6
752
M. Yoshida et al. / Tetrahedron Letters 43 (2002) 6751–6753
Reduction of 9 with NaBH CN in the presence of
indicated the cis-orientation between the 4b-amine
function and the 10b-hydroxyl group. It was found
that selective deoxygenation of the 10b-oxygen func-
tion and reductive N-methylation concomitantly
occurred when the cyclic carbamate 14 was treated
3
8
TiCl3 successfully provided an amine 6 as the desired
single stereoisomer. Reductive cleavage of the spiro-
lactone ring in 6 with LiAlH followed by cyclization
4
under the Mitsunobu reaction conditions after conver-
sion of the reduction product 10 into a trifluoroac-
etamide derivative 11 gave a 10b,11,12-trioxygenated
hexahydrobenzo[c]phenanthridine skeleton 12. All cis
relation among the hetero atom substituents on the C
ring system of 12 was determined by NOE enhance-
ments in NMR experiments.
with 20% Pd(OH) /C under hydrogen atmosphere in
2
the presence of formaldehyde, to directly give an
1
1,12-dioxygenated
hexahydro-N-methylbenzo[c]-
phenanthridine skeleton 5 with all cis-oriented hydro-
gen atoms on the C ring. Interestingly, reductive
inversion at the 10b-position by displacement of an
oxygen function to a hydrogen atom was observed in
this reduction, resulting in the formation of a product
with the desired stereochemistry. After deprotection
of the acetal function in 5 followed by thiocarbama-
Hydrolysis of the amide function of 12 followed by
treatment with Boc O afforded an unexpected cyclic
2
carbamate 14 quantitatively. This fact unambiguously
tion, treatment of the thiocarbamate 16 under radical
9
conditions using Bu SnH smoothly afforded the
3
expected homochelidonine (1), which was identical
3b
with an authentic sample (Scheme 2). The overall
yield of 1 from 3 was 11% in 15 steps.
In conclusion, (±)-homochelidonine (1) was stereose-
lectively synthesized from arnottin II (3) through
three key steps of (i) the introduction of oxygen func-
tions to the 11 and 12 positions, (ii) reduction of the
oxime group, and (iii) hydrogenolysis of the 10b-
hydroxyl group. It should be noted that synthetic cor-
relation among homochelidonine (1) (a partially
hydrogenated-type alkaloid), chelerythrine (2) (a fully
aromatized-type alkaloid), and arnottin II (3) (a non-
alkaloidal spirolactonyl tetralone) in the use of the
2
-benzofuranyl-1-tetralone (4) as a common key inter-
mediate could propose a valuable synthetic method
accessible to both types of alkaloids. Presently, opti-
mization of each step and trials for application to
asymmetric synthesis are under investigation.
Acknowledgements
We thank Professor T. Naito of Kobe Pharmaceutical
University for a generous gift of the authentic sample
of homochelidonine.
References
1
2
. Simanek, V. In The Alkaloids; Brossi, A., Ed.; Academic
Press: New York, 1983; Vol. 26, p. 185.
. Ishikawa, T.; Ishii, H. Heterocycles 1999, 50, 627–639.
Scheme 2. (a) (i) OsO , pyridine, rt, 1 h; (ii) NaHSO3 aq.,
3. For example: (a) Oppolzer, W.; Keller, K. J. Am. Chem.
Soc. 1971, 93, 3836–3837; (b) Ninomiya, I.; Yamamoto,
O.; Naito, T. J. Chem. Soc., Perkin Trans. 1 1983, 2171–
2174.
4
rt, 20 h; (b) (CH ) C(OCH ) , p-TsOH·H O, DMF, 90°C, 1
3
2
3 2
2
h; (c) NH OH·HCl, pyridine, 100°C, 6 h; (d) TiCl3 aq.,
2
NaBH CN, NH OAc, dioxane, rt, 5 h; (e) LiAlH , THF, rt,
3
4
4
1
h; (f) (i) (CF CO) O, pyridine, 0°C, 2 h; (ii) NaHCO aq.,
4. (a) Ishii, H.; Ichikawa, Y.-I.; Kawanabe, E.; Ishikawa,
M.; Ishikawa, T.; Kuretani, K.; Inomata, M.; Hoshi, A.
Chem. Pharm. Bull. 1985, 33, 4139–4151; (b) Ishii, H.;
Chen, I.-S.; Ishikawa, T. J. Chem. Soc., Perkin Trans. 1
1987, 671–678; (c) Ishii, H.; Chen, I.-S.; Ueki, S.;
Akaike, M.; Ishikawa, T. Chem. Pharm. Bull. 1987, 35,
2717–2725.
3
2
3
MeOH, rt, 16 h; (g) DEAD, Ph P, THF, rt, 3 h; (h) NaOH
aq., MeOH, rt, 24 h; (i) Boc O, DMAP, CH CN, 60°C, 2
h; (j) H , 20% Pd(OH) /C, HCHO aq., HCOOH, MeOH,
rt, 24 h; (k) CF COOH, CH Cl , rt, 20 h; (l) thiocar-
bonyldiimidazole, (CH Cl) , reflux, 3 h; (m) Bu SnH, AlBN,
toluene, reflux, 3 h.
3
2
3
2
2
3
2
2
2
2
3
Yoshida, Makoto
