C. W. Phoon et al. / Tetrahedron 60 (2004) 11619–11628
11627
TFA–CH2Cl2 (1:1, 2 mL) at rt for 18 h. Following that, the
cleavage suspension was filtered and the resin was washed
with CH2Cl2 (3!5 mL). The filtrate and collected washings
were concentrated under reduced pressure to afford the
product. This procedure was employed for the syntheses of
compounds 15a–d, f, h–m. Sasrine resin-bound Fmoc-L-
Ser(t-Bu) was used for the preparation of compound 15m.
2.1 Hz), 7.35–7.40 (3H, m), 7.49 (1H, d, JZ15.8 Hz), 7.54
(2H, br dd, JZ7.6, 1.6 Hz); 13C NMR (100 MHz, CD3OD)
d 37.8, 55.7, 116.2, 121.4, 128.9, 129.1, 129.9, 130.9, 131.3,
136.2, 142.2, 157.3, 168.3, 175.0; (C)-HR-ESIMS m/z
312.1236 [MCH]C (calcd for C18H18NO4, 312.1236).
3.7.4. N-(4-Pentenoyl)-L-tyrosine (15d). Yield: 11.7 mg
(98%). Pale yellow oil. nmax (thin film) 3600–3100, 1727,
1
3.7. Synthetic procedure of compounds 15 using PyBOP
coupling
1645 cmK1; H NMR (400 MHz, acetone-d6) d 2.25–2.27
(4H, m), 2.89 (1H, dd, JZ13.9, 8.2 Hz), 3.08 (1H, dd, JZ
13.9, 5.1 Hz), 4.65 (1H, m), 4.89 (1H, dd, JZ9.8, 1.6 Hz),
4.98 (1H, br d, JZ17.1 Hz), 5.76 (1H, m), 6.74 (2H, d, JZ
8.4 Hz), 7.07 (2H, d, JZ8.4 Hz); 13C NMR (100 MHz,
CD3OD) d 30.8, 36.1, 37.7, 55.3, 115.7, 116.1, 129.2, 131.3,
138.2, 157.3, 175.2; (C)-HR-ESIMS m/z 264.1231
[MCH]C (calcd for C14H18NO4, 264.1236).
To the Wang resin-bound Fmoc-amino acid (0.45–
0.63 mmol/g; 100 mg, 0.045–0.063 mmol) contained in a
fritted polyethylene filtration tube was added 20%
piperidine/DMF (2 mL). The resin suspension was stirred
gently at rt for 20 min, then filtered. The Fmoc deprotection
was carried out again. The resin was then washed with
CH2Cl2 (3!5 mL), followed by drying under vacuum. To
the dried resin was added acid (0.23–0.32 mmol), PyBOP
(0.23–0.32 mmol) and HOBt (0.23–0.32 mmol). This
mixture was suspended in anhydrous DMA (2 mL), and
distilled diisopropylethylamine (0.45–0.63 mmol) was
added. The suspension was stirred gently at rt for 18 h,
then filtered. The resin was washed successively with DMF
(3!5 mL), THF–H2O 3:2 (3!5 mL), THF (3!5 mL),
CH2Cl2 (3!5 mL), then dried under vacuum. The deriva-
tised resin was transferred into a round bottom flask, and
treated with TFA–CH2Cl2 (1:1, 2 mL) at rt for 18 h.
Following that, the cleavage suspension was filtered and
the resin was washed with CH2Cl2 (3!5 mL). The filtrate
and collected washings were concentrated under reduced
pressure to afford the product. This procedure was employed
for the syntheses of compounds 15e and 15g.
3.7.5. N-(transK2-Pentenoyl)-L-tyrosine (15e). Yield:
11.5 mg (98%). Pale yellow oil. nmax (thin film) 3600–
1
3100, 1724, 1667 cmK1; H NMR (400 MHz, CD3OD) d
1.05 (3H, t, JZ7.5 Hz), 2.20 (2H, qdd, JZ7.5, 6.5, 1.7 Hz),
2.89 (1H, dd, JZ14.0, 8.8 Hz), 3.11 (1H, dd, JZ14.0,
5.2 Hz), 4.65 (1H, dd, JZ8.8, 5.2 Hz), 5.95 (1H, dt, JZ15.4,
1.7 Hz), 6.69 (2H, dt, JZ8.6, 2.0 Hz), 6.79 (1H, dt, JZ15.4,
6.5 Hz), 7.03 (2H, dt, JZ8.6, 2.0 Hz); 13C NMR (100 MHz,
CD3OD) d 12.8, 26.1, 37.7, 55.5, 116.2, 123.3, 129.1, 131.2,
147.7, 157.3, 168.5, 175.0; (C)-HR-ESIMS m/z 264.1236
[MCH]C (calcd for C14H18NO4, 264.1236).
3.7.6. N-Dodecanoyl-L-tyrosine (15f). Yield: 15.2 mg
(99%). Pale yellow solid, mp 122–125 8C. nmax (Nujol)
1
3600–3100, 3302, 1706, 1643 cmK1; H NMR (400 MHz,
CD3OD) d 0.90 (3H, t, JZ7.1 Hz), 1.20–1.37 (16H, m),
1.50 (2H, tt, JZ7.4, 7.4 Hz), 2.15 (2H, t, JZ7.4 Hz), 2.83
(1H, dd, JZ14.0, 9.4 Hz), 3.11 (1H, dd, JZ14.0, 4.9 Hz),
4.60 (1H, dd, JZ9.4, 4.9 Hz), 6.69 (2H, dt, JZ8.5, 2.0 Hz),
7.03 (2H, dt, JZ8.5, 2.0 Hz); 13C NMR (100 MHz,
CD3OD) d 14.4, 23.7, 26.9, 30.1, 30.5, 30.6, 30.7, 33.1,
36.8, 37.7, 55.2, 116.2, 129.1, 131.2, 157.3, 175.1, 176.2;
(C)-HR-ESIMS m/z 364.2485 [MCH]C (calcd for
C21H34NO4, 364.2488).
3.7.1. N-(trans-Crotonyl)-L-tyrosine (15a). Yield: 11.1 mg
(98%). Pale yellow gum. nmax (Nujol) 3600–3100, 3286,
1
1720, 1670 cmK1; H NMR (400 MHz, CD3OD) d 1.83
(3H, dd, JZ6.9, 1.7 Hz), 2.89 (1H, dd, JZ14.0, 8.7 Hz),
3.11 (1H, dd, JZ14.0, 5.2 Hz), 4.64 (1H, dd, JZ8.7,
5.2 Hz), 5.96 (1H, dq, JZ15.3, 1.7 Hz), 6.68 (2H, dt, JZ
8.5, 2.0 Hz), 6.75 (1H, dq, JZ15.3, 6.9 Hz), 7.03 (2H, dt,
JZ8.5, 2.0 Hz); 13C NMR (100 MHz, CD3OD) d 17.8, 37.8,
55.6, 116.1, 125.8, 129.2, 131.2, 141.3, 157.3, 168.3, 175.3;
(C)-HR-ESIMS m/z 250.1081 [MCH]C (calcd for
C13H16NO4, 250.1079).
3.7.7. N-(trans,trans-2,4-Hexadienoyl)-L-tyrosine (15g).
Yield: 17.0 mg (99%). Colourless oil. nmax (thin film)
3600–3100, 1719, 1656 cmK1
;
1H NMR (400 MHz,
CD3OD) d 1.82 (3H, d, JZ6.4 Hz), 2.90 (1H, dd, JZ14.0,
8.6 Hz), 3.11 (1H, dd, JZ14.0, 5.2 Hz), 4.66 (1H, dd,
JZ8.6, 5.2 Hz), 5.92 (1H, dd, JZ15.2, 0.4 Hz), 6.06–6.23
(2H, m), 6.69 (2H, dt, JZ8.6, 2.0 Hz), 7.03 (2H, dt, JZ8.6,
2.0 Hz), 7.08 (1H, dd, JZ15.5, 10.5 Hz); 13C NMR
(100 MHz, CD3OD) d 18.6, 37.8, 55.5, 116.2, 122.3,
129.1, 131.1, 131.2, 139.0, 142.7, 157.3, 168.8, 175.0;
(C)-HR-ESIMS m/z 276.1237 [MCH]C (calcd for
C15H18NO4, 276.1236).
3.7.2. N-(1-Oxopropyl)-L-tyrosine (15b). Yield: 10.1 mg
(96%). Pale yellow oil. nmax (thin film) 3600–3100, 1727,
1
1646 cmK1; H NMR (400 MHz, CD3OD) d 1.04 (3H, t,
JZ7.6 Hz), 2.17 (2H, qd, JZ7.6, 0.8 Hz), 2.84 (1H, dd, JZ
14.0, 9.1 Hz), 3.10 (1H, dd, JZ14.0, 5.1 Hz), 4.58 (1H, dd,
JZ9.1, 5.1 Hz), 6.69 (2H, dt, JZ8.6, 2.0 Hz), 7.03 (2H, dt,
JZ8.6, 2.0 Hz); 13C NMR (100 MHz, CD3OD) d 10.3, 29.9,
37.7, 55.3, 116.1, 129.2, 131.3, 157.3, 175.3, 176.8; (C)-
HR-ESIMS m/z 238.1072 [MCH]C (calcd for C12H16NO4,
238.1079).
3.7.8. N-Dodecanoylglycine (15h). Yield: 12.5 mg (98%).
White solid, mp 112–114 8C. nmax (Nujol) 3600–3100,
1
3.7.3. N-(trans-Cinnamoyl)-L-tyrosine (15c). Yield:
13.3 mg (98%). Colourless oil. nmax (thin film) 3600–
3318, 1703, 1644 cmK1; H NMR (400 MHz, CD3OD) d
0.90 (3H, t, JZ7.0 Hz), 1.24–1.32 (16H, m), 1.62 (2H, br tt,
JZ7.5, 7.5 Hz), 2.24 (2H, t, JZ7.5 Hz), 3.89 (2H, s); 13C
NMR (100 MHz, CD3OD) d 14.4, 23.7, 26.8, 30.3, 30.5,
30.6, 30.7, 33.1, 36.8, 41.8, 173.2, 176.7; (C)-HR-ESIMS
m/z 258.2067 [MCH]C (calcd for C14H28NO3, 258.2069).
1
3100, 1729, 1650 cmK1; H NMR (400 MHz, CD3OD) d
2.94 (1H, dd, JZ14.0, 8.5 Hz), 3.16 (1H, dd, JZ14.0,
5.2 Hz), 4.73 (1H, dd, JZ8.5, 5.2 Hz), 6.66 (1H, d, JZ
15.8 Hz), 6.70 (2H, dt, JZ8.6, 2.1 Hz), 7.07 (2H, dt, JZ8.6,