Structure
Name
Alstonisine
O
H
H
Reference
O
H
N
Org. Lett. 2002, 4, 4237-4240
Xiangyu Z. Wearing and James M. Cook*
H
Department of Chemistry, UniVersity
of Wisconsin-Milwaukee,
Milwaukee, Wisconsin
H
N
O
CH3
Abstracted by
11
Eric Korf
In 1972 Elderfield and Gilman reported the isolation of the first macroline-related oxindole alkaloid from
Alstonia muelleriana Domin and termed it alstonisine (11).1 Since this initial report, alstonisine (11) has also
been isolated from Alstonia angustifolia Wall2 and Alstonia macrophylla.3 The original structure and relative
configuration of this alkaloid were established through single-crystal X-ray analysis by Nordman.4 The total
synthesis of alstonisine was accomplishedin enantiospecific fashion in an overall yield of 12%
(fromtryptophan methyl ester) in 17 reaction vessels. The structureof alstonisine (11) has been determined
by NOE spectroscopicexperiments and was confirmed by single-crystal X-ray analysis.
Retro
O
H
O
H
N
H
H
Bn
N
H
CH3
H
N
O
CH3
11
H
H
OCH3
H
CO2H
Bn
N
H
3
H
N
H
CH3
H
O
N
H
7
O
H
NH2
D-(+)-tryptophan
Bn
O
N
9
H
N
H
H
N
H
O
H
Bn
N
N
H
CH3
H
12
(1) Elderfield, R. C.; Gilman, R. E. Phytochemistry 1972, 11, 339.
(2) Ghedira, K.; Zeches-Hanrot, M.; Richard, B.; Massiot, G.; Le Men- Oliver, L.; Sevenet, T.; Goh, S. H.
Phytochemistry 1988, 27, 3955.
(3) Wong, W. H.; Lim, P. B.; Chuah, C. H. Phytochemistry 1996, 41,313.
(4) Nordman, C. E.; Nakatsu, K. J. Am. Chem. Soc. 1963, 85, 353. Phytochemistry 1987, 26, 865.
O
Scheme 1 Taken from J. Org. Chem. 1998, 63, 9190
H
CO2Me a. PhCHO/CH3OH, rt, 2 h
NH2
N
H
b. NaBH4, -5 °C
c. TFA, (2.4 equiv)/
CH2Cl2/(CH3O)2CHCH2CO2Me
rflx, 12 h 83%
1
H
Bn
N
H
N
CO2Me
3
CO2Me
2
H
O a. ClCH2SOPh/LDA/THF, -78 °C
Bn
b. KOH, 6 h
c. LiClO4/dioxane/rflx, 10 h 87%
H
NH
N
H
N
H
CH3
O
a. NaH (8 equiv)/CH3OH
rflx, 48 h
b. HOAc/HCl/H2O/rflx,
10 h, 80%
Li/biphenyl/THF dry BaI2 -78
°C 5 h, 90%
N
Br
4
H
1. KH/dioxane/18-crown-6/rflx 14 h then MeOH 85%
OH
HN
Bn
N
H
CH3
2. NaH (1.1 equiv)/THF/MeI, rt, 6 h 95%
3. NaBH4/MeOH, rt, 1h 96%
Bn N
H
OH
N
H
6
5
H
1. OsO4/THF/py, NaHSO3, NaIO4,
H2O, MeOH, 0 °C, 3 h, 78%
Bn
N
H
CH3
2. Benzene/TSA/DST, rflx, 5 h, 95%
H
O
N
H
7
Scheme 2
O
N SePh
7
H
O
1. TSA/ CH2Cl2-MeOH
Bn
N
N
H
CH3
H
8
2. NaIO4/H2O/THF/MeOH 0°C 10 h, 90%
H
Bn
N
H
CH3
1. BH3 THF, 0°C 14 h, 85%
O
OCH3 2. Swern, 80%
O
H
O
N
OCH3
H
9
H
1. 1 eq OsO4/py THF, rt, 3 d
aq. NaHSO3, rt, 4 h, 81%
H
H
O
N
Bn
O
N
CH3
1. 2 eq. Pd(OH)2/C, EtOH, H2, rt, 5 h
2. 2N NaOH/MeOH, rt, 2 h, 86% 2 steps
11
OCH3
O
H
H
10