CHa Val3), 4.50–4.27 (4H, m, CHa Ala1, CHa Val2, CH2 Fmoc),
4.27–4.15 (1H, m, CH Fmoc), 2.60–2.40 (3H, m, CHiPr Val2,
–COCH2CH3), 2.25–2.10 (1H, m, CHiPr Val3), 1.36 (3H, d, J 6.0,
CH3 Ala1), 1.21 (3H, t, J 7.4, –COCH2CH3), 0.99 (6H, d, J 6.1,
CH3 Val2), 0.91 (3H, d, J 6.8, CH3 Val3), 0.86 (3H, d, J 6.8, CH3
HRMS (ESI +) m/z: found, 764.3894; C43H55N3O8Na requires
764.3887.
Fmoc–Ala1–W[CO–N(OCOPh)]–D-Val2–Val3–OBn (17). The
title compound was prepared from (S,R,S)-5 and benzoic acid
using method B (93% yield) or benzoic chloride using method C
(83% yield). Eluent for flash chromatography: pentane–EtOAc 9
=
Val3). dC (75 MHz; CDCl3) 173.4, 172.3, 171.4, 167.9 (C O), 155.5
=
(C O Fmoc), 144.1, 143.9, 141.4 (2 peaks) (Car Fmoc), 135.6 (Car
25
: 1 to 1 : 1; colourless oil. Rf 0.76 (CH2Cl2–MeOH 95 : 5). [a]D
–OBn), 128.6, 128.4, 127.8, 127.2, 125.3, 125.2, 120.1 (CHar), 67.2
(CH2 Fmoc), 67.1 (2 peaks) (CH2 –OBn, CHa Val2), 57.5 (CHa
Val3), 47.7 (CHa Ala1), 47.3 (CH Fmoc), 31.3 (CHiPr Val3), 27.0
(CHiPr Val2), 25.3 (–COCH2–), 19.7, 19.1, 19.0, 17.8 (CH3), 8.7
(–COCH2CH3). IR: 3338, 2966, 1802, 1724, 1664, 1529, 1451,
1245, 1060, 740. LRMS (DCI) m/z: 689.1 (M + NH4)+. HRMS
(ESI +) m/z: found, 672.3292; C38H46N3O8 requires 672.3285.
+26.9◦ (c 1.06 in CHCl3). dH (300 MHz; CDCl3) 8.12–8.00 (3H, m,
CHar), 7.77–7.25 (16H, m, CHar, NH Val3), 5.75 (1H, d, J 7.8, NH
Ala1), 5.15 (2H, ABq, J 12.6, dA − dB 10.1, CH2 –OBn), 4.63–4.45
(2H, m, CHa Ala1, CHa Val3), 4.39–4.26 (3H, m, CHa Val2, CH2
Fmoc), 4.21–4.11 (1H, m, CH Fmoc), 2.70–2.55 (1H, m, CHiPr
Val2), 2.30–2.15 (1H, m, CHiPr Val3), 1.37 (3H, d, J 6.4, CH3 Ala1),
1.08 (3H, d, J 6.7, CH3 Val2), 1.02 (3H, d, J 6.8, CH3 Val2), 0.94
(3H, d, J 6.8, CH3 Val3), 0.90 (3H, d, J 6.8, CH3 Val3). dC (75 MHz;
Fmoc–Ile1–W[CO–N(OCOtBu)]–D-Val2–Val3–OBn (15). The
title compound was prepared from (S,R,S)-4 and trimethylacetic
anhydride using method A. Eluent for flash chromatography:
CH2Cl2–MeOH 99.75 : 0.25 to 95 : 5; colourless oil, 87% yield. Rf
=
=
=
CDCl3) 171.6 (C O Ala1), 171.0 (C O Val3), 168.0 (C O Val2),
=
164.9 (COPh), 155.6 (C O Fmoc), 144.1, 143.9, 141.4 (Car Fmoc),
135.6 (Car Ph), 135.0 (Car –OBn), 133.7, 130.5, 129.7, 129.1, 128.8,
128.7, 128.6, 128.5, 128.4, 127.9, 127.2, 126.2, 125.4, 125.3, 120.1
(CHar), 67.3, 67.1 (CHa Val2, CH2 –OBn, CH2 Fmoc), 57.6 (CHa
Val3), 48.0 (CHa Ala1), 47.3 (CH Fmoc), 31.3 (CHiPr Val3), 27.2
(CHiPr Val2), 19.9, 19.5 (CH3), 19.2 (CH3 Ala1), 18.9, 17.8 (CH3).
IR: 3334, 2965, 1773, 1718, 1666, 1539, 1451, 1236, 1006, 705.
HRMS (ESI +) m/z: found, 742.3105; C42H45N3O8Na requires
742.3104.
0.71 (CH2Cl2–MeOH 95 : 5). [a]D +31.3◦ (c 3.08 in CHCl3). dH
25
(300 MHz; CDCl3) 7.73 (2H, d, J 7.2, CHar Fmoc), 7.57 (1H, d, J
7.2, CHar Fmoc), 7.51 (1H, d, J 7.2, CHar Fmoc), 7.43–7.14 (10H,
m, CHar, NH Val3), 5.47 (1H, d, J 9.1, NH Ile1), 5.07 (2H, ABq,
J 12.1, dA − dB 26.9, CH2 –OBn), 4.48 (1H, dd, J 4.7 and 7.7,
CHa Val3), 4.43–4.03 (5H, m, CHa Ile1, CHa Val2, CH Fmoc, CH2
Fmoc), 2.53–2.37 (1H, m, CHiPr Val2), 2.23–2.09 (1H, m, CHiPr
Val3), 1.89–1.60 (1H, m, CHsBu Ile1), 1.59–1.41 (1H, m, CHH Ile1),
1.34 (9H, s, CH3 tBu), 1.16–0.70 (19H, m, CHH Ile1, CH3 Ile1,
CH3 Val2, CH3 Val3). dC (75 MHz; CDCl3) 175.7, 173.1, 171.4,
Fmoc–Ala1–W[CO–N(OCOPh)]–D-Ala2–Val3–OEt (18). The
title compound was prepared from (S,R,S)-7 and benzoic acid
using method D. Eluent for flash chromatography: pentane–
EtOAc 3 : 1; pale yellow oil, 60% yield. Rf 0.33 (pentane–EtOAc 3 :
=
=
167.9 (C O), 156.2 (C O Fmoc), 144.2, 143.9, 141.5 (Car Fmoc),
135.8 (Car –OBn), 128.6, 128.4, 127.8, 127.2, 125.4, 120.1 (CHar),
67.1, 66.9 (CHa Val2, CH2 Fmoc, CH2 –OBn), 57.6 (CHa Val3),
25
1). [a]D +24.75 (c 0.99 in CHCl3). dH (300 MHz; CDCl3) 8.11 (2H,
d, J 7.2, CHar Fmoc), 7.76 (2H, d, J 7.5, CHar Fmoc), 7.70–7.30
(10H, m, CHar Fmoc, Ph, NH Val3), 5.63 (1H, d, J 7.5, NH Ala1),
4.95 (1H, q, J 7.4, CHa Ala2), 4.65–4.45 (2H, m, CHa Ala1, CHa
Val3), 4.40–4.00 (5H, m, CH2 Fmoc, CH Fmoc, CH2 –OEt), 2.35–
2.10 (1H, m, CHiPr Val3), 1.52 (3H, d, J 7.2, CH3 Ala2), 1.42 (3H,
d, J 6.8, CH3 Ala1), 1.35–1.10 (3H, m, CH3 –OEt), 0.97 (3H, d, J
6.5, CH3 Val3), 0.94 (3H, d, J 6.8, CH3 Val3). dC (75 MHz, CDCl3)
t
55.6 (CHa Ile1), 47.4 (CH Fmoc), 38.6, 38.4 (C Bu, CHiPr Val2),
31.6 (CHiPr Val3), 27.2, 27.0 (CH3 Bu), 26.1 (CHsBu Ile1), 24.1 (CH2
t
Ile1), 19.9, 19.4, 19.2, 17.8, 15.7 (CH3), 11.4 (CH3 Ile1). IR: 3342,
2966, 1795, 1732, 1661, 1520, 1228, 740. HRMS (ESI +) m/z:
found, 742.4061; C43H56N3O8 requires 742.4067.
Fmoc–Ile1–W[CO–N(OCOtBu)]–Val2–Val3–OBn
(16). The
=
=
=
171.8, 169.3 (C O), 165.6 (C O Ph), 155.7 (C O Fmoc), 144.0,
143.9, 141.4 (Car Fmoc), 135.2 (Car Ph), 130.6, 129.2, 127.9, 127.2,
125.3, 120.1 (CHar), 67.3 (CH2 Fmoc), 61.2 (CH2 –OEt), 59.2
(CHa Ala2), 57.8 (CHa Val3), 47.8 (CHa Ala1), 47.2 (CH Fmoc),
31.1 (CHiPr Val3), 19.2 (CH3 Val3), 18.2 (CH3 Ala1), 17.9 (CH3
Val3), 14.3 (CH3 –OEt), 13.4 (CH3 Ala2). IR: 3350, 2957, 2928,
1765, 1683, 1534, 1447, 1232, 1009, 703. HRMS (ESI +) m/z:
found, 652.2635; C35H39N3O8Na requires 652.2635.
title compound was prepared from (S,S,S)-4 and trimethylacetic
anhydride using method A. Eluent for flash chromatography:
pentane–EtOAc 9 : 1 to 1 : 1; colourless oil, 15% yield. Rf 0.66
(CH2Cl2–MeOH 95 : 5). [a]D −38.8◦ (c 2.46 in CHCl3). dH
25
(300 MHz; CDCl3) 7.74 (2H, d, J 7.2, CHar Fmoc), 7.56 (2H, d, J
6.8, CHar Fmoc), 7.45–7.15 (10H, m, CHar, NH Val3), 5.42 (1H, d,
J 9.1, NH Ile1), 5.12 (2H, ABq, J 11.9, dA − dB 21.9, CH2 –OBn),
4.69–4.46 (1H, m, CHa Val3), 4.45–4.25 (3H, m, CHa Ile1, CH2
Fmoc), 4.24–4.00 (2H, m, CHa Val2, CH Fmoc), 2.55–2.40 (1H,
m, CHiPr Val2), 2.25–2.10 (1H, m, CHiPr Val3), 1.90–1.70 (1H, m,
CHsBu Ile1), 1.64–1.48 (1H, m, CHH Ile1), 1.36 (9H, s, CH3 tBu),
1.16–0.80 (19H, m, CHH Ile1, CH3 Ile1, CH3 Val2, CH3 Val3). dC
=
Fmoc–Ala1–W[ CO–N( OCO( CH2 )2CH CH2 ) ]–D-Val2–Val3–
OBn (19). The title compound was prepared from (S,R,S)-5 and
4-pentenoic acid using method B. Eluent for flash chromatog-
raphy: pentane–EtOAc 9 : 1 to 1 : 1; colourless oil, 93%. Rf
(75 MHz; CDCl3) 176.3, 172.6, 171.8, 167.5 (C O), 156.2 (C O
Fmoc), 144.1, 143.9, 141.5 (Car Fmoc), 135.7 (Car –OBn), 128.8,
128.7, 128.6, 128.4, 127.9, 127.2, 125.3, 120.1 (CHar), 67.2, 67.0
(CHa Val2, CH2 Fmoc, CH2 –OBn), 57.6 (CHa Val3), 55.3 (CHa
Ile1), 47.3 (CH Fmoc), 38.6 (C tBu), 37.1 (CHsBu Ile1), 31.0 (CHiPr
Val3), 27.6 (CHiPr Val2), 27.0 (CH3 tBu), 23.7 (CHsBu Ile1), 20.2
(CH2 Ile1), 19.4, 19.1, 19.0, 17.8 (CH3 Val), 16.0, 11.2 (CH3 Ile1).
IR: 3345, 2964, 1793, 1724, 1691, 1651, 1524, 1236, 1065, 741.
0.73 (CH2Cl2–MeOH 95 : 5). [a]D +12.9◦ (c 1.87 in CHCl3). dH
25
=
=
(300 MHz; CDCl3) 7.75 (2H, d, J 7.6, CHar Fmoc), 7.58 (2H, dd,
J 7.3 and 7.3, CHar Fmoc), 7.45–7.25 (10H, m, CHar, NH Val3),
=
5.95–5.72 (1H, m, –CH CH2), 5.69 (1H, d, J 7.7, NH Ala1),
=
5.20–4.95 (4H, m, CH2 –OBn, –CH CH2), 4.51 (1H, dd, J 5.0
and 8.3, CHa Val3), 4.49–4.25 (4H, m, CHa Val2, CHa Ala1, CH2
Fmoc), 4.24–4.16 (1H, m, CH Fmoc), 2.65–2.35 (5H, m, CHiPr
Val2, –COCH2CH2–), 2.25–2.00 (1H, m, CHiPr Val3), 1.34 (3H, d,
3136 | Org. Biomol. Chem., 2006, 4, 3125–3141
This journal is
The Royal Society of Chemistry 2006
©