Efficient synthesis of fused bicyclic glutarimides. Its application to (±)-alloyohimbane and louisianin D

Article abstract of DOI:10.1021/ol060958k

The reaction of α-sulfonyl acetamide 1 with various cyclic unsaturated esters 2 to fused bicyclic glutarimides is reported. Syntheses of (±)-alloyohimbane (4) and louisianin D (5) have been accomplished.

Full text of DOI:10.1021/ol060958k

ORGANIC
LETTERS
2006
Vol. 8, No. 14
3033-3035
Efficient Synthesis of Fused Bicyclic
Glutarimides. Its Application to
(±)-Alloyohimbane and Louisianin D
Hung-Wei Chen,† Ru-Ting Hsu,‡ Meng-Yang Chang,§ and Nein-Chen Chang*,†
Department of Chemistry, National Sun Yat-Sen UniVersity, Kaohsiung 804, Taiwan,
Department of Nursing, Shu-Zen College of Medicine and Management,
Kaohsiung County 821, Taiwan, and Department of Applied Chemistry,
National UniVersity of Kaohsiung, Kaohsuing 804, Taiwan
ncchang@mail.nsysu.edu.tw
Received April 21, 2006
ABSTRACT
The reaction of
r-sulfonyl acetamide 1 with various cyclic unsaturated esters 2 to fused bicyclic glutarimides is reported. Syntheses of
(
±
)-alloyohimbane (4) and louisianin D (5) have been accomplished.
Bicyclic pyridines, piperidines, δ-lactams, and 2-pyridones
are important core structures that are found in numerous
biologically active compounds.1 Although many methods
have been reported for the synthesis of such compounds,2
we envisioned that our previously developed [3+3] annu-
lation of R-sulfonyl acetamide with R,â-unsaturated esters
to give polysubstituted glutarimides3 would be ideal for
constructing fused bicyclic glutarimides which could be
further converted to nitrogen-containing polycyclic alkaloids.2b,4
Thus, the reaction of R-sulfonyl acetamide 1 with various
cyclic unsaturated esters 2 was investigated. The results are
shown in Table 1. It is interesting to note that 3a and 3b are
both cis-fused bicyclic compounds. The structures of 3a and
3b were unequivocally established by single-crystal X-ray
(2) For pyridines, see: (a) Jones, K.; Escudero-Hernandez, M. L.
Tetahedron 1998, 54, 2275. (b) John, K.; Fiumana, A.; Escudero-Hernandez,
M. L. Tetrahedron 2000, 56, 397. For piperidines, see: (c) Hong, B.-C.;
Gupta, A. K.; Wu, M.-F.; Liao, J.-H.; Lee, G.-H. Org. Lett. 2003, 5, 1689.
(d) Gunter, M.; Gais, H.-J. J. Org. Chem. 2003, 68, 8037. For δ-lactams,
see: (e) Li, T.-T.; Lesko, P.; Ellison, R. H.; Subramanian, N.; Fried, J. H.
J. Org. Chem. 1981, 46, 111. (f) Gracias, V.; Frank, K. E.; Milligan, G. L.;
Aube, J. Tetrahedron 1997, 48, 16241. For 2-pyridones, see: (g) Yamamoto,
Y.; Takagish, H.; Itoh, K. Org. Lett. 2001, 3, 2117.
(3) Chang, M.-Y.; Chang, B.-R.; Tai, H.-M.; Chang, N.-C. Tetahedron
Lett. 2000, 41, 10273.
(4) (a) Bergmeier, S. C.; Seth, P. P. J. Org. Chem. 1999, 64, 3237. (b)
Beierle, J. M.; Osimboni, E. B.; Metallinos, C.; Zhao, Y.; Kelly, T. R. J.
Org. Chem. 2003, 68, 4970. (c) Kogure, N.; Nishiya, C.; Kitajima, M.;
Takayama, H. Tetahedron Lett. 2005, 46, 5857.
† National Sun Yat-Sen University.
‡ Shu-Zen College of Medicine and Management.
§ National University of Kaohsiung.
(1) (a) Frederlesen, S. M.; Stermitz, F. R. J. Nat. Prod. 1996, 59, 41.
(b) Stefanska, A. L.; Cassel, R.; Ready, S. J.; Warr, S. R. J. Antibiot. 2000,
53, 357. (c) Nakamura, M.; Kido, K.; Kinjo, J.; Nohara, T. Phytochemistry
2000, 53, 253. (d) Nakamura, M.; Chi, Y.-M.; Yan, W.-M.; Yonezawa, A.;
Nakagugi, Y.; Toyokichi, Y.; Hashimoto, F.; Kinjo, J.; Nohara, T.; Sakurada,
S. Planta Med. 2001, 67, 114. (e) Skaltsounis, A.-L.; Michel, S.; Tillequin,
F.; Koch, M.; Pusset, J.; Chauviere, G. HelV. Chim. Acta 1985, 68, 1679.
(f) Cook, C. E.; Wani, M. C.; Jump, J. M.; Jee, Y. M.; Fail, P. A. J. Med.
Chem. 1995, 38, 753. (g) Ho, H. Y.; Chow, Y. S. J. Chem. Ecol. 1993, 19,
39. (h) Torsell, K.; Wahlberg, K. Acta Chem. Scand. 1967, 21, 53. (i) Scott,
J. A.; Crews, F. T. J. Pharmacol. Exp. Ther. 1983, 224, 640.
10.1021/ol060958k CCC: $33.50
© 2006 American Chemical Society
Published on Web 06/13/2006

Table 1. Formation of Fused Bicyclic Glutarimides
Figure 1. X-ray structures of (()-3a and (()-3b.
starting material. Following the procedure developed in our
laboratory,7 3a was reduced regioselectively to the corre-
sponding hydroxylactam 8. Treatment of 8 with boron
triflouride furnished enlactam 9. Allylation of 9 followed
by dehydrosulfonation produced double-bond migrated 2-py-
ridone 10. To accomplish the synthesis of louisianin D, 10
was first converted to the corresponding 2-chloropyridine
11, which was then reduced to bicyclic pyridine 12 by
treatment of 11 with zinc in acetic acid.8 Regioselective
hydroxylation of 12 with LHMDS and oxygen yielded 13,9
which was then further oxidized with the swern-oxidation
a All yields were based on R-toluenesulfonyl acetamide.
analysis (Figure 1). The stereochemistries of 3c-e were
determined by comparing their 1H NMR spectra with those
of 3a and 3b.
To demonstrate the utility of this one-pot process, the
formal synthesis of (()-alloyohimbane (4) was investigated.
As shown in Scheme 1, regioselective reduction of 3e by
sequential addition of triethylamine in THF and LAH
reduction at refluxing temperature furnished 6. Treatment
of 6 with sodium amalgam gave 4,5-annulated lactam 7. The
spectral data of 7 were in agreement with those reported in
the literature.4a Lactam 7 has been converted to alloyohim-
bane (4).4a,5 Thus, the formal synthesis of alloyohimbane (4)
was accomplished.
Scheme 1. Formal Synthesis of (()-Alloyohimbane
For the synthesis of louisianin D (5)4b produced by a
species of Streptomyces,6 glutarimide 3a was chosen as the
(5) (a) Sparks, S. M.; Shea, K. J. Tetahedron Lett. 2000, 41, 6721. (b)
Aube, J.; Wang, Y. G.; Hammond, M.; Tanol, M.; Takusagawa, F.;
Vandervelde, D. J. J. Am. Chem. Soc. 1990, 112, 4879.
(6) Takamatsu, S.; Kim, Y.-P.; Hayashi, M.; Furuhata, K.; Takayanagi,
H.; Komiyama, K.; Woodruff, H. B.; Omura, S. J. Antibiot. 1995, 48, 1090.
(7) Chang, B.-R.; Chen, C.-Y.; Chang, N.-C. Tetrahedron Lett. 2002,
43, 3233.
(8) Pampin, M. C.; Estevez, J. C.; Estevez, R. J.; Maestro, M.; Castedo,
L. Tetrahedron 2003, 59, 7231.
3034
Org. Lett., Vol. 8, No. 14, 2006

In conclusion, we have developed a one-pot reaction
procedure to cis-fused bicyclic glutarimides. Syntheses of
(()-alloyohimbane (4) and louisianin D (5) were reported.
Further application of fused bicyclic glutarimides to more
complicated pentacyclic indole alkaloids is underway in our
laboratory.
Scheme 2. Total Synthesis of Louisianin D
Acknowledgment. Financial support from the National
Science Council of the Republic of China is gratefully
acknowledged.
Supporting Information Available: Additional spectro-
scopic data for all new compounds (1H NMR in CDCl3) and
X-ray crystallographic data in CIF format. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL060958K
(9) (a) Boch, M.; Korth, T.; Nelke, J. M.; Pike, D.; Radunz, H.;
Winterfeldt, E. Chem. Ber. 1972, 105, 2126. (b) Tang, C. S. F.; Morrow,
C. J.; Rapoport, H. J. Am. Chem. Soc. 1975, 97, 159. (c) Shen, W.; Coburn,
C. A.; Bornmann, W. G.; Danishefsky, S. J. J. Org. Chem. 1993, 58, 611.
(d) Ragan, J. A.; Jones, B. P.; Meltz, C. N.; Teixeira, J. J., Jr. Sythesis
2002, 4, 483. (e) Stork, G.; Fujimoto, D. N. A.; Koft, E. R.; Balkovec, J.
M.; Tata, J. R.; Dake, G. R. J. Am. Chem. Soc. 2001, 123, 3239.
reagent to afford 5 (Scheme 2). The spectral data of 5 were
in agreement with those reported in the literature.6
Org. Lett., Vol. 8, No. 14, 2006
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