Biomimetic Generation, Evaluation of Structure-Taste-Relationships and T1R1/T1R3-Receptor

Supporting information

Spectroscopic data of monohydroxyalkylamides (10-23):

N-Phenethyl-4-hydroxypentanamide 10:1H and 13C NMR data were well in agreement with those reported in [1]. UV/Vis (1% aq. HCOOH/methanol): λmax=204, 220, 260nm.LC-TOF-MS (ESI+): m/z 244.1360 ([M+Na]+, measured); m/z 244.1308 ([M+Na]+, calculated for C13H19NNaO2). 1H NMR (400MHz, DMSO-d6, COSY): δ [ppm] 1.02 [d, 3H, J = 6.1Hz, H-C(5)], 1.45-1.57 [m, 2H, H-C(3)], 2.02-2.16 [m, 2H,H-C(2)], 2.69 [t, 2H, J = 7.9Hz, H-C(3’)], 3.21-3.27 [m, 2H, H-C(2’)], 3.50-3.57 [m, 1H, H-C(4)], 4.31 [broad d, 1H, J = 4.7Hz, H-O(6)], 7.17-7.22 [m, 2H, H-C(5’), H-C(9’)], 7.19-7.23 [m, 1H, H-C(7’)], 7.29 [d, 2H, J = 8.4Hz, H-C(6’), H-C(8’)], 7.87 [broad t, 1H, J = 5.4Hz, H-N(1’)]. 13C NMR (100MHz, DMSO-d6, HMBC, HSQC): δ [ppm] 23.4 [CH3, C(5)], 31.9 [CH2, C(2)], 34.7 [CH2, C(3)], 35.1 [CH2, C(3’)], 40.1 [CH2, C(2’)], 65.3 [CH, C(4)], 125.9 [CH, C(7’)], 128.2 [CH, C(6’), C(8’)], 128.5 [CH, C(5’), C(9’)], 139.4 [C, C(4’)], 172.1 [C, C(1)].

N-Phenethyl-(4R)-hydroxypentanamide (4R)-10: UV/Vis (1% aq. HCOOH/ methanol): λmax=204, 220, 260nm.LC-TOF-MS (ESI+): m/z 244.1360 ([M+Na]+, measured); m/z 244.1308 ([M+Na]+, calculated for C13H19NNaO2). 1H NMR (400MHz, DMSO-d6, COSY): δ [ppm] 1.02 [d, 3H, J = 6.2Hz, H-C(5)], 1.43-1.57 [m, 2H, H-C(3)], 1.96-2.19 [m, 2H,H-C(2)], 2.71 [t, 2H, J = 7.4Hz, H-C(3’)], 3.18-3.27 [m, 2H, H-C(2’)], 3.47-3.58 [m, 1H, H-C(4)], 4.43 [broad d, 1H, J = 4.6Hz, H-O(6)], 7.17-7.22 [m, 2H, H-C(5’), H-C(9’)], 7.19-7.23 [m, 1H, H-C(7’)], 7.29 [d, 2H, J = 8.4Hz, H-C(6’), H-C(8’)], 7.87 [broad t, 1H, J = 5.2Hz, H-N(1’)]. 13C NMR (100MHz, DMSO-d6, HMBC, HSQC): δ [ppm] 23.3 [CH3, C(5)], 31.9 [CH2, C(2)], 34.7 [CH2, C(3)], 35.1 [CH2, C(3’)], 40.1 [CH2, C(2’)], 65.3 [CH, C(4)], 125.9 [CH, C(7’)], 128.2 [CH, C(6’), C(8’)], 128.5 [CH, C(5’), C(9’)], 139.4 [C, C(4’)], 172.1 [C, C(1)].

N-Phenethyl-4-hydroxybutanamide 11: UV/Vis (1% aq. HCOOH/methanol): λmax=204, 220, 260nm. LC-TOF-MS (ESI+): m/z 230.1153 ([M+Na]+, measured); m/z 230.1151 ([M+Na]+, calculated for C12H17NNaO2). 1H NMR (400MHz, DMSO-d6, COSY): δ[ppm] 1.57-1.66 [m, 2H, H-C(3)], 2.06 [t, 2H, J = 7.7Hz, H-C(2)], 2.71 [t, 2H, J = 7.4Hz, H-C(3’)], 3.21-3.28 [m, 2H, H-C(2’)], 3.31-3.38 [m, 2H, H-C(4)], 4.45 [t, 1H, J = 5.2Hz, H-O(5)], 7.15-7.22 [m, 3H, H-C(5’), H-C(7’), H-C(9’)], 7.28 [d, 2H, J = 8.4Hz, H-C(6’), H-C(8’)], 7.85 [t, 1H, J = 5.4Hz, H-N(1’)]. 13C NMR (100MHz, DMSO-d6, 135-DEPT, HMBC, HMQC): δ[ppm] 28.7 [CH2, C(3)], 32.2 [CH2, C(2)], 35.2 [CH2, C(3’)], 40.1 [CH2, C(2’)], 60.4 [CH2, C(4)], 126.0 [CH, C(7’)], 128.3 [CH, C(5’), C(9’)], 128.6 [CH, C(6’), C(8’)], 139.5 [C, C(4’)], 172.0 [C, C(1)].

N-Phenethyl-4-hydroxyhexanamide 12: UV/Vis (1% aq. HCOOH/methanol): λmax=212, 260nm.LC-TOF-MS (ESI+): m/z 236.1648 ([M+H]+, measured); m/z 236.1645 ([M+H]+, calculated for C14H22NO2). 1H NMR (400MHz, CDCl3, COSY): δ [ppm] 0.93 [t, 3H, J = 7.4Hz, H-C(6)], 1.42-1.52 [m, 2H, H-C(5)], 1.56-1.69 [m, 1H, H-C(3a)], 1.76-1.87 [m, 1H, H-C(3b)], 2.29 [dt, 2H, J = 1.8, 6.8Hz, H-C(2)], 2.68 [broad s, 1H, H-O(7)], 2.82 [t, 2H, J = 6.9Hz, H-C(3’)], 3.46-3.51 [m, 1H, H-C(4)], 3.52 [dd, 2H,J = 6.2, 6.9Hz, H-C(2’)], 5.67 [broad s, 1H, H-N(1’)], 7.20 [d, 2H, J = 7.6Hz, H-C(5’), H-C(9’)], 7.23 [d, 1H, J = 7.1Hz, H-C(7’)], 7.37 [dd, 2H, J = 7.1, 7.6Hz, H-C(6’), H-C(8’)]. 13C NMR (100MHz, CDCl3, 135-DEPT, HMBC, HMQC): δ [ppm] 10.0 [CH3, C(6)], 30.5 [CH2, C(5)], 32.0 [CH2, C(3)], 33.3 [CH2, C(2)], 35.6 [CH2, C(3’)], 40.6 [CH2, C(2’)], 72.8 [CH, C(4)], 126.6 [CH, C(7’)], 128.7 [CH, C(6’), C(8’)], 128.8 [CH, C(5’), C(9’)], 138.8 [C, C(4’)], 173.6 [C, C(1)].

N-Phenethyl-4-hydroxydecanamide 13: UV/Vis (1% aq. HCOOH/methanol): λmax=212, 260nm. LC-TOF-MS (ESI+): m/z 314.2029 ([M+Na]+, measured); m/z 314.2090 ([M+Na]+, calculated for C18H29NNaO2). 1H NMR (500MHz, DMSO-d6, COSY): δ [ppm] 0.86 [t, 3H, J = 6.9Hz, H-C(10)], 1.18-1.33 [m, 10H, H-C(5), H-C(6), H-C(7), H-C(8), H-C(9)], 1.39-1.50 [m, 1H, H-C(3a)], 1.52-1.63 [m, 1H, H-C(3b)], 2.02-2.10 [m, 1H, H-C(2a)], 2.10-2.18 [m, 1H, H-C(2b)], 2.69 [t, 2H, J = 7.4Hz, H-C(3’)], 3.20-3.27 [m, 2H, H-C(2’)], 3.31-3.36 [m, 1H, H-C(4)], 4.34 [d, 1H, J = 5.4Hz, H-O(11)], 7.17-7.20 [m, 2H, H-C(5’), H-C(9’)], 7.20-7.22 [m, 1H, H-C(7’)], 7.28 [d, 2H, J = 7.5Hz, H-C(6’), H-C(8’)], 7.42 [t, 1H, J = 5.5Hz, H-N(1’)]. 13C NMR (125MHz, DMSO-d6, 135-DEPT, HMBC, HMQC): δ [ppm] 13.7 [CH3, C(10)], 22.0, 25.0, 28.8, 31.3, 36.9 [CH2, C(5), C(6), C(7), C(8), C(9)], 31.9 [CH2, C(2)], 33.0 [CH2, C(3)], 35.1 [CH2, C(3’)], 39.9 [CH2, C(2’)], 68.9 [CH, C(4)], 125.9 [CH, C(7’)], 128.1 [CH, C(6’), C(8’)], 128.5 [CH, C(5’), C(9’)], 139.4 [C, C(4’)], 172.3 [C, C(1)].

N-Phenethyl-5-hydroxypentanamide 14: UV/Vis (1% aq. HCOOH/methanol): λmax=204, 216, 260nm.LC-TOF-MS (ESI+): m/z 244.1360 ([M+Na]+, measured); m/z 244.1308 ([M+Na]+, calculated for C13H19NNaO2). 1H NMR (400MHz, DMSO-d6, COSY): δ [ppm] 1.31-1.42 [m, 2H, H-C(4)], 1.43-1.56 [m, 2H, H-C(3)], 2.03 [t, 2H, J = 7.3Hz, H-C(2)], 2.69 [t, 2H, J = 7.4Hz, H-C(3’)], 3.25 [dd, 2H, J = 7.3, 13.9Hz, H-C(2’)], 3.36 [t, 2H, J = 6.4Hz, H-C(5)], 4.36 [broad s, 1H, H-O(6)], 7.16-7.21 [m, 3H, H-C(5’), H-C(7’), H-C-(9’)],7.29 [d, 2H, J = 8.4Hz, H-C(6’), H-C(8’)], 7.84 [t, 1H, J = 5.4Hz, H-N(1’)]. 13C NMR (100MHz, DMSO-d6, 135-DEPT, HMBC, HMQC): δ [ppm] 21.7 [CH2, C(3)], 32.6 [CH2, C(4)], 35.3 [CH2, C(3’)], 35.4 [CH2, C(2)], 40.0 [CH2, C(2’)], 60.6 [CH2, C(5)], 125.9 [CH, C(7’)], 128.0 [CH, C(5’), C(9’)], 128.2 [CH, C(6’), C(8’)], 139.2 [C, C(4’)], 171.5 [C, C(1)].

N-(4-Hydroxyphenethyl)-4-hydroxypentanamide 15: UV/Vis (1% aq. HCOOH/ methanol): λmax=224, 280nm.LC-TOF-MS (ESI+): m/z 238.1445 ([M+H]+, measured); m/z 238.1438 ([M+H]+, calculated for C13H20NO3). 1H NMR (400MHz, DMSO-d6, COSY): δ [ppm] 1.02 [d, 3H, J = 6.3Hz, H-C(5)], 1.43-1.48 [m, 2H, J = 7.0, 6.8Hz, H-C(3)], 1.99-2.17 [m, 2H, H-C(2)], 2.55 [t, 2H, J = 7.6Hz, H-C(3’)], 3.10-3.29 [m, 2H, H-C(2’)], 3.48-3.59 [m, 1H, H-C(4)], 4.31 [broad s, 1H, H-O(6)], 6.67 [d, 2H, J = 8.4Hz, H-C(6’), H-C(8’)], 6.96 [d, 2H, J = 8.4Hz, H-C(5’), H-C(9’)], 7.82 [broad t, 1H, J = 5.4Hz, H-N(1’)], 9.20 [broad s, 1H, H-O(10’)]. 13C NMR (100MHz, DMSO-d6, 135-DEPT, HMBC, HMQC): δ [ppm] 23.4 [CH3, C(5)], 32.0 [CH2, C(2)], 34.3 [CH2, C(3’)], 34.8 [CH2, C(3)], 40.4 [CH2, C(2’)], 65.3 [CH, C(4)], 115.0 [CH, C(6’), C(8’)], 129.28 [CH, C(5’), C(9’)], 129.34 [C, C(7’)], 155.6 [C, C(4’)], 172.1 [C, C(1)].

N-(4-Hydroxyphenethyl)-4-hydroxyhexanamide 16: UV/Vis (1% aq. HCOOH/ methanol): λmax=220, 280nm. LC-TOF-MS (ESI+): m/z 274.1423 ([M+Na]+, measured); m/z 274.1414 ([M+Na]+, calculated for C14H21NNaO3). 1H NMR (400MHz, DMSO-d6, COSY): δ [ppm] 0.85 [t, 3H, J = 7.5Hz, H-C(6)], 1.21-1.40 [m, 2H, H-C(5)], 1.40-1.50 [m, 1H, H-C(3a)], 1.53-1.63 [m, 1H, H-C(3b)], 1.94-2.22 [m, 2H, H-C(2)], 2.58 [t, 2H, J = 8.0Hz, H-C(3’)], 3.17 [dt, 2H, J = 5.3, 6.3Hz, H-C(2’)], 3.22-3.41 [m, 1H, H-C(4)], 4.38 [broad d, 1H, J = 4.0Hz, H-O(7)], 6.68 [d, 2H, J = 8.1Hz, H-C(6’), H-C(8’)], 6.98 [d, 2H, J = 8.1Hz, H-C(5’), H-C(9’)], 7.80 [broad t, 1H, J = 5.3Hz, H-N(1’)], 9.13 [s, 1H, H-O(10’)]. 13C NMR (100MHz, DMSO-d6, 135-DEPT, HMBC, HMQC): δ [ppm] 9.9 [CH3, C(6)], 29.6 [CH2, C(5)], 32.0 [CH2, C(2)], 32.4 [CH2, C(3)], 34.3 [CH2, C(3’)], 40.4 [CH2, C(2’)], 70.5 [CH, C(4)], 115.1 [CH, C(6’), C(8’)], 129.3 [CH, C(5’), C(9’)], 129.5 [C, C(4’)], 155.5 [C, C(7’)], 172.2 [C, C(1)].

N-(4-Hydroxyphenethyl)-4-hydroxydecanamide 17: UV/Vis (1% aq. HCOOH/ methanol): λmax=224, 280nm.LC-TOF-MS (ESI+): m/z 330.2044 ([M+Na]+, measured); m/z 330.2040 ([M+Na]+, calculated for C18H29NNaO3). 1H NMR (500MHz, DMSO-d6, COSY): δ [ppm] 0.90 [t, 3H, J = 6,9Hz, H-C(10)], 1.10-1.40 [m, 10H, H-C(5), H-C(6), H-C(7), H-C(8), H-C(9)], 1.40-1.50 [m, 1H, H-C(3a)], 1.53-1.62 [m, 1H, H-C(3b)], 1.99-2.09[m, 1H, H-C(2a)], 2.10-2.18 [m, 1 H, H-C(2b)], 2.56 [t, 2H, J = 7.5Hz, H-C(3’)], 3.12-3.23 [m, 2H, H-C(2’)], 3.30-3.70 [m, 1H, H-C(4)], 4.34 [d, 1H, J = 5.4Hz, H-O(11)], 6.66 [d, 2H, J = 8.4Hz, H-C(6’), H-C(8’)], 6.96 [d, 2H, J = 8.4Hz, H-C(5’), H-C(9’)], 7.42 [t, 1H, J = 5.5Hz, H-N(1’)], 9.13 [s, 1H, H-O(10’)]. 13C NMR (125MHz, DMSO-d6, 135-DEPT, HMBC, HMQC): δ [ppm] 13.9 [CH3, C(10)], 22.0, 25.2, 28.8, 37.0 [CH2, C(5), C(6), C(7), C(8), C(9)], 31.9 [CH2, C(2)], 33.0 [CH2, C(3)], 34.4 [CH2, C(3’)], 40.4 [CH2, C(2’)], 69.1 [CH, C(4)], 114.7 [CH, C(6’), C(8’)], 129.1 [CH, C(5’), C(9’)], 129.5 [C, C(4’)], 155.5 [C, C(7’)], 172.2 [C, C(1)].

N-(4-Hydroxy-3-methoxybenzyl)-4-hydroxypentanamide 18:UV/Vis (1% aq. HCOOH/ methanol): λmax=204, 224, 280nm.LC-TOF-MS (ESI+): m/z 276.1200 ([M+Na]+, measured); m/z 276.1206 ([M+Na]+, calculated for C12H16NNaO4). 1H NMR (400MHz, CD3OD, COSY): δ[ppm] 1.16 [d, 3H, J = 6.2Hz, H-C(5)], 1.64-1.81 [m, 2H, H-C(3)], 2.23-2.40 [m, 2H, H-C(2)], 3.68-3.78 [m, 1H, H-C(4)], 3.84 [s, 3H, H-C(9’)], 4.26 [s, 2H, H-C(2’)], 6.70-6.73 [m, 1H, H-C(8’)], 6.71-6.74 [m, 1H, H-C(7’)], 6.86 [s, 1H, H-C(4’)]. 13C NMR (100MHz, CD3OD, 135-DEPT, HMBC, HMQC): δ [ppm] 23.5 [CH3, C(5)], 33.7 [CH2, C(2)], 36.1 [CH2, C(3)], 44.2 [CH2, C(2’)], 55.9 [CH3, C(9’)], 68.1 [CH, C(4)], 112.6 [CH, C(4’)], 116.3 [CH, C(7’)], 121.4 [CH, C(8’)], 131.6 [C, C(3’)], 147.0 [C, C(6’)], 149.2 [C, C(5’)], 176.0 [C, C(1)].

N-(4-Hydroxy-3-methoxybenzyl)-5-hydroxypentanamide 19:UV/Vis (1% aq. HCOOH/methanol): λmax=204, 224, 280nm.LC-TOF-MS (ESI+): m/z 276.1200 ([M+Na]+, measured); m/z 276.1206 ([M+Na]+, calculated for C12H16NNaO4).1H NMR(400MHz, CD3OD, COSY): δ[ppm] 1.48-1.60 [m, 2H, H-C(4)], 1.63-1.74 [m, 2H, H-C(3)], 2.24 [t, 2H, J = 7.4Hz, H-C(2)], 3.55 [t, 2H, J = 6.4Hz, H-C(5)], 3.83 [s, 3H, H-C(9’)], 4.28 [s, 2H, H-C(2’)], 6.75-6.79 [m, 2H, H-C(7’),H-C(8’)], 6.89 [d, 1H, J = 1.3Hz, H-C(4’)]. 13C NMR (100MHz, CD3OD, HMBC, HSQC): δ[ppm] 23.5 [CH2, C(3)], 33.1 [CH2, C(4)], 36.8 [CH2, C(2)], 44.0 [CH2, C(2’)], 55.6 [CH3, C(9’)], 62.5 [CH2, C(5)], 112.5 [CH, C(4’)], 116.6 [CH, C(7’)], 121.5 [CH, C(8’)], 131.5 [C, C(3’)], 146.9 [C, C(6’)], 149.1 [C, C(5’)], 175.9 [C, C(1)].

N-(3-Hydroxy-4-methoxybenzyl)-5-hydroxypentanamide 20: UV/Vis (1% aq. HCOOH/methanol): λmax=204, 224, 280nm.LC-TOF-MS (ESI+): m/z 276.1200 ([M+Na]+, measured); m/z 276.1206 ([M+Na]+, calculated for C12H16NNaO4). 1H NMR (500MHz, DMSO-d6, COSY): δ [ppm] 1.36-1.43 [m, 2H, H-C(4)], 1.50-1.57 [m, 2H, H-C(3)], 2.10 [t, 2H, J = 7.5Hz, H-C(2)], 3.38 [dd, 2H, J = 5.3, 6.4Hz, H-C(5)], 3.72 [s, 3H, H-C(10’)], 4.10 [d, 2H, J = 5.9Hz, H-C(2’)], 4.35 [broad t, J = 5.2, H-O(6)], 6.61 [dd, 1H, J = 8.2, 1.9Hz H-C(8’)], 6.65 [d, 1H, J = 2.0Hz, H-C(4’)], 6.89 [d, 1H, J = 8.1Hz, H-C(7’)], 8.14 [t, 1H J = 5.8Hz, H-N(1’)], 8.87 [s, 1H, H-O(9’)]. 13C NMR (125MHz, DMSO-d6, HMBC, HSQC): δ [ppm] 21.9 [CH2, C(3)], 32.0 [CH2, C(4)], 35.1 [CH2, C(2)], 41.5 [CH2, C(2’)], 55.6 [CH3, C(10’)], 60.3 [CH2, C(5)], 112.1 [CH, C(7’)], 114.7 [CH, C(4’)], 117.8 [CH, C(8’)], 132.2 [C, C(3’)], 146.3 [C, C(5’)], 146.4 [C, C(6’)], 171.8 [C, C(1)].

N-(2-Hydroxyethyl)-5-hydroxypentanamide 21:LC-TOF-MS (ESI+): m/z 184.0950 ([M+Na]+, measured); m/z 184.0950 ([M+Na]+, calculated for C7H15NO3).1H NMR (400MHz, D2O, COSY): δ [ppm] 1.49-1.60 [m, 2H, H-C(4)], 1.60-1.73 [m, 2H, H-C(3)], 2.30 [t, 2H, J = 7.3Hz, H-C(2)], 3.34 [t, 2H, J = 5.6Hz, H-C(1’)], 3.61 [t, 2H, J = 6.4Hz, H-C(5)], 3.66 [t, 2H, J = 5.6Hz, H-C(2’)]. 13C NMR (100MHz, D2O, HSBC, HMQC): δ [ppm] 24.6 [CH2, C(3)], 33.6 [CH2, C(4)], 38.3 [CH2, C(2)], 44.2 [CH2, C(1’)], 62.8 [CH2, C(2’)], 64.1 [CH2, C(5)], 179.9 [C, C(1)].

N-Isobutyl-5-hydroxypentanamide 22:LC-TOF-MS (ESI+): m/z 174.1502 ([M+H]+, measured); m/z 174.1494 ([M+H]+, calculated for C9H20NO2).1H NMR (400MHz, DMSO-d6, COSY): δ [ppm] 0.82 [d, 6H, J = 6.7Hz, H-C(4’), H-C(5’)], 1.33-1.43 [m, 2H, H-C(4)], 1.45-1.55 [m, 2H H-C(3)], 1.59-1.72 [m, 1H, H-C(3’)], 2.06 [t, 2H, J = 7.4Hz, H-C(2)], 2.85 [dd, 2H, J = 6.6Hz, H-C(2’)], 3.37 [dd, 2H, J = 6.4, 11.7Hz, H-C(5)], 4.35 (t, 1H, J = 5.2Hz, H-O(6)], 7.73 [broad t, 1H, J = 5.0Hz, H-N(1’)]. 13C NMR (100MHz, DMSO-d6, HMBC):δ [ppm] 20.0 [CH3, C(4’), C(5’)], 22.0 [CH2, C(3)], 28.0 [CH, C(3’)], 32.0 [CH2, C(4)], 35.2 [CH2, C(2)], 45.8 [CH2, C(2’)], 60.3 [CH2, C(5)], 171.9 [C, C(1)].

Ethyl 2-(5-hydroxypentamido)acetate 23: LC-TOF-MS (ESI+): m/z 226.1049 ([M+Na]+, measured); m/z 226.1050 ([M+Na]+, calculated for C9H17NNaO4). 1H NMR (400MHz, CD3OD, COSY): δ [ppm] 1.25 [t, 3H, J = 7.0Hz, H-C(6’)], 1.58 [quint, 2H, J = 6.3, 7.7Hz, H-C(4)], 1.68 [quint, 2H, J = 7.3, 7.7Hz, H-C(3)], 2.28 [t, 2H, J = 7.5Hz, H-C(2)], 3.59 [t, 2H, J = 7.4Hz, H-C(5)], 3.90 [s, 2H,H-C(2’)], 4.17 [q, 2H, J = 7.0Hz, H-C(5’)]. 13C NMR (100MHz, CD3OD, 135-DEPT, HMBC, HMQC): δ [ppm] 13.1 [CH3, C(6’)], 21.8 [CH2, C(3)], 31.6 [CH2, C(4)], 35.0 [CH2, C(2)], 40.6 [CH2, C(2’)], 60.8 [CH, C(5’)], 61.1 [CH2, C(5)], 170.0 [C, C(3’)], 175.2 [C, C(1)].

Spectroscopic Data of N-Phenethylpentanamide (24)

N-Phenethylpentanamide 24:1H and 13C NMR data were well in agreement with those reported in [2], despite the signal at δ 1.62ppm, which was not observed in the current 1H NMR-spectrum. UV/Vis (1% aq. HCOOH/methanol): λmax=204, 216, 260nm.LC-TOF-MS (ESI+): m/z 206.1621 ([M+H]+, measured); m/z 206.1545 ([M+H]+, calculated for C13H20NO). 1H NMR (400MHz, DMSO-d6, COSY): δ[ppm] 0.84 [t, 3H, J = 7.4Hz, H-C(5)], 1.17-1.26 [m, 2H, H-C(4)], 1.39-1.49 [m, 2H, H-C(3)], 2.03 [t, 2H, J = 7.5Hz, H-C(2)], 2.70 [t, 2H, J = 7.4Hz, H-C(3’)], 3.26 [td, 2H, J = 5.8, 7.0Hz, H-C(2’)], 7.16-7.21 [m, 3H, H-C(5’), H-C(7’), H-C(9’)],7.28 [d, 1H, J=7.4Hz, H-C(6’), H-C(8’)], 7.83 [t, 1H, J=5.4Hz, H-N(1’)]. 13C NMR (100MHz, DMSO-d6, HMBC, HSQC): δ [ppm] 13.6 [CH3, C(5)], 21.7 [CH2, C(4)], 27.4 [CH2, C(3)], 35.0 [CH2, C(2)], 35.1 [CH2, C(3’)], 40.0 [CH2, C(2’)], 125.9 [CH, C(7’)], 128.2 [CH, C(6’), C(8’)], 128.5 [CH, C(5’), C(9’)], 139.5 [C, C(4’)], 171.9 [C, C(1)].

Spectroscopic Data of N-(4-Hydroxy-3-methoxybenzyl)pentanamide (25):

N-(4-Hydroxy-3-methoxybenzyl)pentanamide25: 1H and 13C NMR data were well in agreement with those reported in [3, 4]. UV/Vis (1% aq. HCOOH/methanol): λmax=204, 224, 236, 276nm.LC-TOF-MS (ESI+): m/z 238.1449 ([M+H]+, measured); m/z 238.1443 ([M+H]+, calculated for C13H20NO3). 1H NMR (500MHz, DMSO-d6, COSY): δ[ppm] 0.86 [t, 3H, J = 7.4Hz, H-C(5)], 1.22-1.31 [m, 2H, H-C(4)], 1.46-1.54 [m, 2H, H-C(3)], 2.11 [t, 2H, J = 7.4Hz, H-C(2)], 3.73 [s, 3H, H-C(9’)], 4.14 [d, 2H, J = 5.8Hz, H-C(2’)], 6.63 [dd, 1H, J = 1.3, 8.0Hz H-C(8’)], 6.69 [d, 1H, J = 8.0Hz, H-C(7’)], 6.79 [d, 1H, J = 1.3Hz, H-C(4’)], 8.14 [t, 1H J = 5.6Hz, H-N(1’)], 8.79 [s, 1H, H-O(10’)]. 13C NMR (125MHz, DMSO-d6, HMBC, HSQC): δ[ppm] 13.6 [CH3, C(5)], 21.7 [CH2, C(4)], 27.4 [CH2, C(3)], 35.0 [CH2, C(2)], 41.7 [CH2, C(2’)], 55.4 [CH3, C(9’)], 111.5 [CH, C(4’)], 115.1 [CH, C(7’)], 119.5 [CH, C(8’)], 130.4 [C, C(3’)], 145.7 [C, C(6’)], 147.3 [C, C(5’)], 171.8 [C, C(1)].

Literature cited in the Supporting Information:

[1]Chalid M, Heeres HJ, Broekhuis AA (2011) Ring-Opening of γ-Valerolactone with Amino Compounds. J Appl Polym Sci 129: 3556-3564

[2]Proschak A, Schultz K, Herrmann J, Dowling AJ, Brachmann AO, ffrench-Constant R, Müller R, Bode HB (2001) Cytotoxic Fatty Acid Amides from Xenorhabdus. Chem Bio Chem 12: 2011-2015 and Supporting Information.

[3]Baldessari A, Gros EG (1987) 13C NMR spectral data of some N-vanillyl-, N-piperonyl- and N-veratryl-alkylaminoalkylamides. Magn Res Chem 25: 1012–1022

[4]Barbero GF, Molinillo JMG, Varela RM, Palma, M, Macías FA, Barroso CG (2010) Application of Hansch’s Model to Capsaicinoids and Capsinoids: A Study Using the Quantitative Structure−Activity Relationship. A Novel Method for the Synthesis of Capsinoids. J Agric Food Chem 58: 3342–3349

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