4.1.2.5.isobutyl((2R,3S)-3-((S)-sec-butyl)-4-oxooxetane-2-
1H NMR (400 MHz, CDCl3): δ 6.87 (d, J = 8.5 Hz, 1H), 6.18 (d,
J = 8.4 Hz, 1H), 4.86 (d, J = 4.6 Hz, 1H), 4.55 (dd, J = 8.8, 4.7
Hz, 1H), 4.28 (dd, J = 8.4, 6.6 Hz, 1H), 3.75 (s, 3H), 3.66 (dd, J
= 7.7, 4.6 Hz, 1H), 2.23-2.13 (m, 2H), 2.05-1.96 (m, 1H), 1.69-
1.60 (m, 1H), 1.37- 1.27 (m, 1H), 1.08 (d, J = 6.7 Hz, 3H), 1.00-
0.89 (m, 15H); 13C NMR (100 MHz, CDCl3): δ 172.1, 169.9,
168.7, 168.1, 70.5, 82.9, 58.6, 57.1, 52.3, 33.7, 31.1, 30.9, 26.7,
19.1, 18.9, 18.1, 17.7, 16.3, 11.0; HRMS (ESI+) m/z: [M+H]+
Calc’d for C19H33N2O6 385.2333; Found 385.2347.
ACCEPTED MANUSCRIPT
carbonyl)-L-valyl-L-valinate (3d): White amorphous solid; Yield:
70%; Rf : 0.5 (Hexanes: EtOAc = 5:1); [α]ꢁꢀꢄ = - 2.8 (c 0.25,
1
CHCl3); IR (γ, cm-1): 3290, 2351, 1843, 1645, 1557; H NMR
(400 MHz, CDCl3): δ 6.96 (d, J = 8.5 Hz, 1H), 6.38 (d, J = 8.5
Hz, 1H), 4.66 (d, J = 4.77 Hz, 1H), 4.55 (dd, J = 4.8, 4.8 Hz, 1H),
4.29 (dd, J = 8.1, 6.9 Hz, 1H), 3.95 (m, 2H), 3.65 (dd, J = 7.6, 7.6
Hz, 1H), 2.23-2.11 (m, 2H), 2.01-1.88 (m, 3H), 1.67-1.59 (m,
1H), 1.34-1.23 (m, 2H), 1.06 (d, J = 6.8 Hz, 3H), 0.98 (m, 19H);
13C NMR (100 MHz, CDCl3): δ 171.7, 170.0, 168.8, 168.0, 71.5,
70.5, 62.8, 58.7, 57.1, 33.6, 31.2, 30.8, 27.6, 26.6, 19.1, 19.0,
18.9, 18.1, 17.6, 16.3, 10.9; HRMS (ESI+) m/z: [M+H]+ Calc’d
for C22H39N2O6 427.2803; Found 427.2823.
4.1.2.10.benzyl((2R,3S)-3-cyclopropyl-4-oxooxetane-2-
carbonyl)-L-valyl-L-valinate (4a): Pale yellow oil; Yield: 53%;
Rf : 0.5 (Hexanes: EtOAc = 2:1); [α]ꢁꢀꢅ = - 5.2 (c 0.23, CHCl3);
IR (γ, cm-1): 3270, 2360, 1843, 1740, 1646, 1558, 1457, 1205; 1H
NMR (400 MHz, CDCl3): δ 7.37-7.32 (m, 5H), 6.83 (d, J = 8.5
Hz, 1H), 6.2 (d, J = 8.4 Hz, 1H), 5.23-5.11 (m, 2H), 4.65 (d, J =
4.6 Hz, 1H), 4.59-4.55 (m, 1H), 4.26 (dd, J = 8.42, 8.25 Hz, 1H),
3.53 (dd, J = 4.9, 4.5 Hz, 1H), 2.22-2.11 (m, 2H), 1.25-1.20 (m,
2H), 0.97-0.84 (m, 12H), 0.74-0.65 (m, 2H), 0.54-0.51 (m, 1H),
0.46-0.42 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 171.5, 169.9,
167.8, 167.7, 135.1, 128.6, 128.5, 77.2, 67.3, 61.3, 58.7, 57.2,
31.1, 30.9, 19.1, 18.9, 18.1, 17.5, 8.6, 3.4, 2.9; HRMS (ESI+)
m/z: [M+H]+ Calc’d for C24H33N2O6 445.2333; Found 445.2323.
4.1.2.6.(2R,3S)-N-((S)-1-(((S)-1-(benzylamino)-3-methyl-1-
oxobutan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)-3-((S)-sec-
butyl)-4-oxooxetane-2-carboxamide (3e): White amorphous
solid; Yield: 52%; Rf : 0.3 (Hexanes: EtOAc = 2:1); [α]ꢁꢀꢁ = -
74.0 (c 0.25, MeOH); IR (γ, cm-1): 3269, 3085, 2324, 1842, 1635,
1
1551; H NMR (400 MHz, DMSO): δ 8.59 (d, J = 8.8 Hz, 1H),
8.53 (m, 1H), 8.08 (d, J = 8.7 Hz, 1H), 7.31-7.20 (m, 5H), 5.04
(d, J = 4.0 Hz, 1H), 4.36-4.30 (m, 2H), 4.26-4.13 (m, 2H), 3.66
(dd, J = 7.6, 7.6 Hz, 1H), 2.50 (m, 1H), 2.02-1.89 (m, 3H), 1.56-
1.45 (m, 1H), 1.29-1.20 (m, 1H), 0.95 (d, J = 6.7Hz, 3H), 0.86-
0.80 (m,15H); 13C NMR (100 MHz, DMSO): δ 170.8, 170.4,
167.4, 139.4, 128.2, 127.1, 126.7, 69.6, 61.1, 58.1, 57.6, 42.0,
32.6, 30.7, 30.4, 26.0, 19.2, 19.2, 18.4, 17.9, 15.8, 10.9; HRMS
analysis of 3e was not successful using ESI.
4.1.2.11. benzyl((2R,3S)-3-cyclobutyl-4-oxooxetane-2-carbonyl)-
L-valyl-L-valinate (4b): Pale yellow oil; Yield: 54%; Rf : 0.3
(Hexanes: EtOAc : 2 : 1); [α]ꢁꢀꢅ = - 8.0 (c 0.26, CHCl3); IR (γ,
1
cm-1): 3011, 2994, 2369, 1739, 1725, 1691; H NMR (400 MHz,
CHCl3): δ 7.39-7.32 (m, 5H), 6.86 (d, J = 8.3 Hz, 1H), 6.19 (d, J
= 8.7 Hz, 1H), 5.23 (d, J = 12.1 Hz, 1H), 5.14 (d, J = 12.2 Hz,
1H), 4.60 (d, J = 4.6 Hz, 2H), 4.27 (dd, J = 8.3, 6.8 Hz, 1H), 3.78
(dd, J = 7.0, 4.6 Hz, 1H), 2.90-2.81 (m, 1H), 2.24-2.09 (m, 4H),
2.06-1.89 (m, 4H), 0.97-0.94 (m, 6H), 0.92 (d, J = 6.7 Hz, 3H),
0.87 (d, J = 6.9 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 171.4,
170.0, 168.2, 168.0, 135.1, 128.6, 128.5, 128.4, 70.8, 67.2, 61.9,
58.7, 51.2, 32.8, 31.6, 31.1, 30.9, 25.2, 24.8, 22.6, 19.1, 18.9,
18.1, 18.1, 17.6; HRMS (ESI+) m/z: [M+H]+ Calc’d for
C25H35N2O6 459.2490; Found 459.2439.
4.1.2.7. 4-methoxybenzyl((2R,3S)-3-((S)-sec-butyl)-4-oxooxetane-
2-carbonyl)-L-valyl-L-valinate (3f): White amorphous solid;
Yield: 39%; Rf : 0.3 (Hexanes: EtOAc = 5:1); [α]ꢁꢀꢁ = - 11.2 (c
0.24, CHCl3); IR (γ, cm-1): 3278, 2964, 1837, 1739, 1646, 1614,
1
1515; H NMR (400 MHz, CDCl3): δ 7.31 (d, J = 9.0 Hz, 2H),
6.91 (d, J = 8.7 Hz, 2H), 6.33 (d, J = 8.9 Hz, 1H), 5.20 (d, J =
11.2 Hz, 1H), 5.08 (d, J = 11.6 Hz, 1H), 4.68 (d, J = 4.6 Hz, 1H),
4.58 (dd, J = 4.6, 4.6 Hz, 1H), 4.30 (dd, J = 8.3, 8.3 Hz, 1H),
3.83 (s, 3H), 3.67 (dd, J = 7.6, 7.6 Hz, 1H), 2.26-2.12 (m, 2H),
2.06-1.96 (m, 1H), 1.72-1.61 (m, 1H), 1.39-1.30 (m, 2H), 1.09 (d,
J = 6.8 Hz, 3H), 0.99 (m, 9H), 0.91 (d, J = 6.9 Hz, 3H), 0.86 (d, J
= 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 171.5, 170.0,
168.8, 168.1, 159.8, 130.3, 127.2, 113.9, 70.5, 67.0, 62.9, 58.7,
57.1, 55.3, 33.7, 31.1, 30.8, 26.7, 19.1, 18.9, 18.1, 17.5, 16.3,
11.0; HRMS (ESI+) m/z: [M+H]+ Calc’d for C26H39N2O7
491.2752; Found 491.2758.
4.1.2.12.benzyl((2R,3S)-3-cyclopentyl-4-oxooxetane-2-carbonyl)-
L-valyl-L-valinate (4c) Colorless oil; Yield: 67%; Rf : 0.6
(Hexanes: EtOAc = 3:1); [α]ꢁꢀꢁ = - 10.6 (c 0.4, CHCl3); IR (γ, cm-
1): 3175, 2323, 1642, 1599, 1471; 1H NMR (400 MHz, CDCl3): δ
7.38-7.31 (m, 5H), 6.91 (d, J = 8.3 Hz, 1H), 6.30 (d, J = 8.7 Hz,
1H), 5.23 (d, J = 11.9 Hz, 1H), 5.13 (d, J = 11.9 Hz, 1H), 4.61-
4.56 (m, 2H), 4.29 (dd, J = 8.4, 6.7 Hz, 1H), 3.67 (dd, J = 8.4, 4.5
Hz, 1H), 2.42-2.33 (m, 1H), 2.24-2.09 (m, 2H), 1.95-1.82 (m,
2H), 1.70-1.58 (m, 4H), 1.47-1.39 (m, 2H), 0.96 (dd, J = 6.5, 6.0
Hz, 6H), 0.91 (d, J = 6.9 Hz, 3H), 0.86 (d, J = 7.0 Hz, 3H); 13C
NMR (100 MHz, CDCl3): δ 171.5, 170.0, 168.8, 168.0, 135.1,
128.6, 128.5, 128.4, 71.8, 67.2, 62.0, 58.6, 57.1, 38.1, 31.1, 30.9,
29.9, 29.7, 25.1, 24.8, 19.1, 18.9, 18.1, 17.5; HRMS (ESI+) m/z:
[M+H]+ Calc’d for C26H37N2O6 473.2646; Found 473.2636.
4.1.2.8. but-3-en-1-yl((2R,3S)-3-((S)-sec-butyl)-4-oxooxetane-2-
carbonyl)-L-valyl-L-valinate (3g): Colorless amorphous solid;
Yield: 44%; Rf : 0.5 (Hexanes: EtOAc = 4:1); [α]ꢁꢀꢂ = - 5.8 (c 0.1,
CHCl3); IR (γ, cm-1): 3284, 2966, 1842, 1732, 1638, 1556, 1540;
1H NMR (400 MHz, CDCl3): δ 6.87 (d, J = 8.4 Hz, 1H), 6.17 (d,
J = 8.9 Hz, 1H), 5.81-5.71 (m, 1H), 5.14-5.08 (m, 2H), 4.66 (d, J
= 4.7 Hz, 1H), 4.55 (dd, J = 8.8, 4.5 Hz, 1H), 4.27-4.22 (m, 2H),
4.21-4.14 (m, 1H), 3.66 (dd, J = 7.5, 4.7 Hz, 1H), 2.43-2.38 (m,
2H), 2.23-2.14 (m, 2H), 2.04-1.96 (m, 1H), 1.70-1.62 (m, 1H),
1.38-1.27 (m, 1H), 1.08 (d, J = 6.6 Hz, 3H), 1.0-0.95 (m, 6H),
0.94-0.88 (m, 9H); 13C NMR (100 MHz, CDCl3): δ 171.6, 169.9,
168.8, 168.1, 133.5, 117.7, 70.5, 64.5, 62.9, 58.7, 57.1, 33.7,
33.0, 31.1, 30.9, 26.7, 19.2, 19.0, 18.1, 17.6, 16.3, 11.0; HRMS
(ESI+) m/z: [M+H]+ Calc’d for C22H37N2O6 425.2646; Found
425.2670.
4.1.2.13. benzyl ((2R,3S)-3-iso-butyl-4-oxooxetane-2-carbonyl)-
L-valyl-L-valinate (4d): White amorphous solid; Yield: 31%; Rf :
0.6 (Hexanes: EtOAc = 2:1); [α]ꢁꢀꢅ = -12.0 (c 0.1, CHCl3); IR (γ,
1
cm-1): 3027, 2353, 1744, 1739, 1764, 1454, 1376; H NMR (400
MHz, CDCl3): δ 7.37-7.35 (m, 5H), 6.87 (d, J = 8.8 Hz, 1H), 6.19
(d, J = 8.8 Hz, 1H), 5.23 (d, J =12.0 Hz, 1H), 5.14 (d, J = 12.2
Hz, 1H), 4.60-4.57 (m, 2H), 4.26 (m, 1H), 3.77-3.72 (m, 1H),
2.23-2.11 (m, 2H), 1.86-1.76 (m, 3H), 0.98 (m, 15H), 0.86 (d, J =
6.9 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 171.4, 170.0, 169.4,
167.8, 135.1, 128.6, 128.5, 128.4, 73.3, 67.2, 58.7, 57.1, 56.2,
37.1, 31.1, 30.8, 26.3, 22.4, 21.8, 19.1, 18.9, 18.1, 17.5; HRMS
4.1.2.9.methyl((2R,3S)-3-((S)-sec-butyl)-4-oxooxetane-2-
carbonyl)-L-valyl-L-valinate (3h): Colorless amorphous solid;
Yield: 43%; Rf : 0.3 (Hexanes: EtOAc = 4:1); [α]ꢁꢀꢄ = - 6.2 (c
0.003, CHCl3); IR (γ, cm-1): 2964, 1836, 1739, 1647, 1538, 1467;