 368 [A
+ Na - H]-, 715 [2A + Na]-.
Sod iu m Sa lt 5m : IR (KBr, ν, cm-1) 3325 (N-H), 3072 (Ar-
H), 3030 (dC-H), 2927-2854 (C-H, CH2-as and -s), 1632 (CdO,
amide), 1598 (CO2-); 13C NMR (50.32 MHz, D2O) δ 26.57 (C-
3′), 29.3-30.2 (C-4′-C-8′), 34.55 (C-9′), 36.88 (C-2′), 38.51 (C-
3), 56.59 (C-2), 115.0 (C-11′), 126.9 (C-7 Ar), 128.9 (C-6-8 Ar),
129.9 (C-5-9 Ar), 138.9 (C-4 Ar), 139.5 (C-10′), 175.8 (C-1),
179.2 (C-1′); MS (FAB-, TG) m/z 330 [A]-, 352 [A - H + Na]-,
683 [2A + Na]-.
N-Un d ec-10′-en oyl-L-ser in e (10): method B; yield 87%; mp
68-69 °C; Rf 0.30 (90/10 CHCl3/MeOH); [R]25 ) +9.96°
D
(MeOH, c ) 0.1 M); IR (KBr, ν, cm-1) 3417 (O-H), 3315 (N-H),
3070 (dC-H), 2927-2854 (C-H, CH2-as and -s), 1714 (CdO,
1
acid), 1630 (CdO, amide); H NMR (90 MHz, CD3OD) δ 1.3
N-Un d ec-10′-en oyl-L-va lin e (6): method B; yield 84%; mp
92-93 °C; Rf 0.7 (90/10 CHCl3/MeOH); [R]25D ) -42.4° (MeOH,
c ) 0.1 M); IR (KBr, ν, cm-1) 3321 (N-H), 3070 (dC-H), 2921-
2850 (C-H, CH2-as and -s), 1725 (CdO, acid) 1648 (CdO,
amide); 1H NMR (250 MHz, CDCl3) δ 1.0 (d, 6H, 2CH3-4), 1.3
(m, 10H, CH2-4′-8′), 1.6 (m, 2H, CH2-3′), 2.0 (m, 2H, CH2-9′),
2.2 (m, 1H, CH-3), 2.3 (t, 2H, CH2-2′), 4.6 (q, 1H, CH-2), 5.0
(m, 2H, CH2d-11′), 5.8 (m, 1H, CHd-10′), 6.1 (d, NH, J ) 8
Hz), 10.7 (s, 1H, CO2H, exch); MS (FAB+, NBA) m/z 284 [M +
H]+, 266 [M + H - H2O]+, 238 [266 - CO]+, 72 (iminium ion).
Anal. (C16H28NO3) C, H, N.
Sod iu m Sa lt 6m : IR (KBr, ν, cm-1) 3350 (N-H), 3070 (dC-
H), 1650 (CdO, amide), 1597 (CO2-); 13C NMR (50.32 MHz,
D2O) δ 17.7 and 18.98 (2CH3-4), 25.77 (C-3′), 28.9-29.3 (C-
4′-8′), 31.08 (C-3), 33.79 (C-9′), 57.07 (C-2), 114.2 (C-11′), 139.1
(C-10′), 174.3 (C-1), 175.3 (C-1′); MS (FAB-, TG) m/z 282 [A]-,
304 [A + Na - H]-, 587 [2A + Na]-.
(m, 12H, CH2-3′-8′), 2.1 (m, 2H, CH2-9′), 2.3 (t, 2H, CH2-2′, J
) 8.4 Hz), 3.9 (m, 2H, CH2-3), 4.6 (t, 1H, CH-2), 4.9 (s, 1H,
OH), 5.1 (m, 2H, CH2d-11′), 6.0 (m, 1H, CHd-10′); MS (FAB+,
NBA) m/z 272 [M + H]+, 294 [M + Na]+ 543 [2M + H]+, 254
[M + H - H2O], 226 (254 - CO), 106 [M + H - 166(ketene)]+.
Anal. (C14H24NO4) C, H, N.
Sod iu m Sa lt 10m : IR (KBr, ν, cm-1) 3415 (O-H), 3348 (N-
H), 3072 (dC-H), 2919-2849 (C-H, CH2-as and -s), 1637 (CdO,
amide), 1598 (CO2-); 13C NMR (50.32 MHz, D2O) δ 26.28 (C-
3′), 29.45-29.93 (C-4′-8′), 34.32 (C-9′), 36.83 (C-2′), 57.69 (C-
2), 63.23 (C-3), 114.9 (C-11′), 140.0 (C-10′), 176.7 (C-1′), 177.3
(C-1); MS (FAB-, TG) m/z 270 [A]-, 292 [A + Na - H]-, 563
[2A + Na]-.
N-Un d ec-10′-en oyl-L-m eth ion in e (11): method B; yield
90%; mp 65-66 °C; Rf 0.24 (80/20 CHCl3/MeOH); [R]25
)
D
-7.62° (MeOH, c ) 0.1 M); IR (KBr, ν, cm-1) 3310 (N-H), 3073
(dC-H), 2924-2850 (C-H, CH2-as and -s), 1721 (CdO, acid),
1648 (CdO, amide); 1H NMR (90 MHz, CDCl3) δ 1.4 (m, 12H,
CH2-3′-8′), 1.6 (m, 2H, CH2-3), 2.1 (m, 2H, CH2-9′), 2.2 (s, 3H,
CH3-S), 2.3 (t, 2H, CH2-2′, J ) 8 Hz), 2.6 (t, 2H, CH2-4), 4.8
(m, 1H, CH-2), 5.1 (m, 2H, CH2d-11′), 6.0 (m, 1H, CHd-10′),
6.5 (d, 1H, NH, J ) 8 Hz); MS (FAB+, NBA) m/z 316 [M +
H]+, 338 [M + Na]+, 631 [2M + H]+, 268 [M + H - HSCH3]+,
N-Un d ec-10′-en oyl-L-leu cin e (7): method B; yield 64%; mp
99-101 °C; Rf 0.4 (90/10 CHCl3/MeOH); [R]25 ) +14.8°
D
(MeOH, c ) 0.1 M); IR (KBr, ν, cm-1) 3320 (N-H), 3070 (dC-
H), 2919-2848 (C-H, CH2-as and -s), 1724 (CdO, acid), 1648
(CdO, amide); 1H NMR (250 MHz, DMSO-d6) δ 0.9 (q, 6H,
2CH3-5), 1.4 (m, 12H, CH2-3′-8′), 1.5 (m, 2H, CH2-3), 1.6 (m,
1H, CH-4), 2.0 (m, 2H, CH2-9′), 2.1 (t, 2H, CH2-2′), 4.2 (m, 1H,
CH-2), 5.0 (m, 2H, CH2d-11′), 5.8 (m, 1H, CHd-10′), 8.0 (d,
NH, J ) 7 Hz); MS (FAB+, NBA) m/z 298 [M + H]+, 320 [M +
Na]+, 595 [2M + H]+, 252 [M + H - 46]+, 96 (iminium ion).
Anal. (C17H30NO3) C, H, N.
150 [M + H - 166(ketene)]+, 104 (iminium ion). Anal. (C16H29
NO2S) C, H, N.
-
N-Un d ec-10′-en oyl-L-h istid in e (13). To a suspension of
L-histidine methyl ester dihydrochloride (5 g, 20.7 mM) in 50
mL of dry CHCl3 were dropwise added at 0 °C TEA (5.8 mL)
and then undec-10-enoyl chloride (1) (2.2 mL, 10.3 mM). After
20 min under stirring at 0 °C to the mixture in the same
conditions were added new fractions of TEA (2.9 mL) and
chloride 1 (2.2 mL). Stirring was maintained for 30 min at 0
°C and then for 2 h at room temperature. The mixture was
Sod iu m Sa lt 7m : IR (KBr, ν, cm-1) 3330 (N-H), 3050 (dC-
H), 2932-2852 (C-H, CH2-as and -s), 1619 (CdO, amide), 1596
(CO2-); 13C NMR (50.32 MHz, D2O) δ 21.67 and 23.86 (2CH3-
5), 25.65 (C-3′), 26.71 (C-3), 29.6-30.16 (C-4′-8′), 34.38 (C-
9′), 36.93 (C-2′), 41.62 (C-4), 54.17 (C-2), 114.9 (C-11′), 139.5