9040 J . Org. Chem., Vol. 66, No. 26, 2001
Notes
solution of anthranilamide (2, 6.80 g, 50 mmol) in benzene-1,4-
dioxane mixture (75 mL, 2:1) in a dropwise fashion with constant
stirring at room temperature. The reaction mixture was further
stirred for 2 h, and the formed precipitate was filtered under
vacuum and washed with ether (50 mL). The obtained compound
4b was used for the next step without any further purification.
Analytically pure 4b was obtained by recrystallization from ethyl
cm-1. Anal. Calcd for C11H12N2O3: C, 60.00; H, 5.49; N, 12.72.
Found: C, 59.78; H, 5.29; N, 12.83.
Similarly, 5a gave pegamine (7a ): 93% yield; mp 163-165
°C (ethyl acetate) (lit.3b 160-161 °C); 1H NMR (CD3OD, 200
MHz) δ 2.00 (quintet, J ) 6 Hz, 2H), 2.77 (t, J ) 8 Hz, 2H), 3.66
(t, J ) 6 Hz, 2H), 7.48 (t, J ) 8 Hz, 1H), 7.63 (d, J ) 8 Hz, 1H),
7.79 (t, J ) 8 Hz, 1H), 8.17 (d, J ) 8 Hz, 1H); 13C NMR (CD3-
OD, 50 MHz) δ 31.3, 33.0, 62.1, 121.8, 127.1, 127.3, 127.4, 127.6,
135.9, 150.0, 159.3. MS (m/e) 204, 187, 173, 160, 132, 119, 90,
77, 63. IR (Nujol) νmax 3395, 3319, 3173, 3123, 3038, 1695, 1682
cm-1. Anal. Calcd for C11H12N2O2: C, 64.70; H, 5.92; N, 13.72.
Found: C, 64.93; H, 6.11; N, 14.00.
acetate. 4b: 14.4 g (98% yield); mp 152-153 °C; [R]20 ) -88.7
D
(c 0.6, acetone); 1H NMR (CD3OD, 200 MHz) δ 2.26 (s, 3H), 2.92
(d, J ) 6 Hz, 1H), 2.95 (d, J ) 2 Hz, 1H), 5.53 (dd, J ) 8 and 4
Hz, 1H), 7.16 (t, J ) 8 Hz, 1H), 7.49 (t, J ) 8 Hz, 1H), 7.76 (d,
J ) 8 Hz, 1H), 8.51 (d, J ) 8 Hz, 1H); 13C NMR (CD3OD, 75
MHz) δ 20.9, 37.5, 71.8, 121.7, 122.0, 124.7, 129.5, 133.6, 139.8,
169.8, 171.6, 173.0, 173.3. MS (m/e) 294, 277, 259, 235, 216, 198,
163, 146, 136, 119, 92, 71, 65. IR (Nujol) νmax 3445, 3396, 3336,
3188, 1747, 1693, 1666, 1660 cm-1. Anal. Calcd for C13H14N2O6:
C, 53.06; H, 4.80; N, 9.52. Found: C, 53.13; H, 4.71; N, 9.74.
2,3-Dih ydr o-3(S)-h ydr oxypyr r olo[2,1-b]qu in azolin -9(1H)-
on e [(-)-Va sicin on e, 1b]. To the solution of 7b (0.55 g, 2.50
mmol) and TPP (0.85 g, 3.25 mmol) in THF (7 mL) was added a
solution of DEAD (0.48 g, 2.75 mmol) in THF (5 mL) in a
dropwise fashion with continuous stirring at room temperature,
and the reaction mixture was further stirred for 1 h. The reaction
mixture was concentrated in vacuo, and the residue was chro-
matographed on silica gel using petroleum ether and ethyl
acetate (1:1) to obtain (-)-vasicinone (1b): 0.455 g (90% yield);
Similarly, the reaction of succinic anhydride (3a ) with an-
thranilamide (2) furnished o-amidosuccinanilic acid (4a ): 98%
1
yield; mp 197-198 °C (MeOH); H NMR (CD3OD, 200 MHz) δ
2.68 (s, 4H), 7.13 (t, J ) 8 Hz, 1H), 7.47 (t, J ) 8 Hz, 1H), 7.73
(d, J ) 8 Hz, 1H), 8.37 (d, J ) 8 Hz, 1H); 13C NMR (DMSO-d6,
50 MHz) δ 28.9, 32.2, 119.7, 120.2, 122.3, 128.5, 132.1, 139.6,
169.9, 170.8, 173.5. MS (m/e) 236, 218, 202, 174, 146, 136, 119,
107, 101, 90, 73, 65, 55. IR (Nujol) νmax 3414, 3346, 3242, 3217,
3165, 1709, 1680, 1659, 1616 cm-1. Anal. Calcd for C11H12N2O4:
C, 55.93; H, 5.12; N, 11.86. Found: C, 56.21; H, 5.29; N, 12.01.
mp 205-207 °C (EtOH) (lit.18 200-201 °C); [R]20 ) -105.6 (c
D
1.0, CHCl3) [lit.18 -105.0 (c 1.0, CHCl3)]; H NMR (CDCl3, 200
1
MHz) δ 2.20-2.45 (m, 1H), 2.60-2.80 (m, 1H), 3.90-4.15 (m,
1H), 4.30-4.50 (m, 1H), 5.27 (t, J ) 6 Hz, 1H), 7.40-7.60 (m,
1H), 7.65-7.85 (m, 2H), 8.31 (d, J ) 6 Hz, 1H); 13C NMR (CDCl3,
75 MHz) δ 29.4, 43.5, 72.0, 121.1, 126.7, 126.8, 126.9, 134.4,
148.6, 160.1, 160.6. MS (m/e) 202, 185, 174, 146, 130, 119, 102,
90, 76, 63, 55. IR (Nujol) νmax 3169, 1683, 1635, 1463 cm-1. Anal.
Calcd for C11H10N2O2: C, 65.34; H, 4.99; N, 13.85. Found: C,
65.24; H, 5.07; N, 13.87.
Meth yl â (S)-Acetoxy-o-a m id osu ccin a n ila te (5b). To a
solution of diazomethane in ether (50 mL) was added acid 4b
(5.0 g, 17 mmol) at 0 °C, and the reaction mixture was further
stirred at room temperature until the starting acid was com-
pletely consumed (1 h). An excess of diazomethane was quenched
with acetic acid, and the organic layer was washed with water,
brine, and dried over Na2SO4. The organic layer was concen-
trated in vacuo followed by silica gel column chromatographic
purification of the residue using a petroleum ether and ethyl
acetate mixture (3:1) to give pure 5b: 5.13 g (98% yield); mp
80-82 °C (C6H6); [R]20D ) -65.7 (c 1.2, CHCl3); 1H NMR (CDCl3,
300 MHz) δ 2.30 (s, 3H), 2.90-3.10 (m, 2H), 3.71 (s, 3H), 5.68
(dd, J ) 9 and 6 Hz, 1H), 5.57-6.00 (bs, 1H), 6.00-6.50 (bs,
1H), 7.11 (t, J ) 6 Hz, 1H), 7.50 (t, J ) 9 Hz, 1H), 7.55 (d, J )
9 Hz, 1H), 8.64 (d, J ) 9 Hz, 1H), 11.94 (s, 1H); 13C NMR (CDCl3,
50 MHz) δ 20.7, 36.4, 51.9, 70.0, 119.0, 121.0, 123.2, 127.5, 133.0,
138.9, 167.6, 169.9, 170.1, 171.1. MS (m/e) 277, 180, 147, 131,
Similarly, the reaction of 7a furnished deoxyvasicinone (1a ):
1
95% yield; mp 106-108 °C (C6H6) (lit.18 104-106 °C); H NMR
(CDCl3, 200 MHz) δ 2.30 (quintet, J ) 8 Hz, 2H), 3.19 (t, J ) 8
Hz, 2H), 4.22 (t, J ) 8 Hz, 2H), 7.46 (t, J ) 8 Hz, 1H), 7.55-
7.85 (m, 2H), 8.29 (d, J ) 8 Hz, 1H); 13C NMR (CDCl3, 50 MHz)
δ 19.3, 32.3, 46.3, 120.3, 126.0, 126.2, 126.6, 133.9, 149.0, 159.3,
160.7. MS (m/e) 185, 167, 160, 144, 130, 116, 102, 90, 76, 63. IR
(Nujol) νmax 1674, 1620 cm-1. Anal. Calcd for C11H10N2O: C,
70.95; H, 5.41; N, 15.04. Found: C, 71.01; H, 5.45; N, 15.14.
MTP A-ester of (()-Va sicin on e. To a solution of (()-vasi-
cinone (10 mg, 0.05 mmol) and pyridine (0.1 mL) in DCM (1 mL)
was added (S)-MTPA-Cl solution in DCM (0.08 M, 1 mL), and
the reaction mixture was refluxed for 15 h. The reaction mixture
was concentrated in vacuo, and the residue was dissolved in
diethyl ether (15 mL). The organic layer was washed with CuSO4
solution, water, aqueous bicarbonate, water, and brine and dried
over Na2SO4. Concentration of the organic layer in vacuo
furnished the product as a thick oil (16 mg). 1H NMR (CDCl3,
200 MHz) δ 2.15-2.55 (m, 2H), 2.60-2.90 (m, 2H), 3.57 (s, 3H),
3.66 (s, 3H), 4.00-4.50 (m, 4H), 6.30-6.55 (m, 2H), 7.20-7.90
(m, 16H), 8.31 (d, J ) 8 Hz, 2H). MS (m/e) 418, 388, 359, 201,
189, 184, 119, 105, 91, 77. Anal. Calcd for C21H17F3N2O4: C,
60.29; H, 4.09; N, 6.70. Found: C, 60.33; H, 3.97; N, 6.91.
Similarly, the MTPA-ester of (-)-vasicinone (1b) was pre-
107, 93, 81, 59. IR (Nujol) νmax 3448, 3340, 1740, 1737, 1662 cm-1
.
Anal. Calcd for C14H16N2O6: C, 54.54; H, 5.23; N, 9.09. Found:
C, 54.33; H, 5.09; N, 9.14.
Similarly, 4a furnished 5a : 98% yield; mp 133-135 °C (C6H6);
1H NMR (CDCl3, 200 MHz) δ 2.75 (s, 4H), 3.71 (s, 3H), 5.50-
6.00 (bs, 1H), 6.00-6.50 (bs, 1H), 7.08 (t, J ) 8 Hz, 1H), 7.40-
7.60 (m, 2H), 8.61 (d, J ) 10 Hz, 1H), 11.25 (bs, 1H); 13C NMR
(CDCl3, 50 MHz) δ 29.1, 32.6, 51.8, 118.8, 121.6, 122.6, 127.4,
133.1, 140.0, 170.2, 171.4, 173.1. MS (m/e) 250, 219, 202, 174,
146, 136, 119, 100, 92, 72, 55. IR (Nujol) νmax 3358-3192, 1745,
1682, 1666 cm-1. Anal. Calcd for C12H14N2O4: C, 57.59; H, 5.64;
N, 11.19. Found: C, 57.49; H, 5.60; N, 11.32.
1
pared: mp 172-174 °C; H NMR (CDCl3, 500 MHz) δ 2.43 (m,
1H), 2.75 (m, 1H), 3.57 (s, 2.955H), 3.65 (s, 0.045H), 4.22 (m,
1H), 4.30 (m, 1H), 6.37 (m, 0.985H), 6.43 (m, 0.015H), 7.35-
7.80 (m, 8H), 8.30 (d, J ) 10 Hz, 1H). MS (m/e) 418, 388, 359,
201, 189, 184, 119, 105, 91, 77. Anal. Calcd for C21H17F3N2O4:
C, 60.29; H, 4.09; N, 6.70. Found: C, 60.12; H, 4.17; N, 6.77.
2-[1(S),3-Dih yd r oxyp r op yl]qu in a zolin -4(1H)-on e (7b). To
the slurry of LAH (0.76 g, 20 mmol) in THF (20 mL) was added
a solution of ester 5b (3.08 g, 10 mmol) in THF (30 mL) in a
dropwise fashion at 0-5 °C over a period of 30 min with
continuous stirring. The reaction mixture was further stirred
at room temperature for 1 h. The reaction was slowly quenched
with water (25 mL) and further stirred for 1 h at room
temperature. Saturated NH4Cl solution (10 mL) was added to
the reaction mixture, and then it was completely concentrated
under vacuum and dried to the pump. The residue was stirred
with THF (75 mL) for 1 h, and the organic layer was filtered
through Celite, dried over Na2SO4, and concentrated in vacuo.
The obtained crude product was purified by silica gel column
chromatography using a mixture of ethyl acetate and methanol
(99:1) to furnish pegamine derivative 7b: 2.03 g (92% yield);
Ack n ow led gm en t. S.B.M. thanks CSIR, New Delhi,
for the award of a research fellowship. N.P.A. thanks
the Department of Science and Technology, New Delhi,
for financial support. We thank Dr. S. P. Chavan and
Mr. R. Sivappa, OCT, NCL, Pune for the authentic
sample of (()-vasicinone. We thank Dr. K. N. Ganesh,
Head, Division of Organic Chemistry (Synthesis), for the
constant encouragement.
mp 134-136 °C (ethyl acetate); [R]20 ) -22.6 (c 1.0, MeOH);
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
1, 4, 5, 7, and MTPA esters of (()-vasicinone and (-)-1b; 13C
NMR spectra of 1, 4b, 5b, and 7; and mass spectra of 1, 4b, 5,
and 7. This material is available free of charge via the Internet
at http://pubs.acs.org.
D
1H NMR (CD3OD, 200 MHz) δ 1.85-2.25 (m, 2H), 3.78 (t, J ) 6
Hz, 2H), 4.65-4.85 (m, 1H), 7.49 (t, J ) 8 Hz, 1H), 7.66 (d, J )
8 Hz, 1H), 7.79 (t, J ) 8 Hz, 1H), 8.18 (d, J ) 8 Hz, 1H); 13C
NMR (CD3OD, 75 MHz) δ 39.5, 59.4, 70.1, 122.2, 127.2, 127.4,
127.8, 135.9, 149.5, 160.9, 164.3. MS (m/e) 220, 198, 170, 158,
132, 107, 81, 57. IR (Nujol) νmax 3373, 3276, 3119, 1683, 1613
J O010727L