1
134 J ournal of Natural Products, 2004, Vol. 67, No. 7
Maskey et al.
-5),
+
13C NMR/APT (DMSO-d
146.49 (C -6), 146.06 (C
135.23 (CH-2), 134.7 (CH-9), 134.40 (C
124.4 (CH-11), 124.4 (CH-4), 123.9 (C
121.02 (C -11a), 115.41 (C -4a), 16.69 (1-CH
EIMS (70 eV) m/z (%) 291.2 [M] (100), 274.1 [M - NH
2
C
29 [M + Na] (8); ESI-HRMS 206.1034 (calcd 206.105527 for
6
, 125.707 MHz) δ 159.47 (C
-12), 143.9 (C -1a), 136.81 (C -7a),
-1), 125.83 (CH-10),
-8), 122.12 (CH-3),
), 16.46 (8-CH );
] (30),
262.2 [M - (HCdO)] (63), (12), 159.1 (7), 145.6 (6), 105.1 (8),
77.0 (5); EIHRS found 291.1008, calcd 291.1007 for C17 ).
q
11
H
14
N
2
O
2
), 229.0932 (calcd 229.095297 for C11
H
14
N
2
O
2
Na,
q
q
q
q
+
[
M + Na] ).
R*,R*)-2-(1-H yd r oxyet h yl)-2-m et h yl-2,3-d ih yd r o-1H -
qu in a zolin -4-on e (5): colorless solid, R -17.5°
) 0.28; [R]20
c 0.2, MeOH); UV (MeOH) λmax (log ꢀ) 253 (3.51), 350 (3.25);
IR (KBr) νmax 3402, 2980, 2943, 1654, 1636, 1596, 1517, 1487,
q
(
q
f
D
q
q
3
3
+
+
3
(
+
-
1
1
384, 1334, 1275, 1152, 1101, 1032, 911, 755, 702, 559 cm
;
13 3 2
H N O
1
3
4
H NMR (acetone-d , 300.2 MHz) δ 7.63 (dd, J ) 7.9 Hz, J )
6
3
1
7
.6 Hz, 1 H, H-5), 7.19 (br s, 1 H, NH), 7.19 (ddd, J ) 8.2 and
4 3 4
Ack n ow led gm en t. We would like to thank H. Frauendorf
and R. Machinek for the MS and NMR measurements, and
Mrs. N. Sieck for assistance in microbiological work and
isolation. Special thanks to Dr. F. Huth (bioLeads GmbH,
Heidelberg, Germany) for the measurement by ESI-HRMS.
M.S. is thankful to the Egyptian government for a Ph.D.
scholarship. This work was supported by a grant from the
Bundesministerium f u¨ r Bildung und Forschung (BMBF, grant
.2 Hz, J ) 1.6 Hz, 1 H, H-7), 6.75 (dd, J ) 8.2 Hz, J ) 1.1
3
4
Hz, 1 H, H-8), 6.63 (ddd, J ) 7.9 and 7.2 Hz, J ) 1.1 Hz, 1
3
H, H-6), 5.87 (br, 1 H, NH), 4.43 (s br, 1 H, OH), 3.90 (q, J )
3
6
.4 Hz, 1 H, H-1′), 1.46 (s, 3 H, 2-CH
3
), 1.20 (d, J ) 6.4 Hz, 3
1
3
H, H
3
-2′); C NMR (acetone-d
6
, 75.5 MHz) δ 164.2 (CO), 148.0
(C-8a), 134.2 (CH-7), 128.2 (CH-5), 117.4 (CH-8), 114.8 (CH-
6
), 114.8 (C-4a), 72.9 (C-2), 72.9 (CH-1′), 23.5 (2-CH
3
), 17.8
OD, 75.5 MHz) δ 166.5 (CO), 148.7 (C-
a), 135.3 (CH-7), 128.4 (CH-5), 118.0 (CH-8), 115.1 (CH-6),
14.3 (C-4a), 73.3 (CH-1′), 73.1 (C-2), 23.0 (2-CH ), 17.5 (CH
1
3
3 3
(CH -2′); C NMR (CD
0
3F0346A).
8
1
2
3
3
-
+
′); EIMS (70 eV) m/z (%) 161 [M - CHOHCH ] (100), 221
3
Refer en ces a n d Notes
(9), 208 (4), 169 (8), 154 (4), 130 (48), 103 (3), 83 (8), 77 (4), 57
(
1) Fischer, G.; M u¨ ller, T.; Ostrowski, R.; Schwalbe, R.; Dott, W.
Schriftenr. Vereins Wasser-, Boden- Lufthygiene 1999, 104, 149-162.
(2) Dai, J .-R.; Carte, B. K.; Sidebottom, P. S.; Yew, A. L. S.; Ng, S.-B.;
Huang, Y.; Butler, M. S. J . Nat. Prod. 2001, 64, 125-126.
3) Danz, S. S.; Wippich, P.; Brattstrom, A.; Hamburger, M. Planta Med.
+
+
(
3); (+)-ESI-MS m/z (%) 641 [3M + Na] (8), 435 [2M + Na]
+
(100), 229 [M + Na] (10); ESI-HRMS 206.1034 (calcd 206.10553
for C11
14 2 2 14 2 2
H N O ), 229.0932 (calcd 229.09530 for C11H N O Na,
(
+
[
M + Na] ).
-Meth yl-1H-qu in azolin e-2,4-dion e (6): R
0% MeOH), UV absorbing at 254 nm, no color reaction with
2
001, 411-416.
5
f
) 0.50 (CHCl
3
/
(4) Faskhutdinov, M. F.; Telezhenetskaya, M. V.; Levkorich, M. G.;
Abdullaev, N. D. Chem. Nat. Compd. 2000, 36, 602-605.
(5) Tulyaganov, T. S.; Nazarov, O. M. Chem. Nat. Compd. 2000, 36, 393-
1
1
anisaldehyde/sulfuric acid or Ehrlich’s reagent; H NMR
3
95.
3
4
(acetone-d
6
, 300.2 MHz) δ 7.57 (dd, J ) 7.9 Hz, J ) 1.5 Hz,
3 3
(
6) Sarkar, M.; Chakraborty, D. P. Phytochemistry 1977, 16, 2007-2008.
1
H, H-8), 7.30 (t, J ) 7.9 Hz, 1 H, H-7), 7.19 (dd, J ) 7.9
(7) Li, L.; Yang, G.; Dang, T.; Chen, Z. Zhongcaoyao 1996, 27, 381-391.
4
13
(8) Niederer, D.; Tamm, C.; Z u¨ rcher, W. Tetrahedron Lett. 1992, 33,
Hz, J ) 1.5 Hz, 1 H, H-6), 2.48 (s, 3 H, 5-CH
3
); C NMR
, 50.3 MHz) δ 161.5 (C-4), 152.1 (C-2), 139.7 (C-
a), 137.7 (C-5), 126.7 (CH-7), 121.5 (C-4a), 117.2 (CH-6), 116.1
3
997-4000.
(acetone-d
6
(
9) Shaaban, M.; Maskey, R. P.; Wagner-D o¨ bler,I.; Laatsch, H. J . Nat.
8
Prod. 2002, 65, 1660-1663.
+
(CH-8), 21.1 (5-CH
3
); EIMS (70 eV) m/z (%) 176 [M] (100),
+ (21), 151 (30), 134 [M - OdCdN]+ (22), 121
3
62 [M - CH ]
(10) Montginoul, C.; Pastor, G.; Vigne, C.; Giral, L. Ann. Pharm. Fr. 1989,
46, 223-232.
11) J acobs, R. T.; Folmer, J .; Simpson, T. R.; Chaudhari, B.; Frazee, W.
J .; Davenport, T. W. WO 2001021598, 2001.
12) Yoshida, S.; Aoyagi, T.; Harada, S.; Matsuda, N.; Ikeda, T.; Naganawa,
H.; Hamada, M.; Takeuchi, T. J . Antibiot. 1991, 44, 111-112.
13) Opitz, M.; Pachaly, P.; Sin, K. S. Pharmazie 1999, 54, 218-223.
14) Latif, Z.; Hartley, T. G.; Rice, M. J .; Waigh; R. D.; Waterman, P. G.
Biochem. Syst. Ecol. 1998, 26, 467-468.
(15) Hall, A.; Romanova, T. Exp. Parasitol. 1990, 70, 35-42.
(16) Cardellina, R. V.; Borisova, T. A.; Vlasov, P. V.; Machackova, I.;
Andrianov; V. M.; Piruzyan, E. S.; Kefeli, V. I. J . Nat. Prod. 1986,
1
(
(
(
(
3
13), 107 (24), 91 (16.5), 65 (10), 51 (11); DCIMS (NH ) m/z
+
+
+
%) 353 [2M + H] (4), 194 ([M + NH
100); ESI-HRMS 176.0590 (calcd 176.05857 for C
-Meth yl-1H-qu in a zolin e-2,4-d ion e (7). A mixture of 4
4
]
(28), 177 [M + H]
(
9
8 2 2
H N O
).
(
(
8
mmol (600 mg) of 3-methylanthranilic acid and 8 mmol (480
mg) of urea was molten together and kept for 5 min at about
1
25 °C. After cooling to room temperature, the resulting solid
was triturated with 200 mL of CHCl /MeOH (87:13) and the
undissolved material discarded. Separation of the crude
product by PTLC (20 × 20 cm, CHCl /10% MeOH) and
Sephadex LH-20 (CHCl /MeOH, 6:4) afforded 500 mg (71%)
3
4
9, 1065-1067.
(
17) Bernards, M. A.; Razem, F. A. Phytochemistry 2001, 57, 1115-1122.
3
(18) Kelley, C. J .; Harruff, R. C.; Carmack, M. J . Org. Chem. 1976, 43,
449-455.
3
(
19) Ayer, W. A.; Tfovonov, L. S. Phytochemistry 1995, 39, 371-372.
20) Buchanan, M. S.; Steglich, W.; Anke, T. J . Biosci. 1999, 54, 463-
of 7 as colorless needles after crystallization from MeOH.
Purification of the mother liquor gave 10 mg of 11 as a yellow
byproduct.
(
4
68.
(21) Kunimoto, S.; Xu, C. Z.; Naganawa, H.; Hamada, M.; Masuda, T.;
Takeuchi, T.; Umezawa, H. J . Antibiot. 1987, 40, 1651-1652.
22) Dembitsky, V. M.; Shkrob, I.; Lev, O. J . Chem. Ecol. 2000, 26, 1359-
7
: R
f
) 0.52 (CHCl
3
/10% MeOH, mp 297-299 °C; IR (KBr)
(
ν
1
3
max 3508, 3428, 3025, 2845, 1721, 1683, 1635, 1507, 1459,
418, 1326, 1085, 882, 752, 532 cm
00.2 MHz) δ 10.80 (br s, 2 H, 2 NH), 7.88 (dd, J ) 7.6 Hz,
1
366.
-
1
1
6
; H NMR (DMSO-d ,
(
23) H o¨ fle, G.; Wolf, H. Liebigs Ann. Chem. 1983, 835-843.
3
(24) Shikishima, Y.; Takaishi, Y.; Honda, G.; Ito, M.; Takeda, Y.; Kodzhi-
matov, O. K.; Ashurmetov, O. Phytochemistry 2001, 57, 135-141.
(25) B o¨ hlendorf B.; Forche, E.; Bedorf, N.; Gerth, K.; Irschik, H.; J ansen,
R.; Kunze, B.; H o¨ fle, G. Liebigs Ann. Chem. 1996, 49-53.
4
3
4
J ) 1.1 Hz, 1 H, H-5), 7.54 (dd, J ) 7.6 Hz, J ) 1 Hz, 1 H,
3
1
H-7), 7.09 (t, J ) 7.6 Hz, 1 H, H-6), 2.36 (s, 3 H, 8-CH
NMR (acetone-d
3
); H
, 300.2 MHz) δ 10.10 (br s, 1 H, NH), 9.25
6
(
26) Ayer, W. A.; Browne, L. M.; Feng, M.-C.; Orszanska, H.; Safedi-Ghomi,
3
4
(
7
br s, 1 H, NH), 7.88 (dd, J ) 7.6 Hz, J ) 1.1 Hz, 1 H, H-5),
H. Can. J . Chem. 1986, 64, 904-908.
3
4
3
(27) Huang, Q.; Tezuka, Y.; Hatanaka, Y.; Kikuchi, T.; Nishi, A.; Tubaki,
.54 (dd, J ) 7.6 Hz, J ) 1 Hz, 1 H, H-7), 7.12 (t, J ) 7.6
13
K. Chem. Pharm. Bull. 1995, 43, 1035-1038.
3 6
Hz, 1 H, H-6), 2.47 (s, 3 H, 8-CH ); C NMR (DMSO-d , 50.3
MHz) δ 162.9 (CO-4), 150.4 (CO-2), 139.1 (C-8a), 135.9 (CH-
7
(
28) Laatsch, H. AntiBase 2003, A Data Base for Rapid Structural
Determination of Microbial Natural Products; Chemical Concepts:
Weinheim, Germany, 2003, and annual updates.
), 124.7 (CH-5), 124.0 (C-8), 122.0 (CH-6), 114.6 (C-4a), 17.0
+
(29) Dictionary of Natural Products on CD-ROM; Chapman & Hall:
(
3
CH -5); EIMS (70 eV) m/z (%) 176 [M] (100), 133 [M -
Chemical Database, Version 8.2, 2000.
+
+
CdO-NH] (28), 105 [M - (CdO-NH-CdO)] (63), 77.0 (14),
5
6
30) Pouchert, C. J .; Campbell, J . R. The Aldrich Library of 13C and 1
(
H
1.0 (8); anal. C 61.64%, H 4.83%, calcd for C
9
H
8
N
2
O
2
, C
FT NMR Spectra, 2nd ed.; Aldrich Chemical Co.: Milwaukee, 1983;
Vol. 2, p 359c.
31) Chem. Abstracts 134:252356. (b) DeGraw, J . I.; Brown, V. H.; Colwell,
W. T.; Morrison, N. E. J . Med. Chem. 1974, 17, 762-764.
32) Griefs, P. Chem. Ber. 1869, 2, 415-418.
(33) ACD NMR simulation programs Vers. 3.00; Advanced Chemistry
Development Inc.: Toronto, 1998
1.36%, H 4.58%.
4
(
,12-Dim et h yl-5H -q u in a zolin o[4,3-b]q u in a zolin e-6,8-
d ion e (11): R ) 0.52 (CHCl /10% MeOH; mp 288-290 °C;
H NMR (DMSO-d , 599.878 MHz) δ 8.32 (dd, J ) 7.6 Hz,
f
3
(
1
3
6
4
3
4
J ) 1.1 Hz, 1 H, H-11), 7.96 (dd, J ) 7.6 Hz, J ) 1 Hz, 1 H,
3
4
3
(34) Fiedler, E.; Fiedler, H. P.; Gerhard, A.; Keller-Schierlein, W.; Koenig,
W. A.; Zaehner, H. Arch. Microbiol. 1976, 107, 249-256.
H-4), 7.7 (dd, J ) 7.6, J ) 1 Hz, 1 H, H-2), 7.4 (dd, J ) 7.6,
4
3
3
J ) 1 Hz, 1 H, H-9), 7.38 (t, J ) 7.6 Hz, 1 H, H-10), 7.14 (t,
J ) 7.6 Hz, 1 H, H-3), 2.63 (s, 3 H, 1-CH ), 2.38 (s, 3 H, 8-CH );
3
3
NP0305425