Journal of Medicinal Chemistry
Article
71.5, 54.1, 31.2, 28.2, 27.6, 22.4, 18.9, 14.2, 9.0. HRMS (ESI-TOF)
calculated for C12H20O3Na [M + Na]+, 235.1310; observed, 235.1310.
(E)-Oct-3-en-1-yl 2-Hydroxybutanoate, 29. 29 was prepared
according to method B, using (E)-3-octen-1-ol to provide (E)-oct-3-
en-1-yl 2-hydroxybutanoate (88 mg, 98% yield). 1H NMR (500 MHz,
CDCl3) δ 5.54−5.44 (m, 1H), 5.36−5.26 (m, 1H), 4.23−4.07 (m,
3H), 2.79 (s, 1H), 2.32 (q, J = 6.7 Hz, 2H), 2.00−1.90 (m, 2H), 1.84−
1.74 (m, 1H), 1.70−1.58 (m, 1H), 1.34−1.19 (m, 4H), 0.93 (t, J = 7.4
Hz, 3H), 0.85 (t, J = 7.0 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ
175.5, 134.2, 124.7, 71.5, 65.4, 32.5, 32.1, 31.7, 27.7, 22.3, 14.1, 9.1.
HRMS (ESI-TOF) calculated for C12H22O3Na [M + Na]+, 237.1466;
observed, 237.1475.
(Z)-Oct-3-en-1-yl 2-Hydroxybutanoate, 30. 30 was prepared
according to method B, using (Z)-3-octen-1-ol to provide (Z)-oct-3-
en-1-yl 2-hydroxybutanoate (60 mg, 30% yield). 1H NMR (500 MHz,
CDCl3) δ 5.55−5.43 (m, 1H), 5.34−5.23 (m, 1H), 4.21−4.08 (m,
3H), 2.79 (d, J = 3.4 Hz, 1H), 2.38 (q, J = 7.0 Hz, 2H), 2.08−1.95 (m,
1H), 1.84−1.74 (m, 1H), 1.69−1.59 (m, 1H), 1.34−1.24 (m, 4H),
0.93 (t, J = 7.5 Hz, 3H), 0.87 (t, J = 7.0 Hz, 3H). 13C NMR (126 MHz,
CDCl3) δ 175.5, 133.5, 123.9, 71.6, 65.2, 31.9, 27.7, 27.2, 27.0, 22.5,
14.1, 9.1. HRMS (ESI-TOF) calculated for C12H22O3Na [M + Na]+,
237.1466; observed, 237.1475.
Oct-3-yn-1-yl 2-Hydroxybutanoate, 31. 31 was prepared
according to method B, using 3-octyn-1-ol to provide oct-3-yn-1-yl
2-hydroxybutanoate (110 mg, 52% yield). 1H NMR (500 MHz,
CDCl3) δ 4.29−4.13 (m, 3H), 2.70 (s, 1H), 2.54−2.46 (m, 2H) 2.14−
2.07 (m, 2H), 1.88−1.77 (m, 1H), 1.74−1.62 (m, 1H), 1.47−1.31 (m,
4H), 0.95 (t, J = 7.4 Hz, 3H), 0.88 (t, J = 7.2 Hz, 3H). 13C NMR (126
MHz, CDCl3) δ 175.3, 82.5, 75.2, 71.5, 64.1, 31.1, 27.7, 22.1, 19.5,
18.5, 13.8, 9.1. HRMS (ESI-TOF) calculated for C12H20O3Na [M +
Na]+, 235.1310; observed, 235.1313.
(2-Pentylcyclopropyl)methyl 2-Hydroxybutanoate, 36. 36
was prepared according to method B, using (2-pentylcyclopropyl)-
methanol to provide (2-pentylcyclopropyl)methyl 2-hydroxybutanoate
1
as a mixture of stereoisomers (23.7 mg, 60% yield). H NMR (500
MHz, CDCl3) δ 4.17−4.11 (m, 1H), 4.10−3.90 (m, 2H), 2.76 (d, J =
5.6 Hz, 1H), 1.89−1.78 (m, 1H), 1.73−1.62 (m, 1H), 1.39−1.20 (m,
7H), 1.18−1.08 (m, 1H), 0.95 (t, J = 7.4 Hz, 3H), 0.86 (t, J = 6.9 Hz,
3H), 0.70−0.61 (m, 1H), 0.45−0.38 (m, 1H), 0.38−0.31 (m, 1H). 13C
NMR (126 MHz, CDCl3) δ 175.63, 71.6, 71.5, 70.4, 70.3, 33.6, 31.8,
29.3, 29.3, 27.7, 22.9, 18.1, 18.0, 17.3, 17.3, 14.3, 10.7, 10.7, 9.1, 9.1.
HRMS (ESI-TOF) calculated for C13H25O3 [M + H]+, 229.1804;
observed, 229.1810.
4-Phenylbutyl 2-Hydroxybutyrate, 37. 37 was prepared
according to method B, using 4-phenyl-1-butanol to provide 4-
1
phenylbutyl 2-hydroxybutyrate (200 mg, 85% yield). H NMR (500
MHz, CDCl3) δ 7.30−7.22 (m, 2H), 7.21−7.13 (m, 3H), 4.25−4.14
(m, 2H), 4.13 (dd, J = 6.6, 4.4 Hz, 1H), 2.70 (s, 1H), 2.67−2.57 (m,
2H), 1.87−1.76 (m, 1H), 1.73−1.61 (m, 5H), 0.94 (t, J = 7.4 Hz, 3H).
13C NMR (126 MHz, CDCl3) δ 175.4, 141.8, 128.4, 128.4 125.9, 71.4,
65.5, 35.4, 28.2, 27.6, 27.5, 8.9. HRMS (ESI-TOF) calculated for
C14H21O3 [M + H]+, 237.1491; observed, 237.1494.
5-Phenylpentyl 2-Hydroxybutyrate, 38. 38 was prepared
according to method B, using 5-phenylpentan-1-ol to provide 5-
1
phenylpentyl 2-hydroxybutyrate (220 mg, 88% yield). H NMR (500
MHz, CDCl3) δ 7.29−7.11 (m, 2H), 7.19−7.12 (m, 3H), 4.22−4.07
(m, 3H), 2.71 (d, J = 5.7 Hz, 1H), 2.60 (t, J = 7.7 Hz, 2H), 1.84−1.76
(m, 1H), 1.71−1.58 (m, 5H), 1.43−1.33 (m, 2H), 0.93 (t, J = 7.4 Hz,
3H). 13C NMR (126 MHz, CDCl3) δ 175.6, 142.4, 128.6, 128.5, 126.0,
71.5, 65.8, 35.9, 31.2, 28.6, 27.7, 25.6, 9.1. HRMS (ESI-TOF)
calculated for C15H23O3 [M + H]+, 251.1647; observed, 251.1655.
3-Cyclohexylpropyl 2-Hydroxybutyrate, 39. 39 was prepared
according to method B, using 3-cyclohexyl-1-propanol to provide 3-
(E)-Oct-4-enyl 2-Hydroxybutanoate, 32. 32 was prepared
1
cyclohexylpropyl 2-hydroxybutyrate (218 mg, 96% yield). H NMR
according to method B, using (E)-4-octyn-1-ol to provide (E)-oct-4-
(500 MHz, CDCl3) δ 4.21−4.08 (m, 3H), 2.72 (s, 1H), 1.87−1.77 (m,
1H), 1.73−1.58 (m, 8H), 1.25−1.05 (m, 6H), 0.94 (t, J = 7.4 Hz, 3H),
0.90−0.78 (m, 2H). 13C NMR (126 MHz, CDCl3) δ 175.6, 71.6, 66.3,
37.5, 33.6, 33.5, 27.7, 26.8, 26.5, 26.2, 9.1. HRMS (ESI-TOF)
calculated for C13H25O3 [M + H]+, 229.1804; observed, 229.1809.
4-Cyclohexylbutyl 2-Hydroxybutyrate, 40. 40 was prepared
according to method B, using 4-cyclohexyl-1-butanol to provide 4-
cyclohexylbutyl 2-hydroxybutyrate (225 mg, 93% yield). 1H NMR
(500 MHz, CDCl3) δ 4.22−4.09 (m, 3H), 2.78 (s, 1H), 1.87−1.76 (m,
1H), 1.70−1.56 (m, 8H), 1.37−1.28 (m, 2H), 1.24−1.03 (m, 6H),
0.94 (t, J = 7.4 Hz, 3H), 0.89−0.76 (m, 2H). 13C NMR (126 MHz,
CDCl3) δ 175.6, 71.5, 66.0, 37.7, 37.2, 33.5, 29.0, 27.7, 26.9, 26.6, 23.2,
9.1. HRMS (ESI-TOF) calculated for C14H27O3 [M + H]+, 243.1960;
observed, 243.1962.
1
enyl 2-hydroxybutanoate (69.9 mg, 75% yield). H NMR (500 MHz,
CDCl3) δ 5.46−5.29 (m, 2H), 4.22−4.09 (m, 3H), 2.75 (s, 1H), 2.04
(q, J = 7.0 Hz, 2H), 1.93 (q, J = 6.9 Hz, 2H), 1.87−1.77 (m, 1H),
1.74−1.62 (m, 3H), 1.39−1.29 (m, 2H), 0.94 (t, J = 7.4 Hz, 3H), 0.86
(t, J = 7.4 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 175.6, 131.9,
128.7, 71.5, 65.3, 34.8, 28.9, 28.6, 27.7, 22.8, 13.9, 9.1. HRMS (ESI-
TOF) calculated for C12H23O3 [M + H]+, 215.1647; observed,
215.1644.
(Z)-Oct-4-enyl 2-Hydroxybutanoate, 33. 33 was prepared
according to method B, using (Z)-4-octyn-1-ol to provide (Z)-oct-4-
1
enyl 2-hydroxybutanoate (42.7 mg, 55% yield). H NMR (500 MHz,
CDCl3) δ 5.45−5.27 (m, 2H), 4.23−4.09 (m, 3H), 2.76 (d, J = 5.7 Hz,
1H), 2.09 (q, J = 7.3 Hz, 2H), 1.97 (q, J = 7.3 Hz, 2H), 1.88−1.77 (m,
1H), 1.76−1.62 (m, 3H), 1.39−1.28 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H),
0.87 (t, J = 7.2 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 175.5, 131.4,
128.2, 71.5, 65.4, 29.5, 28.7, 27.7, 23.6, 23.0, 14.0, 9.1. HRMS (ESI-
TOF) calculated for C12H23O3 [M + H]+, 215.1647; observed,
215.1646.
5-Cyclohexylpentyl 2-Hydroxybutyrate, 41. 41 was prepared
according to method B, using 5-cyclohexyl-1-butanol to provide 5-
1
cyclohexylpentyl 2-hydroxybutyrate (151 mg, 59% yield). H NMR
(500 MHz, CDCl3) δ 4.21−4.10 (m, 3H), 2.73 (d, J = 5.7 Hz, 1H),
1.87−1.76 (m, 1H), 1.70−1.57 (m, 8H), 1.35−1.25 (m, 4H), 1.23−
1.06 (m, 6H), 0.94 (t, J = 7.4 Hz, 3H), 0.88−0.76 (m, 2H). 13C NMR
(126 MHz, CDCl3) δ 175.6, 71.5, 66.0, 37.8, 37.5, 33.6, 28.8, 27.7,
26.9, 26.6, 26.6, 26.3, 9.1. HRMS (ESI-TOF) calculated for C15H29O3
[M + H]+, 257.2117; observed, 257.2120.
(E)-Oct-5-enyl 2-Hydroxybutanoate, 34. 34 was prepared
according to method B, using (E)-5-octyn-1-ol to provide (E)-oct-5-
1
enyl 2-hydroxybutanoate (41.3 mg, 65% yield). H NMR (500 MHz,
CDCl3) δ 5.49−5.29 (m, 2H), 4.23−4.09 (m, 3H), 2.74 (d, J = 5.7 Hz,
1H), 2.04−1.93 (m, 4H), 1.86−1.78 (m, 1H), 1.71−1.59 (m, 3H),
1.44−1.35 (m, 2H), 0.94 (t, J = 7.4 Hz, 6H). 13C NMR (125 MHz,
CDCl3) δ 175.6, 133.0, 128.5, 71.5, 65.8, 32.2, 28.2, 27.7, 25.9, 25.8,
14.2, 9.1. HRMS (ESI-TOF) calculated for C12H23O3 [M + H]+,
215.1647; observed, 215.1642.
(Z)-Oct-5-en-1-yl 2-Hydroxybutanoate, 35. 35 was prepared
according to method B, using (Z)-5-octen-1-ol to provide (Z)-oct-5-
en-1-yl 2-hydroxybutanoate (116 mg, 78% yield). 1H NMR (500
MHz, CDCl3) δ 5.42−5.34 (m, 1H), 5.32−5.23 (m, 1H), 4.23−4.09
(m, 3H), 2.09−1.96 (m, 4H), 1.86−1.77 (m, 1H), 1.70−1.61 (m, 3H),
1.45−1.35 (m, 2H), 0.99−0.88 (m, 6H). 13C NMR (126 MHz,
CDCl3) δ 175.6, 132.6, 128.4, 71.5, 65.8, 28.3, 27.7, 26.7, 26.1, 20.7,
14.6, 9.1. HRMS (ESI-TOF) calculated for C12H22O3Na [M + Na]+,
237.1466; observed, 237.1472.
1-(p-Butylphenyl)methyl 2-Hydroxybutyrate, 42. 42 was
prepared according to method B, using (4-butylphenyl)methanol to
provide 1-(p-butylphenyl)methyl 2-hydroxybutyrate (193 mg, 74%
1
yield). H NMR (500 MHz, CDCl3) δ 7.25 (d, J = 7.1 Hz, 2H), 7.17
(d, J = 8.0 Hz, 2H), 5.16 (s, 2H), 4.17 (dd, J = 6.7, 4.3 Hz, 1H), 2.59
(dd, J = 7.8, 7.8 Hz, 2H), 1.88−1.78 (m, 1H), 1.72−1.62 (m, 1H),
1.61−1.52 (m, 2H), 1.38−1.28 (m, 2H), 0.91 (t, J = 7.4 Hz, 3H), 0.90
(t, J = 7.3 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 175.4, 143.7,
132.5, 128.9, 128.7, 71.6, 67.6, 35.6, 33.8, 27.7, 22.5, 14.2, 9.1. HRMS
(ESI-TOF) calculated for C15H22O3Na [M + Na]+, 237.1466;
observed, 273.14715.
1-(m-Butylphenyl)methyl 2-Hydroxybutyrate, 43. 43 was
prepared according to method B, using (3-butylphenyl)methanol to
provide 1-(m-butylphenyl)methyl 2-hydroxybutyrate (29 mg, 47%
9679
dx.doi.org/10.1021/jm300908t | J. Med. Chem. 2012, 55, 9669−9681