1136
H. Tani et al. / Phytochemistry 62 (2003) 1133–1140
with a JEOL JNM-ECP 500 NMR spectrometer. Che-
mical shifts were referenced to CDCl3 (ꢀH 7.26, ꢀC 77.0).
Mass spectra were obtained with a JEOL AX505HA
spectrometer (direct probe) and glycerol was the matrix
used for FABMS. In EIMS the ionization voltage was
70 eV, and in CIMS the reaction gas was iso-butane.
HPLC was carried out with a Cosmosil 5C18-AR col-
umn (Nacalai Tesque, 10ꢁ250 mm), a flow rate of 1.0
ml/min, and detection at 220 nm. Daisogel IR-60 was
used for silica gel column chromatography and Merck
Kieselgel 60 F254 for TLC.
26.5, 28.8, 29.1, 33.1, 35.8, 47.0, 53.4, 54.4, 57.8, 58.8,
70.9, 76.1, 126.7, 128.6, 129.0, 137.0, 171.9, 172.8, 174.4,
175.6. EIMS m/z (rel. int.): 530 [M]+ (11), 486 (12), 485
(20), 430 (24), 412 (11), 411 (15), 332 (20), 314 (11), 229
(25), 120 (35), 70 (100), 69 (12), 58 (64), 57 (11), 55 (15).
3.3. Compound 4a
A soln of 4 (3.2 mg, 0.0060 mmol) was dissolved in
2,2-dimethoxypropane (1.0 ml) and a catalytic amount
of p-toluenesulfonic acid was added and stirred for 30
min at room temp., and the solvent was then evaporated
in vacuo. The residue was purified by silica gel column
chromatography to give 4a (2.4 mg, 0.0042 mmol, 70%)
as a colorless oil. 1H NMR (500 MHz, CDCl3): ada ꢀ 1.13
(3H, d, J =6.2 Hz, H-10), 1.23–1.85 (10H, m, H-3-7), 1.33
(3H, s, CH3C), 1.44 (3H, s, CH3C), 4.01 (1H, m, H-8), 4.22
(1H, dq, J =7.3, 6.2 Hz, H-9), 4.18 (1H, ddd, J =7.6, 7.6,
10.1 Hz, H-2), 7.08 (1H, d, J =10.1 Hz, NH), aib ꢀ 1.34
(3H, s, H-4), 1.77 (3H, s, H-3), 5.89 (1H, s, NH), Phe ꢀ 2.95
(1H, dd, J =5.7, 13.8 Hz, H-3), 3.26 (1H, dd, J =10.1, 13.8
Hz, H-3), 5.16 (1H, ddd, J =5.7, 10.1, 10.1 Hz, H-2), 7.19–
7.29 (5H, m, H-5-9), 7.52 (1H, d, J =10.1 Hz, NH), Pro ꢀ
1.23–1.85 (2H, m, H-3 and 4), 2.12–2.35 (2H, m, H-3 and
4), 3.22 (1H, ddd, J =7.6, 7.6, 10.1 Hz, H-5), 3.86 (1H, ddd,
J =4.2, 8.3, 9.6 Hz, H-5), 4.66 (1H, dd, J =2.2, 7.6 Hz, H-
2). EIMS m/z (rel. int.): 570 [M]+ (36), 556 (23), 555 (49),
513 (20), 485 (26), 470 (26), 455 (23), 451 (21), 412 (35), 314
(21), 229 (26), 120 (34), 70 (100), 58 (70).
3.2. Compounds 4 and 5
A soln of 1 (25.6 mg, 0.048 mmol) and NaBH4 (3.0
mg, 0.072 mmol) in dry MeOH (1.0 ml) was stirred for
15 min at room temp. The reaction mixture was diluted
with 15 ml of brine (pH 2.0 with HCl), and the products
were extracted with EtOAc (15 mlꢁ3). The EtOAc
extract was dried over Na2SO4 and evaporated in
vacuo. The residue was purified by HPLC (70% MeOH)
to give 4 (8.0 mg, 0.015 mmol, 31%, Rt 19.2 min) and 5
(11.5 mg, 0.022 mmol, 46%, Rt 20.5 min) as colorless
ꢃ
1
oils. 4: [ꢁ]2D5 ꢂ49 (c 0.10; EtOH). H NMR (500 MHz,
CDCl3): l-a-aminodecanoic acid (ada) ꢀ 1.15 (3H, d, J
=6.5 Hz, H-10), 1.25-1.84 (10H, m, H-3-7), 3.60 (1H,
m, H-8), 3.78 (1H, dq, J =3.5, 6.5, H-9), 4.19 (1H, ddd,
J =7.6, 7.8, 10.1 Hz, H-2), 7.11 (1H, d, J =10.1 Hz,
NH), a-aminoisobutyric acid (aib) ꢀ 1.34 (3H, s, H-4),
1.77 (3H, s, H-3), 5.97 (1H, s, NH), Phe d 2.95 (1H, dd,
J =5.8, 13.5 Hz, H-3), 3.26 (1H, dd, J =10.1, 13.5 Hz,
H-3), 5.16 (1H, ddd, J =5.8, 10.1, 10.1 Hz, H-2), 7.19-
7.29 (5H, m, H-5-9), 7.51 (1H, d, J =10.1 Hz, NH), Pro
ꢀ 1.25–1.84 (2H, m, H-3 and 4), 2.14–2.34 (2H, m, H-3
and 4), 3.22 (1H, ddd, J =7.6, 7.6, 10.1 Hz, H-5), 3.86
(1H, ddd, J =4.4, 8.3, 10.1 Hz, H-5), 4.66 (1H, dd, J
=2.3, 8.1 Hz, H-2). 13C NMR (125 MHz, CDCl3):
ꢀ16.7, 23.6, 24.7, 25.0, 25.3, 25.6, 26.5, 28.8, 29.1, 31.5,
35.8, 47.0, 53.4, 54.4, 57.8, 58.8, 70.4, 74.8, 126.7, 128.6,
129.0, 137.0, 171.9, 172.8, 174.4, 175.6. EIMS m/z (rel.
int.): 530 [M]+ (11), 485 (17), 412 (14), 411 (13), 332
(12), 314 (13), 230 (11), 229 (26), 120 (32), 70 (100), 69
3.4. Compound 5a
Compound 5 (8.0 mg, 0.015 mmol) was treated with
2,2-dimethoxypropane and p-toluenesulfonic acid under
the same conditions as 4 to give 5a (5.0 mg, 0.0088
1
mmol, 59%) as a colorless oil. H NMR (500 MHz,
CDCl3): ada ꢀ 1.24 (3H, d, J =6.0 Hz, H-10), 1.26–1.86
(10H, m, H-3-7), 1.38 (3H, s, CH3C), 1.39 (3H, s,
CH3C), 3.49 (1H, m, H-8), 3.69 (1H, dq, J =8.0, 6.0 Hz,
H-9), 4.18 (1H, ddd, J =7.8, 7.8, 10.1 Hz, H-2), 7.08
(1H, d, J =10.1 Hz, NH), aib ꢀ 1.34 (3H, s, H-4), 1.77
(3H, s, H-3), 5.87 (1H, s, NH), Phe ꢀ 2.95 (1H, dd, J
=5.7, 13.5 Hz, H-3), 3.26 (1H, dd, J =10.1, 13.5 Hz, H-
3), 5.16 (1H, ddd, J =5.7, 10.1, 10.1 Hz, H-2), 7.19–7.30
(5H, m, H-5-9), 7.50 (1H, d, J =10.1 Hz, NH), Pro ꢀ
1.26–1.90 (2H, m, H-3 and 4), 2.13–2.36 (2H, m, H-3
and 4), 3.22 (1H, ddd, J =7.4, 7.5, 10.0 Hz, H-5), 3.86
(1H, ddd, J =4.6, 8.5, 10.1 Hz, H-5), 4.66 (1H, dd, J =2.3,
7.8 Hz, H-2). EIMS m/z (rel. int.): 570 [M]+ (16), 556 (9),
555 (29), 513 (11), 485 (14), 470 (14), 455 (13), 451 (13), 412
(19), 314 (14), 229 (18), 120 (27), 70 (100), 58 (75).
(11), 58 (66). 5: [ꢁ]2D5 ꢂ48ꢃ (c 0.15; EtOH). H NMR
1
(500 MHz, CDCl3): ada ꢀ 1.19 (3H, d, J =6.2 Hz, H-
10), 1.24–1.90 (10H, m, H-3-7), 3.32 (1H, m, H-8), 3.59
(1H, dq, J =6.4, 6.2 Hz, H-9), 4.19 (1H, ddd, J =7.6,
7.6, 10.1 Hz, H-2), 7.12 (1H, d, J =10.1 Hz, NH), aib ꢀ
1.34 (3H, s, H-4), 1.77 (3H, s, H-3), 6.02 (1H, s, NH),
Phe ꢀ 2.95 (1H, dd, J =5.8, 13.5 Hz, H-3), 3.26 (1H, dd,
J =10.1, 13.5 Hz, H-3), 5.16 (1H, J =ddd, 5.8, 10.1,
10.1 Hz, H-2), 7.19–7.29 (5H, m, H-5-9), 7.51 (1H, d, J
=10.1 Hz, NH), Pro ꢀ 1.24–1.90 (2H, m, H-3 and 4),
2.12–2.35 (2H, m, H-3 and 4), 3.21 (1H, ddd, J =7.6,
7.6, 10.1 Hz, H-5), 3.86 (1H, ddd, J =4.1, 8.3, 10.1 Hz,
H-5), 4.66 (1H, dd, J =2.3, 8.0 Hz, H-2). 13C NMR
(125 MHz, CDCl3): ꢀ 19.5, 23.6, 24.7, 25.0, 25.2, 25.3,
3.5. Compound 6
A mixture of 4 and 5 (39.6 mg, 0.075 mmol) in MeOH
(2.0 ml) was added to a soln of NaIO4 (19.3 mg) in H2O