M. Tullberg et al. / Tetrahedron 62 (2006) 7484–7491
7489
(m, 1H, a-CH), 2.97–2.91 (m, 2H, CH2-Ph), 1.15–1.04 (m,
3H, CHCH2-Nle and CH2CH3-Nle), 0.91–0.82 (m, 2H,
CH2CH2-Nle), 0.78 (dt, J¼7.3, 1.8 Hz, 3H, CH3-Nle), 0.53–
0.47 (m, 1H, CHCH2-Nle). 13C NMR (CD3OD) d 168.8,
167.6 (C]O, amides), 135.4 (C-10), 130.4, 128.2 (C-20 and
C-30), 127.1 (C-40), 56.0, 54.6 (a-CH), 38.7 (CH2-Ph), 33.8
(CHCH2-Nle), 26.4 (CH2CH2-Nle), 21.9 (CH2CH3-Nle),
12.9 (CH3-Nle). Anal. Calcd for C15H20N2O2: C, 69.20;
H, 7.74; N, 10.76; Found C, 68.9; H, 7.6; N, 10.9.
1.04 (d, J¼7.3 Hz, 3H, CH3-Val), 0.94 (d, J¼7.3 Hz, 3H,
CH3-Val), 0.93 (t, J¼7.0 Hz, 3H, CH3-Nle). 13C NMR
(CD3OD) d 169.5, 168.4 (C]O, amides), 60.1, 54.6
(a-CH), 34.1, 32.0 (CH-Val and CHCH2-Nle), 27.1
(CH2CH2-Nle), 22.1 (CH2CH3-Nle), 17.9, 16.3 (CH3-Val),
12.9 (CH3-Nle). Anal. Calcd for C11H20N2O2: C, 62.23; H,
9.50; N, 13.20; Found C, 62.4; H, 9.8; N, 13.5.
4.3.8. c(D-Valinyl-L-norleucinyl) (30).31 Compound 19 and
triethylamine were reacted as described in the general proce-
dure (Section 4.3). The crude product had to be purified
by flash chromatography using CH2Cl2/CH3OH (95:5) as
eluent. Pure 30 was isolated as white crystals.
4.3.5. c(L-Phenylalaninyl-L-leucinyl) (27). Compound 16
and triethylamine were reacted as described in the general
procedure (Section 4.3). Pure 27 was isolated as white crys-
tals.
Mp 263–265 ꢀC. [a]D ꢂ6.6 (c 0.3, CH3OH). IR (KBr) nmax
1
Mp 282–284 ꢀC. [a]D ꢂ8.0 (c 0.3, CH3OH). IR (KBr) nmax
3324, 3019, 1776, 1589 cmꢂ1. H NMR (CD3OD) d 4.04
3430, 3012, 1666, 1570, 1389 cmꢂ1 21,30
.
1H NMR
(td, J¼4.8, 1.1 Hz, 1H, a-CH), 3.79 (dd, J¼3.7, 1.1 Hz,
1H, a-CH), 2.32–2.24 (m, 1H, CH-Val), 1.96–1.86 (m, 1H,
CHCH2-Nle), 1.80–1.71 (m, 1H, CHCH2-Nle), 1.39–1.27
(m, 4H, CH2-Nle), 1.03 (d, J¼7.0 Hz, 3H, CH3-Val),
0.94 (d, J¼7.0 Hz, 3H, CH3-Val), 0.92 (t, J¼7.0 Hz,
3H, CH3-Nle). 13C NMR (CD3OD) d 169.6, 169.0 (C]O,
amides), 60.2, 54.0 (a-CH), 32.8, 32.2 (CH-Val and
CHCH2-Nle), 25.7 (CH2CH2-Nle), 22.2 (CH2CH3-Nle),
17.5, 15.7 (CH3-Val), 12.9 (CH3-Nle). Anal. Calcd for
C11H20N2O2: C, 62.23; H, 9.50; N, 13.20; Found C, 62.0;
H, 9.8; N, 13.5.
(CDCl3) d 7.36–7.18 (m, 5H, Ph-H), 4.28–4.24 (m, 1H,
a-CH), 3.90–3.85 (m, 1H, a-CH), 3.28–3.22 (m, 1H,
CH2-Ph), 3.09–3.02 (m, 1H, CH2-Ph), 1.54 (app s, 2H,
CH2-Leu), 1.24 (app s, 1H, CH-Leu), 0.86 (app t,
J¼6.2 Hz, 6H, CH3-Leu). 13C NMR (CDCl3) d 171.6,
168.0 (C]O, amides), 135.1 (C-10), 129.9, 129.2 (C-20
and C-30), 127.7 (C-40), 56.3, 53.3 (a-CH), 42.9 (CH2-Leu),
40.3 (CH2-Ph), 24.1 (CH-Leu), 23.2, 20.9 (CH3-Leu). Anal.
Calcd for C15H20N2O2: C, 69.20; H, 7.74; N, 10.76; Found
C, 69.0; H, 7.8; N, 10.5.
4.3.6. c(L-Tryptophanyl-L-asparginyl) (28). Compound 17
and triethylamine were reacted as described in the general
procedure (Section 4.3). Pure 28 was isolated as off-white
crystals.
4.3.9. c(Glycinyl-L-norleucinyl) (31).32 Compound 20 and
triethylamine were reacted as described in the general proce-
dure (Section 4.3). Pure 31 was isolated as fluffy white
crystals.
Mp 272–274 ꢀC. [a]D ꢂ36 (c 0.2, DMSO). IR (KBr) nmax
Mp 256 ꢀC. [a]D ꢂ1.4 (c 1, DMSO). IR (KBr) nmax 3200,
3450, 3207, 3048, 1672, 1559, 1507 cmꢂ1
.
1H NMR
2954, 1682, 1468, 1337 cmꢂ1 1H NMR (DMSO-d6)
.
(DMSO-d6) d 10.90 (s, 1H, NH, indole), 7.94 (d,
J¼1.8 Hz, 1H, NH, amide), 7.67 (d, J¼1.5 Hz, 1H, NH,
amide), 7.57 (d, J¼7.7 Hz, 1H, indole), 7.12 (s, 1H, indole),
7.05 (t, J¼7.0 Hz, 1H, indole), 6.96 (t, J¼7.5 Hz, 1H,
indole), 6.91 (d, J¼7.7 Hz, 1H, indole), 4.13 (t, J¼4.2 Hz,
1H, a-CH), 3.99 (dd, J¼7.0, 3.7 Hz, 1H, a-CH), 3.21 (dd,
J¼14.5, 4.6 Hz, 1H, CH2-indole), 3.10 (dd, J¼14.5,
4.6 Hz, 1H, CH2-indole), 2.18 (dd, J¼15.7, 4.4 Hz, 1H,
CH2-Asn), 1.48 (dd, J¼15.7, 8.1 Hz, 1H, CH2-Asn). 13C
NMR (DMSO-d6) d 172.0 (C]O, Asn), 167.8, 167.5
(C]O, amides), 136.5 (C-7a), 128.2 (C-3a), 125.0 (C-2),
121.4, 119.4, 119.0 (C-4, C-5 and C-6), 111.8, 109.4
(C-3 and C-7), 55.8 (a-CH, Trp), 51.9 (a-CH, Asn),
38.8 (CH2-Asn), 29.2 (CH2-indole). Anal. Calcd for
C15H16N4O3: C, 59.99; H, 5.37; N, 18.66; Found C, 59.9;
H, 5.6; N, 18.3.
d 8.18 (s, 1H, NH-amide), 7.98 (s, 1H, NH-amide), 3.81–
3.63 (m, 3H, CH2-Gly and a-CH), 1.71–1.61 (m, 2H,
CHCH2-Nle), 1.33–1.23 (m, 4H, CH2-Nle), 0.87 (t,
J¼7.4 Hz, 3H, CH3-Nle). 13C NMR (DMSO-d6) d 168.6,
166.6 (C]O, amides), 54.7 (a-CH), 44.8 (CH2-Gly), 33.2
(CHCH2-Nle), 26.8 (CH2CH2-Nle), 22.5 (CH2CH3-Nle),
14.4 (CH3-Nle). Anal. Calcd for C8H14N2O2: C, 56.45; H,
8.29; N, 16.46; Found C, 56.5; H, 8.3; N, 16.1.
4.3.10. c(L-Leucinyl-L-tyrosinyl) (32). Compound 21 and
triethylamine were reacted as described in the general proce-
dure (Section 4.3). Pure 32 was isolated as white crystals.
33
ꢀ
Mp 301–303 ꢀC (lit. mp 295–296 C). [a]D 33.3 (c 0.3,
CH3OH). IR (KBr) nmax 3306, 3206, 2953, 1667,
1467 cmꢂ1. H NMR (CD3OD) d 6.99 (d, J¼8.4 Hz, 2H,
1
Ph-H), 6.70 (d, J¼8.4 Hz, 2H, Ph-H), 4.22 (t, J¼4.0 Hz,
1H, a-CH), 3.65 (dd, J¼10.0, 4.2 Hz, 1H, a-CH), 3.19
(dd, J¼13.5, 3.7 Hz, 1H, CH2-Ph), 2.81 (dd, J¼13.5,
3.7 Hz, 1H, CH2-Ph), 1.47–1.36 (m, 1H, CH-Leu), 0.87
(ddd, J¼13.8, 9.6, 4.4 Hz, 1H, CH2-Leu), 0.73 (app t,
J¼8.1 Hz, 6H, CH3-Leu), 0.10 (ddd, J¼13.8, 9.6, 4.4 Hz,
1H, CH2-Leu). 13C NMR (CD3OD) d 171.4, 167.6 (C]O,
amides), 157.0 (C-40), 131.4 (C-20), 125.7 (C-10), 115.1
(C-30), 56.3, 52.8 (a-CH), 43.9 (CH2-Leu), 38.1 (CH2-Ph),
23.3 (CH-Leu), 22.1, 20.0 (CH3-Leu). Anal. Calcd for
C15H20N2O3: C, 65.20; H, 7.30; N, 10.14; Found C, 65.1;
H, 7.3; N, 9.9.
4.3.7. c(L-Valinyl-L-norleucinyl) (29).31 Compound 18 and
triethylamine were reacted as described in the general proce-
dure (Section 4.3). The crude product had to be purified
by flash chromatography using CH2Cl2/CH3OH (95:5) as
eluent. Pure 29 was isolated as white crystals.
Mp 254–256 ꢀC. [a]D ꢂ87.7 (c 0.4, CH3OH). IR (KBr) nmax
1
3310, 3019, 1800, 1640 cmꢂ1. H NMR (CD3OD) d 3.96–
3.93 (m, 1H, a-CH), 3.83–3.81 (m, 1H, a-CH), 2.30–2.22
(m, 1H, CH-Val), 1.87–1.82 (m, 1H, CHCH2-Nle), 1.79–
1.74 (m, 1H, CHCH2-Nle), 1.43–1.32 (m, 4H, CH2-Nle),