7
42 J ournal of Natural Products, 1996, Vol. 59, No. 8
54, and 820 cm-1; HRMS m/z 532.2259 (61, M+,
Lee and Doskotch
8
329 (4.36) nm; IR (CHCl3) ν max 3004, 2208 (CN), 1592,
C30H32N2O7, +4.9), 297.1118 (22, C18H17O4, -0.8),
66.0632 (18, C9H10O3, +0.2), 69.0582 (78, CH2dN(CN)-
1504, 1460, 1418, 1385, 1278, 1152, 1063, 1032, and 820
-
1 1
1
cm ; H-NMR (CDCl3, 90 MHz) δ 7.48 (1 H, d, J ) 8.6
Hz, H-8), 7.45 (2 H, s, H-6a and H-7), 7.30 (1 H, d, J )
8.6 Hz, H-9), 7.21 (1 H, s, H-3), 4.02 (3 H, MeO), 4.01 (3
H, MeO), 3.67 (3 H, MeO), 3.66 (3 H, MeO), 3.25-3.40
1
Me, +12.9), and 55 (100, C3H5N); and H-NMR in Table
1
.
Isola tion of Isocor yd in e. The chromatographic
fraction (133 mg) of the 1980 collection gave from Me2-
(
4 H, m, H2-4 and H2-5), and 2.84 (3 H, MeN); HRMS
+
2
5
m/z 380.1733 (88, M , C H N O , +0.3), 311.1284 (100,
CO 50 mg of colorless needles: mp 185-186 °C: [R]
D
22 24
2
4
-
5
M - CH C(Me)CN, -0.1), 279.1008 (12, M - 69 -
+
147° (c 0.3, CHCl3); CD (C 3.3 × 10 M, MeOH) (deg)
2
MeOH), 265.0848 (24, M - 69 - Me2O, +16), 69.0448
[
-
Θ]233 +279 000, [Θ]248 0, [Θ]268 -42 300, [Θ]300 (sh)
1
13
(25, CH N(Me)CN, +0.5), and 42.0345 (4, C H N, -0.1).
4800, and [Θ]320 +2500; comparison of the H- and C-
2
2
4
NMR spectra to the literature values established its
2,4,5-Tr im eth oxyben zyl a lcoh ol: prepared from
2,4,5-trimethoxybenzaldehyde (Aldrich Chemical Co.) by
identity.3
0,31
3
3
34
NaBH4 reduction; mp 72-74 °C from Et2O (lit. mp
O-Meth ylisocor yd in e (O,O-Dim eth ylcor ytu ber -
cin e). Isocorydine (20 mg) in 1.0 mL of MeOH was
treated with 12 mL of 1.5% CH2N2 in Et2O for 4 days
at 4 °C. The residue after solvent removal was purified
by preparative TLC on basic Al2O3 (0.5 mm) with Et2O-
PhH (1:1), and two developments, followed by chroma-
tography on a Si gel (3 g) column with 0.5% (50 mL)
and 2% (40 mL) MeOH in CHCl3. The amorphous
1
7
6
4
0°); H NMR (CDCl3, 500 MHz) δ 6.85 (1 H, s, H-6),
.52 (1 H, s, H-3), 4.60 (2 H, s, CH2), 3.87 (3 H, s, MeO-
), 3.82 (6 H, s, MeO-2 and MeO-5), and 2.33 (1 H, br s,
1
3
OH); C NMR (CDCl3, 125 MHz) δ 151.8 (s, C-2), 149.3
(s, C-4), 143.1 (s, C-5), 120.9 (s, C-1), 113.5 (d, C-6), 97.6
(d, C-3), 61.5 (t, CH2), 56.8 (q, MeO-2 or MeO-5), 56.4
(q, MeO-4), 56.3 (q, MeO-2 or MeO-5). The NMR
product gave [R]25D +222° (c 1.0, CHCl3) and H-NMR
1
32
assignments were made from NOED, DEPT, CH-cor-
relation, and COLOC studies.
(
CDCl3, 500 MHz) δ 6.95 (1 H, d, J ) 8.1 Hz, H-8), 6.84
1 H, d, J ) 8.1 Hz, H-9), 6.66 (1 H, s, H-3), 3.88 (3 H,
(
Ack n ow led gm en t. We thank Dr. C.E. Cottrell for
the NMR spectra at 500 MHz and Mr. C.R. Weisen-
berger and Mr. D. Chang for the mass spectra obtained
at The Ohio State Univeristy Chemical Instrument
Center. The FT-NMR spectra at 11.75 T (500 MHz)
were obtained at the center using equipment funded in
part by NIH Grant no. 1-510RR0145-01A1.
s, MeO-10), 3.87 (3 H, s, MeO-2), 3.72 (3 H, s, MeO-1 or
MeO-11), 3.64 (3 H, s, MeO-11 or MeO-1), 3.16 (1 H,
ddd, J ) 15.7, 12.3, 6.0 Hz, H-4â), 3.03 (1 H, dd, J )
1
2
1
1.6, 6.4 Hz, H-5â), 3.01 (1 H, J ) 13.5, 3.4 Hz, H-7R),
.89 (1 H, br d, J ) 11.3 Hz, H-6a), 2.69 (1 H, dd, J )
6.4, 3.6 Hz, H-4R), 2.53 (1 H, hm, H-5R), 2.54 (3 H, s,
MeN), and 2.38 (1 H, dd, J ) 13.0, 13.0 Hz, H-7â).
Br CN Tr ea tm en t of Acetylisocor yd in e. The ac-
Refer en ces a n d Notes
etate derivative was prepared from 49 mg of isocorydine,
(
1) Alkaloids of Thalictrum 36. Paper 35 is Wu, W.-N.; Beal, J . L.;
Doskotch, R. W. J . Nat. Prod. 1980, 43, 567-570 This study is
taken in part from the Ph.D. dissertation of S. S. Lee as accepted
by the Graduate School, The Ohio State University, December
3
mL of Ac2O, and 1 mL of pyridine at room temperature
overnight. The clean product (Ac at 2.24 ppm in CDCl3
at 90 MHz) was dissolved in 3 mL of CHCl3 and stirred
magnetically with 44 mg of BrCN in 2 mL of CHCl3 for
1
985.
(2) Li, H.-L.; Liu, T.-S.; Huang, T.-C.; Koyama, T.; DeVol, C. E. Flora
of Taiwan; Epoch Publishing: Taipei, R.O.C., 1976; Vol. 2, p 510.
4
h under N2. After workup as given for faurine (1), 16
(3) Chen, C.-H.; Wu, J . Taiwan Yao Hsueh Tsa Chih. 1976, 28, 121-
mg of the phenanthrene product 7 was obtained show-
124.
2
5
-5
(4) Chen, C.-H.; Chen, T.-M.; Lee, C. J . Pharm. Sci. 1980, 69, 1061-
ing: [R] D +2° (c 0.5, MeOH); CD (C 2.7 × 10 M,
1
065.
MeOH) (deg) [Θ]222 0, [Θ]235 +10 390, and [Θ]243 0; UV
MeOH) λ max (log ꢀ) 240 sh (4.60), 258 (4.79), 297 sh
4.14), 311 (4.35), and 323 (4.37) nm; IR (CHCl3 ν max
(
5) Chen, C.-H. Saengyak Hakhoechi 1986, 17, 49-54.
(
(
(6) Cava, M. P.; Bessho, K.; Douglas, B.; Markey, S.; Weisbach, J .
A. Tetrahedron Lett. 1966, 4279-4282.
(7) Liao, W.-T.; Beal, J . L.; Wu, W.-N.; Doskotch, R. W. Lloydia 1978,
3
1
010, 2220 (CN), 1768 (CdO), 1608, 1595, 1463, 1431,
289, 1197, 1156, 1064, 1023, and 825 cm ; H-NMR
4
1, 271-276.
-
1 1
(8) Hussain, S. F.; Fajardo, V.; Shamma, M. J . Nat. Prod. 1989,
5
2, 644-645.
(
(
300 MHz, CDCl3) δ 7.70 (1 H, d, J ) 8.7 Hz, H-8), 7.50
1 H, d, J ) 9.0 Hz, H-6R), 7.47 (1 H, d, J ) 9.0 Hz,
(
9) Nabih, T.; Davis, P. J .; Caputo, J . F.; Rosazza, J . P. J . Med.
Chem. 1977, 20, 914-917.
(
(
(
10) Hussain, S.; Siddiqui, M. T.; Manikumar, G.; Shamma, M.
Tetrahedron Lett. 1980, 723-726.
H-7), 7.37 (1 H, d, J ) 8.7 Hz, H-9), 7.26 (1 H, s, H-3),
.04 (3 H, s, MeO-2), 3.96 (3 H, s, MeO-10), 3.42 (3 H,
s, MeO-1), 3.40 (2 H, m, H2-4), 3.29 (2 H, m, H2-5), 2.84
3 H, s, MeN-6), and 2.38 (3 H, s, AcO-11); NOED (300
4
11) Fajardo, V.; Guinaudeau, H.; Elango, V.; Shamma, M. J . Chem.
Soc., Chem. Commun. 1982, 1350-1352.
12) Lin, L.-Z.; Wagner, H.; Seligmann, O. Planta Med. 1983, 49, 55-
(
5
6.
MHz, CDCl3) δ 7.70 (H-8) relaxed to 7.47 (H-7, 12%)
and 7.37 (H-9, 17%), 4.04 (MeO-2) relaxed to 7.26 (H-3,
(13) Wu, W.-N.; Beal, J . L.; Mitscher, L. A.; Salman, K. N.; Patil, P.
Lloydia 1976, 39, 204-212.
(
(
14) Shamma, M.; Slusarchyk, W. A. Chem. Revs. 1964, 64, 59-79.
15) The methylated product of faurine, although not characterized,
1
4%), 3.96 (MeO-10) relaxed to 7.37 (H-9, 17%), and 2.84
1
(
MeN-6) relaxed to 3.29 (H2-5, 1%); HRMS m/z 408.1653
showed in the H-NMR spectrum eight methyl peaks, and its
+
TLC mobility was that of a quaternary alkaloid.
16) Tomita, M.; Takano, Y. Yakugaku Zasshi 1960, 80, 1645-1647.
17) Smissman, E. S.; Makriyannis, A. C.; Walascek, E. J . J . Med.
Chem. 1970, 13, 640-644.
(7, M , C23H24N2O5, -3.2), 366.1524 (26, M - C2H2O,
(
(
C21H22N2O4, -5.6) 297.1091 (23, M - C2H2O - C3H5N2,
C18H17O4, -3.5), 69.0684 (100, CH2N(Me)CN, +12.0),
(
18) Hageman, H. A. In Organic Reactions; Adams R., Ed.; J ohn
4
3.9922 (20, CO2, +2.4), and 43.0194 (23, CH3CO, +1.0).
Wiley: New York, 1953; Vol. 7, pp 198-262.
Br CN Tr ea tm en t of O-Meth ylisocor yd in e. O-
(19) J affe, H. H.; Orchin, M. Theory and Applications of Ultraviolet
Spectroscopy; J ohn Wiley: New York, 1962; p 323.
20) The aporphine numbering system is retained in the phenan-
Methylisocorydine (20 mg) in 3 mL of CHCl3 was treated
with 20 mg of BrCN in 2 mL of CHCl3 as described for
acetylisocorydine to give 8 mg of phenanthrene 8:
optically inactive ([R]D, CD); UV (MeOH) λ max (log ꢀ)
(
threne for easy reference.
(
(
(
21) Shamma, M. Experientia 1960, 16, 484-485.
22) Craig, J . C.; Roy, S. K. Tetrahedron 1965, 21, 345-399.
23) Djerassi, C.; Mislow, K.; Shamma, M. Experientia 1962, 18, 53-
56.
2
45 sh (4.56), 264 (4.82), 302 sh (4.21), 318 (4.33), and