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p-Bromophenacyl Derivative (15): Colorless oil; [a]D ꢂ52.1° (cꢁ1.0,
CHCl3); EI-MS: m/z 442 (Mꢀ, 3%), 309 (6), 294 (4), 228 (100), 213 (49),
185 (53), 173 (43), 145 (25), 91 (23), 77 (14), 41 (8); HR-EI-MS: m/z
442.0775 [Mꢀ], C23H23O4Br requires 442.0780; IR (KBr) cmꢂ1: 3451 (OH),
3102, 2973, 1733 (CꢁO), 1668 (CꢁO), 1632 (CꢁC), 1547, 1168; UV
(MeOH) lmax nm (log e): 256.6 (4.34), 205.2 (4.27); 1H-NMR (600 MHz) in
CDCl3 (Table 1); 13C-NMR (150 Hz) in CDCl3 (Table 2).
Biotransformation of Plagiochilide (2) by Aspergillus niger A. niger
was cultivated rotatory (100 rpm) in Czapek-pepton medium at 30 °C for 2 d.
Plagiochilide (2) (100.6 mg) was added to the medium and further cultivated
for 2 d. The cultured medium was worked up in the same manner as de-
scribed above to give EtOAc extract (75.2 mg), which was chromatographed
on silica gel (n-hexane–EtOAc gradient) to afford two new metabolites 12-
hydroxyplagiochilide (18) (44.0 mg; 40.9%) and plagiochilide-12-oic acid
(19) (11.0 mg; 12.2%). In the same condition, plagiochilide (2) (50.0 mg)
was biotransformed by A. niger for 7 d to afford the same metabolites 18
(3.1 mg; 5.8%) and 19 (42.0 mg; 74.4%).
12-Hydroxyplagiochilide (18): Colorless oil, [a]D20 ꢂ50.1° (cꢁ1.1,
CHCl3); EI-MS: m/z 248 (Mꢀ, 50%), 217 (38), 189 (26), 147 (36), 120 (94),
111 (44), 107 (100), 91 (80); HR-EI-MS: m/z 248.1416 [Mꢀ], C15H20O3 re-
quires 248.1413; IR (KBr) cmꢂ1: 3408 (OH), 2937, 1764 (CꢁO), 1178,
1112; 1H-NMR (600 MHz) in CDCl3 (Table 3): 13C-NMR (150 Hz) in CDCl3
(Table 4).
Plagiochilide-12-oic Acid (19): Colorless crystal; mp 205—206 °C; [a]D
ꢀ2.5° (cꢁ1.0, MeOH); EI-MS: m/z 262 (Mꢀ, 50%), 244 (12), 216 (17), 189
(30), 163 (39), 145 (42), 135 (39), 120 (100), 201, 175 (100 %), 173, 105,
91; HR-EI-MS: m/z 262.1191 [Mꢀ], C15H18O4 requires 262.1205; IR (KBr)
cmꢂ1: 3200—2400 (OH), 1756 (CꢁO), 1675 (CꢁO), 1110; 1H-NMR
(600 MHz) in CDCl3 (Table 3); 13C-NMR (150 Hz) in CDCl3 (Table 4).
Acetylation of Compound 18 A solution of 18 (10 mg) in pyridine
(1 ml) was treated with Ac2O (1 ml). The mixture was stirred overnight at rt.
Water was added and the mixture was extracted with CHCl3. The organic
phase was washed with 1 N HCl, 5% NaHCO3, and brine, dried (MgSO4),
and evaporated to give a residue that was purified by silica gel column chro-
matography with n-hexane–EtOAc gradient to afford 12-acetoxyplagio-
chilide (20) (11 mg, 94.1%).
12-Acetoxyplagiochilide (20): Colorless oil; [a]D20 ꢂ12.5° (cꢁ1.0,
CHCl3); EI-MS: m/z 290 (Mꢀ, 10%), 230 (20), 202 (20), 180 (24), 149 (26),
120 (67), 91 (41), 79 (28), 43 (100); HR-EI-MS: m/z 290.1521 [Mꢀ],
C17H22O4 requires 290.1518; IR (KBr) cmꢂ1: 3076, 2932, 1766 (CꢁO),
1739 (CꢁO), 1638, 1229, 1113, 1020; 1H-NMR (600 MHz) in CDCl3 (Table
3); 13C-NMR (150 Hz) in CDCl3 (Table 4).
Methylation of Compound 19 To a solution of 19 (8.5 mg) in MeOH
(3 ml) was added (CH3)3–SiCHN2 (1.0 ml). The reaction mixture was stirred
at 0—5 °C for 1 h. One drop of AcOH was added and the mixture evapo-
rated to give a residue (10.5 mg) that was purified by silica gel column chro-
matography with n-hexane–EtOAc gradient to afford 21 (4.8 mg).
Plagiochilide-12-oic Acid Methyl Ester (21): Colorless oil; [a]D ꢀ4.9°
(cꢁ0.40, CHCl3); EI-MS: m/z 276 (Mꢀ, 42), 245 (21), 216 (28), 189 (45),
145 (36), 120 (83), 107 (100), 91 (83), 80 (65), 41 (56); HR-EI-MS: m/z
276.1349 [Mꢀ], C16H20O4 requires 276.1362; IR (KBr) cmꢂ1: 2948, 2973,
1766 (CꢁO), 1719 (CꢁO), 1204, 1111, 1019; 1H-NMR (600 MHz) in
CDCl3 (Table 3).
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406—415 (1981).
Biotransformation of Plagiochilide (2) with Cytochrome P450 In-
hibitor In the same condition as described above, plagiochilide (2)
(10.0 mg) was biotransformed by A. niger with 1-aminobenzotriazole
(10.0 mg) for 7 d to give compound 18 (6.6 mg; 61.7%) together with the
substrate 2 (0.8 mg; 8.0%).
32) Based on a lecture presented at the 35th Symposium on the Chemistry
of Terpenes, Essential Oils, and Aromatics, on October 2—4, 1995,
Utsunomiya. Abstract pp. 364—366.
33) Miyazawa M., Uemura T., Tameoka H., Phytochemistry, 33, 1027—
1030 (1994).
34) Hayashi K., Asano K., Tanaka M., Takaoka D., Nozaki H., Phytochem-
istry, 48, 461—466 (1998).
35) Based on a lecture presented at the 44th Symposium on the Chemistry
of Terpenes, Essential Oils, and Aromatics, on September 15—17,
2000, Sapporo. Abstract pp. 151—153.
Acknowledgments We thank Dr. M. Tanaka, Mr. S. Takaoka, and Miss
Y. Okamoto (TBU) for providing 600 MHz NMR, X-ray crystallographic,
and mass spectra. Thanks are also due to Dr. M. Mizutani, The Hattori
Botanical Laboratory, Nichinan, Japan for identification of the liverwort and
to Miss N. Nishimatu and Miss Y. Onishi for a part of experimental works.
This work was supported in part by Grant-in-Aid for the Scientific Research
(A) (No. 11309021) from the Ministry of Education, Culture, Sports, Sci-
ence and Technology.
References and Notes
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