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A. R. Katritzky et al.
PAPER
13C NMR: d = 17.1, 37.4, 47.5, 55.9, 65.1, 126.2, 127.4, 127.6,
1H NMR (DMSO-d6): d = 0.83 (d, J = 6.2 Hz, 3 H), 0.88 (d, J = 6.3
Hz, 3 H), 1.21 (d, J = 7.2 Hz, 3 H), 1.52–1.62 (m, 3 H), 3.72 (d,
J = 5.1 Hz, 2 H), 4.02–4.07 (m, 1 H), 4.24–4.26 (m, 1 H), 4.99 (d,
J = 12.6 Hz, 1 H), 5.05 (d, J = 12.6 Hz, 1 H), 7.28–7.46 (m, 5 H),
7.55 (d, J = 7.0 Hz, 1 H), 7.90–7.97 (m, 1 H), 81.4–8.17 (m, 1 H).
13C NMR (DMSO-d6): d = 17.8, 21.3, 22.7, 24.1, 41.7, 50.1, 50.2,
65.4, 127.7, 127.7, 128.3, 136.8, 155.8, 168.6, 172.7, 173.8.
128.0, 128.3, 129.2, 137.0, 138.2, 155.8, 171.4, 174.0.
(2S)-2-[((2S)-2-{[(Benzyloxy)carbonyl]amino}-3-phenylpro-
panoyl)amino]-3-methylbutanoic Acid (Z-Phe-Val-OH, 2g)31
Colorless microcrystals (95%); mp 140–142 °C (Lit.31 mp 149–
151 °C); [a]D25 –6.2 (c = 2.0, MeOH) {(Lit.31 [a]D22 –6.3 (c = 2.0,
MeOH)}.
1H NMR (DMSO-d6): d = 0.90 (d, J = 5.2 Hz, 6 H, 2 CH3), 2.05–
2.11 [m, 1 H, CHCH(CH3)2], 2.69–2.77 (m, 1 H, CHCH2Ph), 2.98–
3.02 (m, 1 H, CHCH2Ph), 4.17–4.22 (m, 1 H, NCHCO), 4.36–4.41
(m, 1 H, NCHCO), 4.94 (s, 2 H, OCH2Ph), 7.19–7.53 (m, 11 H, ArH
and NH), 8.07–8.09 (m, 2 H, NH and CO2H).
Anal. Calcd for C19H27N3O6: C, 58.00; H, 6.92; N, 10.68. Found: C,
58.43; H, 6.99; N, 10.66.
(5S,11S)-11-Isobutyl-5-isopropyl-3,6,9-trioxo-1-phenyl-2-oxa-
4,7,10-triazadodecan-12-oic Acid (Z-Val-Gly-Leu-OH, 4b)
Colorless microcrystals (85%); mp 131.5–132.5 °C; [a]D25 –17.1
(c = 1.4, MeOH).
1H NMR (DMSO-d6): d = 0.82–0.88 (m, 12 H, 4 CH3), 1.49–1.66
[m, 3 H, CH2CH(CH3)2], 1.93–2.02 [m, 1 H, CHCH(CH3)2], 3.73
(d, J = 5.4 Hz, 2 H, NCH2CO), 3.85 (apparent t, J = ca. 7.7 Hz, 1 H,
NCHCO), 4.25 (apparent q, J = ca. 7.7 Hz, 1 H, NCHCO), 5.01 (d,
J = 12.6 Hz, 1 H, OCH2Ph), 5.07 (d, J = 12.6 Hz, 1 H, OCH2Ph),
7.30–7.40 (m, 6 H, ArH and NH), 7.95 (d, J = 8.0 Hz, 1 H, NH),
8.21 (t, J = 5.4 Hz, 1 H, NH); one exchangeable proton is missing.
13C NMR (DMSO-d6): d = 17.9, 19.0, 29.9, 37.3, 55.8, 57.1, 65.1,
126.1, 127.3, 127.6, 127.9, 128.2, 129.1, 136.9, 138.0, 155.7, 171.8,
172.8.
(2S)-2-[((2S)-2-{[(Benzyloxy)carbonyl]amino}-3-phenylpro-
panoyl)amino]-3-phenylpropanoic Acid (Z-Phe-Phe-OH,
2h)32,33
Colorless microcrystals (98%); mp 141–142 °C (Lit.33 mp 138–
139 °C); [a]D25 –6.7 (c = 1.3, MeOH).
13C NMR (DMSO-d6): d = 18.1, 19.1, 21.3, 22.7, 24.1, 29.9, 41.6,
50.0, 60.3, 65.3, 127.6, 127.7, 128.2, 136.9, 156.2, 168.5, 171.4,
173.8.
1H NMR (DMSO-d6): d = 2.67–2.75 (m, 1 H, CHCH2Ph), 2.93–
3.14 (m, 3 H, CHCH2Ph), 4.31–4.34 (m, 1 H, NCHCO), 4.49–4.5.1
(m, 1 H, NCHCO), 4.94 (s, 2 H, OCH2Ph), 7.12–7.51 (m, 16 H),
8.10 (br s, 1 H, CO2H), 8.32 (d, J = 7.6 Hz, 1 H, NH).
13C NMR (DMSO-d6): d = 36.6, 37.3, 53.4, 55.9, 65.1, 126.1, 126.4,
127.3, 127.6, 127.9, 128.1, 128.2, 129.1, 136.9, 137.3, 138.0, 155.7,
171.5, 172.7.
Anal. Calcd for C21H31N3O6: C, 59.84; H, 7.41; N, 9.97. Found: C,
60.13; H, 7.64; N, 9.94.
(5S)-5-Benzyl-3,6,9-trioxo-1-phenyl-2-oxa-4,7,10-triazadode-
can-12-oic Acid (Z-Phe-Gly-Gly-OH, 4c)35
Colorless microcrystals (98%); mp 120–122 °C (Lit.35 mp 122–
125 °C); [a]D25 –21.4 (c = 1.4, DMF) {Lit.35 [a]D15 –11.8 (c = 1.0,
DMF)}.
(2S)-2-[((2S)-2-{[(Benzyloxy)carbonyl]amino}-3-phenylpro-
panoyl)amino]-3-hydroxypropanoic Acid (Z-Phe-Ser-OH, 2i)34
Colorless microcrystals (96%); mp 140–141 °C (Lit.34 mp 137 °C);
[a]D25 +0.6 (c = 1.0, MeOH) {Lit.34 [a]D22 +0.6 (c = 1.0, MeOH)}.
1H NMR (DMSO-d6): d = 2.73 (t, J = 12.6 Hz, 1 H, CHCH2Ph),
3.06–3.10 (m, 1 H, CHCH2Ph), 3.67 (dd, J = 10.3, 3.3 Hz, 1 H,
CHCH2OH), 3.78 (dd, J = 10.3, 4.5 Hz, 1 H, CHCH2OH), 4.32–
4.42 (m, 2 H, 2 NCHCO), 4.93 (s, 2 H, OCH2Ph), 7.24–7.46 (m, 10
H), 7.52 (d, J = 8.8 Hz, 1 H, NH), 8.32 (d, J = 7.7 Hz, 1 H, NH); two
exchangeable protons (OH and CO2H) are missing.
1H NMR (DMSO-d6): d = 2.76 (t, J = 12.3 Hz, 1 H, CHCH2Ph),
3.03–3.08 (m, 1 H, CHCH2Ph), 3.78 (s, 4 H, 2 NCH2CO), 4.31 (br
s, 1 H, NCHCO), 4.94 (s, 2 H, OCH2Ph), 7.25–7.40 (m, 11 H, ArH
and NH), 7.56 (d, J = 7.8 Hz, 1 H, NH), 8.11 (br s, 1 H, NH), 8.35
(br s, 1 H, CO2H).
13C NMR (DMSO-d6): d = 37.4, 40.6, 41.9, 56.2, 65.3, 126.2, 127.4,
127.6, 128.0, 128.3, 129.2, 137.0, 138.1, 155.9, 169.0, 171.1, 171.8.
13C NMR (DMSO-d6): d = 37.4, 54.6, 55.9, 61.2, 65.1, 126.1, 127.3,
(5S,8S,11S)-5-Benzyl-8,11-dimethyl-3,6,9-trioxo-1-phenyl-2-
oxa-4,7,10-triazadodecan-12-oic Acid (Z-Phe-Ala-Ala-OH,
4d)36
127.6, 127.9, 128.2, 129.2, 136.9, 138.1, 155.7, 171.7, 171.8.
(5S,11S)-11-Isobutyl-5-methyl-3,6,9-trioxo-1-phenyl-2-oxa-
4,7,10-triaza-dodecan-12-oic Acid (Z-Ala-Gly-Leu-OH, 4a)
Colorless microcrystals (93%); mp 150.5–151.5 °C; [a]D25 –13.8
(c = 1.3, MeOH).
1H NMR (DMSO-d6): d = 0.83 (d, J = 6.2 Hz, 3 H, CH3), 0.87 (d,
J = 6.3 Hz, 3 H, CH3), 1.20 (d, J = 7.2 Hz, 3 H, CH3), 1.52–1.64 [m,
3 H, CH2CH(CH3)2], 3.72 (d, J = 5.4 Hz, 2 H, NCH2CO), 4.02–4.07
(m, 1 H, NCHCO), 4.21–4.29 (m, 1 H, NCHCO), 4.99 (d, J = 12.6
Hz, 1 H, OCH2Ph), 5.06 (d, J = 12.6 Hz, 1 H, OCH2Ph), 7.36 (s, 5
H), 7.55 (d, J = 7.0 Hz, 1 H, NH), 7.91 (d, J = 7.8 Hz, 1 H, NH),
8.17 (br s, 1 H, NH); one exchangeable proton is missing.
Colorless microcrystals (92%); mp 180–181 °C (Lit.36 mp 187.5–
188.5 °C); [a]D25 –15.0 (c = 1.0, DMF).
1H NMR (DMSO-d6): d = 1.23–1.29 (m, 6 H, 2 CH3), 2.66–2.75 (m,
1 H, CHCH2Ph), 3.00–3.05 (m, 1 H, CHCH2Ph), 4.17–4.35 (m, 3 H,
3 NCHCO), 4.93 (s, 2 H, OCH2Ph), 7.19–7.33 (m, 10 H), 7.51 (d,
J = 8.7 Hz, 1 H, NH), 8.14 (br s, 1 H, NH), 8.17 (br s, 1 H, NH); one
exchangeable proton is missing.
13C NMR (DMSO-d6): d = 17.1, 18.2, 37.3, 47.4, 47.8, 55.9, 65.1,
126.1, 127.3, 127.5, 127.9, 128.2, 129.1, 136.9, 138.1, 155.8, 171.1,
171.7, 173.9.
13C NMR (DMSO-d6): d = 17.8, 21.3, 22.7, 24.1, 41.7, 50.0, 65.3,
(5S,8S,11S)-5-Benzyl-11-(hydroxymethyl)-8-methyl-3,6,9-tri-
oxo-1-phenyl-2-oxa-4,7,10-triazadodecan-12-oic Acid (Z-Phe-
Ala-Ser-OH, 4e)
127.7, 127.7, 128.2, 136.8, 155.7, 168.5, 172.6, 173.8.
Anal. Calcd for C19H27N3O6: C, 58.00; H, 6.92; N, 10.68. Found: C,
58.21; H, 7.01; N, 10.59.
Colorless microcrystals (94%); mp 185.5–186.5 °C; [a]D25 –1.4 (c =
1.1, DMF).
(11S)-11-Isobutyl-5-methyl-3,6,9-trioxo-1-phenyl-2-oxa-4,7,10-
triazadodecan-12-oic Acid (Z-DL-Ala-Gly-Leu-OH, 4a + 4a¢)
Colorless microcrystals (94%); mp 101–105 °C.
1H NMR (DMSO-d6): d = 1.26 (d, J = 7.0 Hz, 3 H, CHCH3), 2.68–
2.76 (m, 1 H, CHCH2Ph), 3.01–3.10 (m, 1 H, CHCH2Ph), 3.62–3.76
(m, 2 H, CHCH2OH), 4.24–4.34 (m, 2 H, 2 NCHCO), 4.26–4.48 (m,
1 H, NCHCO), 4.92–4.94 (m, 2 H, OCH2Ph), 7.20–7.34 (m, 10 H),
Synthesis 2004, No. 16, 2645–2652 © Thieme Stuttgart · New York