SYNTHESIS OF 2-AMINO-4-METHYLDECANOIC ACIDS
The reaction mixture was stirred at that temperature for 20 min
and then (E)-1-iodohex-2-ene (3.15 g, 15.0 mmol) was added via
a syringe. After being stirred for 8 h at −78 ◦C, the reaction
was quenched by addition of saturated aqueous NH4Cl solution.
The mixture was warmed to room temperature; diluted with Et2O
(200 mL); washed with 10% Na2S2O3 and brine; dried over Na2SO4;
and concentrated in vacuo. The residue was purified by flash
column chromatography, eluting with EtOAc/petroleum ether
(1 : 5 → 1 : 3) to give compound 4 (2.33 g, 91%) as a colorless oil.
(brs, 15H, Boc+(CH3)2), 1.55–1.72 (brm, 3H), 1.89–2.13 (brm,
4H, CH2CH CHCH2), 3.34–4.04 (brm, overlapped, 5H), 5.33–5.50
(m, 2H, CH CH); HRESIMS calculated for C19H35NO4Na 364.2458
[M+Na]+, found 364.2432.
Compound 7
Triethylamine (4.2 mL, 30 mmol) was added to a solution of 5
in dichloromethane at 0 ◦C. TsCl (3.81 g, 20 mmol) and DMAP
(244 mg, 2 mmol) were then added at the same temperature and
stirred overnight. The mixture was diluted with dichloromethane
and then washed with 1 M HCl, H2O, saturated aqueous NaHCO3,
and brine, dried over Na2SO4 and concentrated in vacuo. The
residue was purified by flash silica gel chromatography, eluting
with EtOAc/petroleum ether to give compound 6 as a colorless oil
(4.81 g, 97%).
25
1
[α]D = −11.4 (c = 1.4, MeOH); H NMR (CDCl3, 600 MHz) δ
0.88(tlike,J = 6.9 Hz,3H,CH3CH2),1.34–1.38(m,2H,CH3CH2CH2),
1.42 (s, 9H, Boc), 1.45 (s, 3H), 1.51 (s, 3H), 1.74–1.78 (m, 1H),
1.95–1.98 (m, 3H), 2.18–2.23 (m, 1H), 2.44–2.46 (m, 1H), 2.73–2.77
(m, 1H, PhCHaHb), 3.25–3.27 (m, 1H, PhCHaHb), 3.56–3.57 (m, 1H),
3.65–3.67 (m, 1H), 3.90–3.92 (m, 1H), 4.04–4.06 (m, 1H), 4.11–4.13
(m, 1H), 4.25–4.28 (m, 1H), 4.77–4.79 (m, 1H), 5.39–5.43 (m, 1H),
5.46–5.50 (m, 1H), 7.23–7.27 (m, 3H), 7.31–7.34 (m, 2H); 13C NMR
(CDCl3, 150 MHz) δ 13.7, 22.5, 24.4, 28.1, 28.4, 29.4, 29.7, 34.6,
35.6, 35.9, 38.7, 39.9, 54.8, 55.4, 66.3, 68.5, 80.1, 93.6, 126.3, 127.1,
128.8, 129.4, 133.5, 135.8, 153.3, 175.3; HRESIMS calculated for
C29H42N2O6Na 537.2935 [M+Na]+, found 537.2888.
LiAlH4 (1.10 g, 29 mmol) was added in small portions to a
solutionoftosylate6(4.81 g,9.7 mmol)inEt2Oat0 ◦C.Thereaction
mixture was stirred for 3 h at room temperature, quenched by
dropwise addition of water (1 mL), 15% aqueous NaOH (1 mL), and
water (3 mL). The mixture was stirred for 1 h at room temperature,
and then MgSO4 (5 g) was added. The suspension was filtered
through a pad of celite, washed with Et2O, and concentrated in
vacuo. The residue was purified by flash silica gel chromatography,
eluting with EtOAc/petroleum ether to give compound 7 as a
colorless oil (2.65 g, 84%).
Compound 4a
Prepared as described above for 4.
Yield 96%. Colorless oil. [α]D = 283.6 (c = 0.4, MeOH). 1H
26
NMR (CDCl3, 600 MHz) δ 0.87 (t, J = 7.3 Hz, 3H, CH3CH2), 1.35
(sex., J = 7.3 Hz, 2H, CH3CH2CH2), 1.45 (s, 3H), 1.49 (s, 9H, Boc),
1.60 (s, 3H), 1.72–1.77 and 2.15 (two brm, 2H), 1.94–1.97 (brm,
2H, CH2CH CH), 2.25–2.45 (brm, 2H, CH CHCH2), 2.60–2.70 (m,
1H, PhCHaHb), 3.31 (dd, J = 13.3, 2.7 Hz, 1H, PhCHaHb), 3.68–3.89
(brm, 3H), 4.10–4.18 (brm, 2H, Oxa H-3), 4.66–4.75 (brm, 1H, Oxa
H-4), 5.38–5.41 (m, 1H, CH CH), 5.50–5.51 (m, 1H, CH CH),
7.21–7.34 (m, 5H, Ar H); HRESIMS calculated for C29H42N2O6Na
537.2935 [M+Na]+, found 537.2890.
25
[α]D = 36.2 (c = 0.5, MeOH). 1H NMR (CDCl3, 600 MHz) δ
0.86–0.92 (t and d, overlapped, 6H), 1.32–1.40 (brm, overlapped,
3H), 1.48–1.81(brm, 17H), 1.96–2.17 (brm, 4H), 3.72–4.01 (brm,
overlapped, 3H), 5.33–5.42 (brm, 2H, CH CH); 13C NMR (CDCl3,
150 MHz) δ 13.7, 22.7, 23.3, 27.0, 28.6, 29.4, 34.7, 39.3, 41.2,
56.0, 67.7, 79.8, 93.6, 128.5, 132.2, 152.4; HRESIMS calculated
for C19H35NO3Na 348.2509 [M+Na]+, found 348.2511.
Compound 7a
Compound 5
Prepared as described above for 7.
26
Yield 87%. Colorless oil. [α]D = 67.2 (c = 1.2, MeOH). 1H
LiAlH4 (1.14 g, 30 mmol) was added in small portions to a solution
of oxazolidinone 4 (5.15 g, 10 mmol) in Et2O at 0 ◦C. The reaction
mixture was stirred for 3 h at room temperature, quenched by
dropwise addition of water (1 mL), 15% aqueous NaOH (1 mL), and
water (3 mL). The mixture was stirred for 1 h at room temperature,
and then MgSO4 (5 g) was added. The suspension was filtered
through a pad of celite, washed with Et2O and concentrated in
vacuo. The residue was purified by flash silica gel chromatography,
eluting with EtOAc/petroleum (2 : 1) ether to give alcohol 5 as a
colorless oil (2.85 g, 84%).
NMR (CDCl3, 600 MHz) δ 0.89 (t, J = 7.3 Hz, 3H, CH2CH3), 0.90 (d,
overlapped, 3H, CHCH3), 1.35–1.40 (brm, 3H), 1.47 and 1.59 (brs,
15H, Boc+(CH3)2), 1.87–2.01 (brm, 4H), 3.71 (t, J = 8.2 Hz, 1H),
3.84 and 3.99 (brm, 1H), 3.90 (dd, J = 8.2, 5.9 Hz, 1H), 5.32–5.45
(m, 2H, CH CH); HRESIMS calculated for C19H35NO3Na 348.2509
[M+Na]+, found 348.2504.
Compound 8
1HNMR(CDCl3, 600 MHz)δ 0.88(t, J = 7.5 Hz, 3H), 1.35–1.38(m,
2H), 1.49 (brs 12H), 1.55 (s, 3H), 1.60–1.69 (brm, 3H), 1.84–1.99 (m,
4H), 3.47–4.22 (brm overlapped, 5H), 5.33–5.37 (m, 1H), 5.41–5.49
(m, 1H); 13C NMR (CDCl3, 150 MHz) δ 13.7, 22.6, 24.5, 28.4, 28.6,
29.4, 34.6, 36.3, 37.9, 55.2, 66.6, 68.4, 80.5, 93.3, 127.9, 132.5, 152.7;
HRESIMS calculated for C19H35NO4Na 364.2458 [M+Na]+, found
364.2449.
Palladium on charcoal (65 mg, 10% weight) was added to a
solution of compound 7 (651 mg, 2 mmol) in EtOAc (10 mL).
The reaction mixture was purged with hydrogen three times and
stirred for 2 h at room temperature. The suspension was filtered
through a pad of celite, washed with EtOAc (3 × 5 mL), and
concentrated in vacuo, to give compound 8 as a colorless oil
(629 mg, 96%).
26
[α]D = 24.9 (c = 1.3, MeOH). 1H NMR (CDCl3, 600 MHz,
mixture of rotamers) δ 0.88 (t, J = 6.6 Hz, 3H, CH3CH2), 0.90 (d,
J = 6.6 Hz, 3H, CH3CH), 1.06–1.73 (brm, total 28H), 3.73 (brd,
J = 8.4 Hz, 1H), 3.83 and 3.99 (brm, total 1H), 3.91–3.93 (m, 1H);
13C NMR (CDCl3, 150 MHz) δ 14.1, 20.8, 22.7, 28.6, 29.6, 30.8, 31.9,
36.1, 41.6, 56.0, 67.6, 79.8, 93.5, 151.7; HRESIMS calculated for
C19H37NO3Na 350.2666 [M+Na]+, found 350.2659.
Compound 5a
Prepared as described above for 5.
26
Yield 90%. Colorless oil. [α]D = 88.2 (c = 0.4, MeOH); 1H
NMR (CDCl3, 600 MHz, mixture of rotamers) δ 0.88 (t, J = 7.3 Hz,
3H, CH3CH2), 1.37 (sex., J = 7.2 Hz, 2H, CH3CH2CH2), 1.44, 1.48
c
J. Pept. Sci. 2011; 17: 576–580 Copyright ꢀ 2011 European Peptide Society and John Wiley & Sons, Ltd. wileyonlinelibrary.com/journal/jpepsci