SYNTHESIS OF CHIRAL LIPOPHILIC AMINO ACIDS
& H5), 1.44 (s, 9H, H200), 1.58–1.94 (m, 2H, H3), 4.12 (m, 1H, H2,
rotamer A), 4.30 (m, 1H, H2 rotamer B), 5.01 (bs, 1H, NH rotamer
B), 6.21 (bs, 1H, NH rotamer A), 8.30 (bs, 1H, OH). 13C nmr
(100 MHz, CDCl3): d 13.9 (C6), 22.4 (C5), 27.5 (C4), 28.5 (C200), 33.3
(C3), 53.6 (C2), 80.3 (C100), 155.8 (C10), 177.8 (C1). HRMS (ESIꢀ,
MeOH): m/z 230.1394 (M ꢀ H)¯, C11H20NO4¯ requires 230.1398.
(2H, m, H3), 4.22 (1H, t, J = 6.8 Hz, H2), 4.37–4.48 (1H, m, CH),
4.41 (2H, d, J = 6.8 Hz, CH2), 5.30 (1H, d, J = 8.4 Hz, NH), 7.30
(t, J = 7.4 Hz, 2H, H20 & H70), 7.39 (t, J = 7.4 Hz, 2H, H30 & H60),
7.57–7.60 (m, 2H, H10 & H80), 7.75 (d, J = 7.4 Hz, 2H, H40 & H50),
OH not observed. 13C nmr (100 MHz, CDCl3): d 14.2 (C10), 22.8,
25.4, 29.31, 29.35, 29.5, 32.0, 32.5, 47.3, 54.0, 67.2, 120.1, 125.2,
127.2, 127.9, 141.5, 143.9 & 144.0 (C80a & C90a), 156.3 (OCONH),
177.5 (C1). LC-MS: 25 tR = 5.48 min (>98% pure), (ESI+, MeOH):
m/z 432.1 (M + Na)+, C25H31NO4Na requires 432.22.
Compound 22
The titled compound was obtained as a colourless solid (93.5 mg,
86%), mp 111–112 ꢂC. nmax (neat): 3376m, 2920s, 2853s, 1751s,
1734s, 1671s, 1560s, 1457s, 1377m, 1268m, 1181m, 1167m,
1124m, 1044w, 739m, 734m. 1H nmr (400 MHz, CDCl3): d 0.89
(3H, t, J = 6.4 Hz, H7), 1.26–1.38 (6H, m, H4–6), 1.66–1.94 (2H, m,
H3), 4.23 (1H, t, J = 6.8 Hz, H2), 4.38–4.45 (1H, m, CH), 4.42
(2H, d, J = 6.8 Hz, CH2), 5.26 (1H, d, J = 7.6 Hz, NH), 7.31
(t, J = 7.4 Hz, 2H, H20 & H70), 7.40 (t, J = 7.4 Hz, 2H, H30 & H60),
7.58–7.61 (m, 2H, H10 & H80), 7.76 (d, J = 7.4 Hz, 2H, H40 & H50),
OH not observed. 13C nmr (100 MHz, CDCl3): d 14.1 (C7), 22.5,
25.0, 31.4, 32.4, 47.3, 54.0, 67.2, 120.1, 125.2, 127.2, 127.9, 141.5,
143.8 & 144.0 (C80a & C90a), 156.2 (OCONH), 177.4 (C1). LC-MS:
22 tR = 5.55 min (>98% pure), (ESI+, MeOH): m/z 390.1(M + Na)+,
C22H25NO4Na requires 390.17.
Compound 26
The titled compound was obtained as a colourless solid (95.3 mg,
76%), mp 96–98 ꢂC. nmax (neat): 3417bm, 2926s, 2854s, 1717s, 1647s,
1559m, 1517m, 1450m, 1419w, 1339m, 1247m, 1105w, 1051w,
758m, 738m. 1H nmr (400 MHz, CDCl3): d 0.88 (3H, t, J=6.8Hz, H11),
1.26–1.32 (14H, m, H4–10), 1.61–1.91 (2H, m, H3), 4.23 (1H, t,
J=6.8Hz, H2), 4.40–4.47 (3H, m, CH & CH2), 5.25 (1H, d, J=8.0Hz,
NH), 7.31 (t, J= 7.4 Hz, 2H, H20 & H70), 7.40 (t, J= 7.4 Hz, 2H, H30 &
H60), 7.59–7.60 (m, 2H, H10 & H80), 7.76 (d, J= 7.4 Hz, 2H, H40 & H50),
OH not observed. 13C nmr (100 MHz, CDCl3): d 14.2 (C12), 22.8, 25.4,
29.3, 29.4, 29.5, 29.6, 32.0, 32.5, 47.3, 53.9, 67.2, 120.1, 125.2, 127.2,
127.9, 141.5, 143.9 & 144.0 (C80a & C90a), 156.2 (OCONH), 177.4 (C1).
LC-MS: 26 tR =5.47min (>98% pure), (ESI+, MeOH): m/z 446.1
(M + Na)+, C26H33NO4Na requires 446.23.
Compound 23
The reaction was also performed on larger scale, following the
general procedure previously described. N-Fmoc allylglycine
(1.00 g, 2.96 mmol), degassed DCM (30 ml), 1-octene (2.32 ml,
14.8 mmol, 5 eq.) and HGII (46.5 mg, 2.5 mol%) were used. After
purification, the titled compound was obtained (0.89 g, 71%).
Spectroscopic data were consistent with previously described
data for 26.
The titled compound was obtained as a colourless solid (73.4 mg,
65%), mp 123–124 ꢂC. nmax (neat): 3374m, 2923s, 2856s, 1754s,
1739m, 1675s, 1558s, 1456s, 1377m, 1266m, 1165m, 1125m,
1088w, 1046w, 741m, 734m cmꢀ1 1H nmr (400 MHz, CDCl3):
.
d 0.88 (3H, t, J = 6.8 Hz, H8), 1.29–1.43 (8H, m, H4–7), 1.66–1.94
(2H, m, H3), 4.23 (1H, t, J = 6.8 Hz, H2), 4.38–4.45 (1H, m, CH),
4.42 (2H, d, J = 6.8 Hz, CH2), 5.26 (1H, d, J = 8.0 Hz, NH), 7.31
(t, J = 7.4 Hz, 2H, H20 & H70), 7.40 (t, J = 7.4 Hz, 2H, H30 & H60),
7.58–7.61 (m, 2H, H10 & H80), 7.76 (d, J = 7.4 Hz, 2H, H40 & H50),
OH not observed. 13C nmr (100 MHz, CDCl3): d 14.2 (C8), 22.7,
25.3, 28.9, 31.7, 32.5, 47.3, 54.0, 67.2, 120.1, 125.2, 127.2, 127.9,
141.5, 143.9 & 144.0 (C80a & C90a), 156.2 (OCONH), 177.4 (C1).
LC-MS: 23 tR = 5.23 min (>98% pure), (ESI+, MeOH): m/z 404.1
(M + Na)+, C23H27NO4Na requires 404.18.
Compound 27
The titled compound was obtained as a colourless solid (103.6 mg,
80%), mp 61–62 ꢂC. nmax (neat): 3334bm, 2924s, 2853s, 1715s,
1635m, 1521m, 1465m, 1450s, 1419m, 1339m, 1247m, 1117w,
1079m, 1052m, 758m, 738m. 1H nmr (400MHz, CDCl3): d 0.88 (3H, t,
J=6.8Hz, H12), 1.26–1.37 (16H, m, H4–11), 1.64–1.93 (2H, m, H3),
4.22 (1H, t, J=6.8Hz, H2), 4.37–4.48 (1H, m, CH), 4.41 (2H, d,
J=6.8Hz, CH2), 5.31 (1H, d, J= 8.0 Hz, NH), 7.30 (t, J= 7.4 Hz, 2H, H20
& H70), 7.39 (t, J= 7.4 Hz, 2H, H30 & H60), 7.57–7.60 (m, 2H, H10 & H80),
7.75 (d, J= 7.4 Hz, 2H, H40 & H50), OH not observed. 13C nmr
(100 MHz, CDCl3): d 14.2 (C12), 22.8, 25.4, 29.3, 29.46, 29.54, 29.71,
29.72, 32.0, 32.5, 47.3, 54.1, 67.2, 120.1, 125.2, 127.2, 127.9, 141.5,
143.8 & 144.0 (C80a & C90a), 156.3 (OCONH), 177.6 (C1). LC-MS: 27 tR =
5.45 min (>98% pure), (ESI+, MeOH): m/z 460.2 (M + Na)+,
C27H35NO4Na requires 460.25.
Compound 24
The titled compound was obtained as a colourless solid (94.8 mg,
81%), mp 112–114 ꢂC. nmax (neat): 3323bm, 2928s, 2856s, 1716s,
1635m, 1519s, 1450s, 1418m, 1338m, 1264m, 1115w, 1078m,
1050m, 758m, 739s. 1H nmr (400 MHz, CDCl3): d 0.88 (3H, t,
J = 6.8 Hz, H9), 1.26–1.42 (10H, m, H4–8), 1.64–1.94 (2H, m, H3),
4.22 (1H, t, J = 6.8 Hz, H2), 4.38–4.45 (1H, m, CH), 4.41 (2H, d,
J = 7.2 Hz, CH2), 5.26 (1H, d, J = 8.0 Hz, NH), 7.30 (t, J = 7.4 Hz, 2H,
H20 & H70), 7.39 (t, J = 7.4 Hz, 2H, H30 & H60), 7.57–7.60 (m, 2H,
H10 & H80), 7.75 (d, J = 7.4 Hz, 2H, H40 & H50), OH not observed.
13C nmr (100 MHz, CDCl3): d 14.2 (C9), 22.7, 25.4, 29.2, 29.3, 31.9,
32.5, 47.3, 54.0, 67.2, 120.1, 125.2, 127.2, 127.9, 141.5, 143.9 &
144.0 (C80a & C90a), 156.3 (OCONH), 177.2 (C1). LC-MS: 24 tR = 5.49
min (>98% pure), (ESI+, MeOH): m/z 418.1 (M + Na)+,
C24H29NO4Na requires 418.20.
Compound 28
The title compound was obtained as a colourless solid (100.2 mg,
75%), mp 95–96 ꢂC. nmax (neat): 3339m, 3065m, 2925s, 2852s,
1718s, 1696s, 1539m, 1517m, 1465m, 1450m, 1419w, 1340m,
1247m, 1079w, 1052w, 758m, 739 s. 1H nmr (400 MHz, CDCl3):
d 0.89 (3H, t, J= 6.8Hz, H13), 1.26–1.37 (18H, m, H4–12), 1.62–1.93
(2H, m, H3), 4.22 (1H, t, J = 6.8 Hz, H2), 4.38–4.48 (1H, m, CH), 4.41
(2H, d, J = 6.8 Hz, CH2), 5.30 (1H, d, J = 8.0 Hz, NH), 7.30 (t, J = 7.4 Hz,
2H, H20 & H70), 7.39 (t, J= 7.4Hz, 2H, H30 & H60), 7.58–7.61 (m, 2H,
H10 & H80), 7.76 (d, J = 7.4Hz, 2H, H40 & H50), OH not observed.
13C nmr (100 MHz, CDCl3): d 14.2 (C13), 22.8, 25.4, 29.3, 29.49,
29.54, 29.71, 29.75, 29.76, 32.1, 32.5, 47.3, 54.0, 67.2, 120.1, 125.2,
127.2, 127.9, 141.5, 143.8 & 144.0 (C80a & C90a), 156.3 (OCONH),
Compound 25
The titled compound was obtained as a colourless solid (88.5 mg,
73%), mp 65–67 ꢂC. nmax (neat): 3431bm, 3065m, 2925s, 2854s,
1718s, 1696s, 1539m, 1517m, 1450s, 1419w, 1340m, 1248m,
1115w, 1052m, 758m, 738s. 1H nmr (400 MHz, CDCl3): d 0.88
(3H, t, J = 6.8 Hz, H10), 1.26–1.37 (12H, m, H4–9), 1.64–1.93
J. Pept. Sci. 2013
Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.
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