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T. Keenan et al./Bioorg. Med. Chem. 6 (1998) 1309±1335
9H), 5.75 (m, 1H), 5.30 (d, J=4.8 Hz, 1H), 4.66 (s, 2H),
3.35 (d, J=9.27 Hz, 1H), 3.19 (td, J=12.4, 2.9 Hz, 1H),
2.69 (m, 2H), 2.39 (d, J=16.2 Hz, 1H), 2.30 (m, 1H),
2.10 (m, 1H), 1.90±1.60 (m, 6H), 1.50 (m, 1H), 1.19 (s,
3H), 1.17 (s, 3H), 0.85 (t, J=7.4 Hz, 3H); 13C NMR
(CDCl3, 75 MHz) 208.0, 172.3, 169.8, 167.9, 158.2,
142.2, 141.1, 130.2, 128.9, 128.7, 126.5, 120.3, 115.5,
111.8, 65.5, 57.2, 52.0, 47.2, 44.6, 38.3, 33.0, 32.9, 32.1,
27.0, 25.3, 25.2, 23.9, 23.4, 21.5, 9.1; HRMS (FAB):
(M+Na)+ calcd: 546.2468, recorded: 546.2461.
product (315 mg, 86%) as a foam: TLC (MeOH/CHCl3,
15/85) Rf=0.35; IR (neat) 2940, 1740, 1640, 1515, 1445,
1
1260, 1160 cm 1; H NMR (CDCl3, 300 MHz) 8.00 (br
s, 1H), 7.35±6.70 (m, 7H), 5.82 (m, 1H), 5.33 (d,
J=4.5 Hz, 1H), 4.71 (m, 2H), 3.89 (s, 3H), 3.87 (s, 3H),
3.38 (d, J=12.6 Hz, 1H), 3.24 (td, J=12.3, 2.7 Hz, 1H),
2.60 (m, 2H), 2.45±2.05 (m, 3H), 1.70 (m, 6H), 1.45 (m,
2H), 1.23 (s, 3H), 1.21 (s, 3H), 0.89 (t, J=7.4 Hz, 3H);
1H NMR (CD3OD, 300 MHz) 7.30 (t, J=7.9 Hz, 1H),
7.00±6.77 (m, 5H), 6.72 (dd, J=8.1, 1.8 Hz, 1H), 5.80±
5.74 (m, 1H), 5.24 (d, J=4.5 Hz, 1H), 4.69 (s, 2H), 3.82
(s, 3H), 3.80 (s, 3H), 3.38 (dd, J=13.3, 8.5 Hz, 1H), 3.18
(td, J=12.8, 2.9 Hz, 1H), 2.69±2.54 (m, 2H), 2.37±2.15
(m, 2H), 2.13±2.01 (m, 1H), 1.79±1.61 (m, 5H), 1.53±
1.30 (m, 2H), 1.25 (s, 3H), 1.23 (s, 3H), 0.90 (t,
J=7.4 Hz, 3H); 13C NMR (CDCl3, 75 MHz) 208.0,
172.0, 169.8, 167.8, 158.2, 149.4, 147.8, 142.2, 133.7,
130.2, 129.4, 128.6, 125.7, 120.6, 120.3, 115.5, 112.2,
111.8, 111.7, 108.2, 65.5, 56.3, 51.9, 47.2, 44.6, 38.5,
(1R)-1-[3-(Carboxymethoxy)phenyl]-3-(3,4,5-trimethoxy-
phenyl)-1-propanyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-
2-piperidinecarboxylate (2b). General procedure G was
used for the acidolysis of 15b. The crude product was
chromatographed (10% MeOH/CH2Cl2) to aord pro-
duct (358 mg, 98%) as a white foam: TLC (MeOH/
CHCl3, 15/85) Rf=0.40; IR (neat) 3445, 2940, 1735,
;
1H NMR (CDCl3,
1
1700, 1635, 1460, 1210, 1130 cm
300 MHz) 7.30±6.80 (m, 4H), 6.39 (s, 2H), 5.82 (m, 1H),
5.33 (d, J=4.6 Hz, 1H), 4.70 (m, 2H), 3.86 (s, 6H), 3.84
(s, 3H), 3.38 (d, J=12.6 Hz, 1H), 3.22 (td, J=12.8,
3.1 Hz, 1H), 2.60 (m, 2H), 2.45±2.05 (m, 3H), 1.70 (m,
6H), 1.45 (m, 2H), 1.23 (s, 3H), 1.21 (s, 3H), 0.89 (t,
J=7.4 Hz, 3H); 13C NMR (CDCl3, 75 MHz) 208.0,
175.0, 171.7, 169.8, 167.8, 158.2, 153.6, 142.1, 136.9,
130.2, 129.4, 128.6, 125.7, 120.3, 115.5, 111.8, 107.9,
105.8, 65.6, 61.2, 56.5, 52.0, 47.2, 44.6, 38.3, 32.9, 32.5,
27.0, 25.3, 23.8, 23.4, 21.5, 9.1; HRMS (FAB):
(M+Na)+ calcd: 636.2785, recorded: 636.2756.
32.9, 31.7, 28.4, 27.0, 25.3, 23.9, 23.4, 21.8, 21.5, 9.1; 13
C
NMR (CD3OD, 75 MHz) 207.9, 171.4, 169.8, 167.9,
158.5, 149.3, 147.7, 142.0, 134.1, 129.6, 120.5, 119.7,
114.4, 112.7, 112.4, 112.1, 76.8, 64.8, 55.4, 55.3, 51.6,
46.5, 44.6, 37.9, 32.4, 31.0, 26.1, 24.7, 22.7, 22.4, 20.9,
7.9; HRMS (FAB): (M+Na)+ calcd: 606.2679, recor-
ded: 606.2692.
(1R)-1-[3-(Carboxymethoxy)phenyl]-3-(4-methoxyphenyl)-
1-propanyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-piper-
idinecarboxylate (2e). General procedure G was used
for the acidolysis of 15e. The crude product was chro-
matographed (10% MeOH/CH2Cl2) to aord product
(45 mg, 71%) as a foam: TLC (MeOH/CHCl3, 15/85)
Rf=0.35; IR (neat) 2940, 1735, 1700, 1635, 1455,
1210 cm 1; 1H NMR (CD3OD, 300 MHz) 7.14±7.00 (m,
1H), 6.85 (d, J=8.1 Hz, 2H), 6.77±6.67 (m, 3H), 6.61
(d, J=8.2 Hz, 2H), 5.55±5.50 (m, 1H), 5.01 (d,
J=4.5 Hz, 1H), 4.45 (s, 2H), 3.54 (s, 3H), 3.18 (d,
J=13.0 Hz, 1H), 2.95 (t, J=12.6 Hz, 1H), 2.45±2.25
(m, 2H), 2.20±1.80 (m, 3H), 1.60±1.40 (m, 5H), 1.35±
1.10 (m, 2H), 1.02 (s, 3H), 1.00 (s, 3H), 0.67 (t,
J=7.4 Hz, 3H); 13C NMR (CD3OD, 75 MHz) 210.0,
171.9, 170.1, 160.7, 160.5, 144.1, 135.3, 131.8, 131.4,
121.85, 116.6, 116.0, 116.0, 114.9, 79.1, 56.7, 53.8, 48.7,
46.7, 40.2, 34.6, 32.8, 28.3, 26.9, 24.9, 24.6, 23.1, 10.1;
LRMS (ES+): (M+Na)+ 576; (ES ): (M H) 552;
HRMS (FAB): (M H) calcd: 552.2597, recorded:
552.2585.
(1R)-1-[3-(Carboxymethoxy)phenyl]-3-(1,3-benzodioxol-
5-yl)-1-propanyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-
piperidinecarboxylate (2c). General procedure G was
used for the acidolysis of 15c. The crude product was
chromatographed (10% MeOH/CH2Cl2) to aord pro-
duct (483 mg, 85%) as a colorless oil: TLC (MeOH/
CHCl3, 15/85) Rf=0.40; IR (neat) 3420, 2940, 1735,
1
1700, 1640, 1490, 1440, 1245, 1040 cm
;
1H NMR
(CDCl3, 300 MHz) 7.12 (t, J=6.7 Hz, 1H), 6.92±6.81
(m, 3H), 6.68±6.52 (m, 3H), 5.86 (s, 2H), 5.73 (t,
J=7.2 Hz, 1H), 5.33 (s, 1H), 4.40 (s, 2H), 3.34 (d,
J=12.2 Hz, 1H), 3.19 (t, J=12.0 Hz, 1H), 2.54±2.46 (m,
2H), 2.34 (d, J=12.6 Hz, 1H), 2.24±2.00 (m, 2H), 1.73±
1.32 (m, 7H), 1.18 (s, 3H), 1.16 (s, 3H), 0.84 (t,
J=7.3 Hz, 3H); 13C NMR (CDCl3, 75 MHz) 208.0,
169.9, 167.79, 158.3, 148.0, 146.2, 141.9, 135.0, 130.1,
121.5, 109.1, 108.6, 107.2, 101.2, 77.0, 51.9, 47.0, 44.6,
38.6, 32.9, 31.8, 26.9, 25.3, 23.9, 23.3, 21.6, 9.1. HRMS
(FAB): (M H) calcd: 566.2390, recorded: 566.2365.
(1R)-1-[3-(Carboxymethoxy)phenyl]-3-(3-pyridinyl)-1-prop-
anyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-piperidine-
carboxylate (2f). General procedure G was used for the
acidolysis of 15f. The crude product was not chromato-
graphed. Product (424 mg, 96%, as tri¯uoroacetic acid
salt) was obtained as a foam: 1H NMR (CDCl3,
300 MHz) 8.75 (s, 1H), 8.67 (d, J=10.4 Hz, 1H), 8.23
(1R)-1-[3-(Carboxymethoxy)phenyl]-3-(3,4-dimethoxy-
phenyl)-1-propanyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-
2-piperidinecarboxylate (2d). General procedure G was
used for the acidolysis of 15d. The crude product was
chromatographed (10% MeOH/CH2Cl2) to aord