138
LETTERS
SYNLETT
With these results in hand, the total synthesis of (+)-4 was accomplished
in a short number of steps as follows: Nucleophilic addition of
(3) (a) Elbein, A. D.; Molyneux, R. J. In Alkaloids: Chemical and
Biological Perspectives; Pelletier, S. W.; Ed.; Wiley: New York,
1987; Vol. 5, Chapter 1, pp.1. (b) Howard, A. S.; Michael, J. P.
Alkaloids (N.Y.) 1986, 28, 183. (c) Michael, J. P. Natural
Products Reports 1990, 485.
BnO(CH ) MgBr to 9b followed by the reductive deoxgenation with
2 4
Et SiH-BF •OEt provided the pyrrolidine derivative 13 with extremely
3
3
2
high stereoselectivity (98:2 determined by HPLC using Daicel
Chiralpak AS). After separation of the major component, the benzyl
(4) (a) Pastuszak, I.; Molyneux, R. J.; James, L. F.; Elbein, A. D.
Biochemistry 1990, 29, 1886. (b) Molyneux, R. J. J. Nat. Prod.
1990, 53, 609.
27
substituent in 13 ([α]D +6.85° (c 1.78, CHCl )) was replaced by the
3
26
leaving group to give the corresponding tosylate 14 ([α]D +7.71° (c
1.34, CHCl )) in good yield. Finally, 14 was subjected to deprotections
3
(5) Yoda, H.; Kitayama, H.; Katagiri, T.; Takabe, K. Tetrahedron:
Asymmetry 1993, 4, 1455.
12
with BF •OEt
and in turn cyclization under basic conditions to
3
2
27
complete the total synthesis of (+)-lentiginosine (4) ([α]D +3.20° (c
(6) (a) Brandi, A.; Cicchi, S.; Cordero, F. M.; Frignoli, R.; Goti, A.;
Picasso, S.; Vogel, P. J. Org. Chem. 1995, 60, 6806. (b) Cordero,
F. M.; Cicchi, S.; Goti, A.; Brandi, A. Tetrahedron Lett. 1994, 35,
949 and the other syntheses are as follows: (c) Gurjar, M. K.;
Ghosh, L.; Syamala, M.; Jayasree, V. Tetrahedron Lett. 1994, 35,
8871. (d) Nukui, S.; Sodeoka, M.; Sasai, H.; Shibasaki, M. J. Org.
Chem. 1995, 60, 398. (e) Giovannini, R.; Marcantoni, E.; Petrini,
M. J. Org. Chem. 1995, 60, 5706.
25
6a
1.07, CH OH) [lit. [α]D +3.2° (c 0.27, CH OH)] ) in high yield. The
3
3
spectral data of the synthetic 4 were completely identical with those of
4
5,6
the reported natural and synthetic compound.
(7) (a) Gruters, R. A.; Neefjes, J. J.; Tersmette, M.; de Goede, R. E.
Y.; Tulp, A.; Huisman, H. G.; Miedema, F.; Ploegh, H. L. Nature
1987, 330, 74. (b) Fleet, G.W. J.; Karpas, A.; Dwek, R. A.;
Fellows, L. E.; Tyms, A. S.; Petursson, S.; Namgoong, S. K.;
Ramsden, N. G.; Smith, P. W.; Son, J. C.; Wilson, F.; Witty, D.
R.; Jacob, G. S.; Rademacher, T. FEBS Lett. 1988, 237, 128.
(8) Molyneux, R. J.; Pan, Y. T.; Tropea, J. E.; Benson, M.; Kaushal,
G. P.; Elbein, A. D. Biochemistry 1991, 30, 9981.
(9) (a) Yoda, H.; Nakajima, T.; Yamazaki, H.; Takabe, K.
Heterocycles 1995, 41, 2423. (b) Yoda, H.; Yamazaki, H.;
Kawauchi, M.; Takabe, K. Tetrahedron: Asymmetry 1995, 6,
2669. (c) Yoda, H.; Yamazaki, H.; Takabe, K. Tetrahedron:
Asymmetry 1996, 7, 373 and references cited therein.
In summary, an efficient and novel synthetic pathway from D-xylose to
a dihydroxyindolizidine alkaloid, (+)-lentiginosine has been established
employing the stereoselective deoxygenation of α-hydroxypyrrolidine
as a key step, which will furthermore serve for the synthesis other
natural products.
(10) Yoda, H.; Nakajima, T.; Takabe, K. Tetrahedron Lett. 1996, 37,
5531.
(11) The newly created stereogenic centers of 11 and 12 were easily
determined to be S and R respectively as indicated in Scheme 2
13
References and Notes
based on the observed chemical shift of C NMR, since the
authentic 12a was quickly prepared through the successive
reactions of reduction and mesylation followed by cyclization
from 15, which was in turn elaborated according to our reported
(1) (a) Elbein, A. D. (Inhibitors of the Biosynthesis and Processing of
N-linked Oligosaccharide Chains.) Annu. Rev. Biochem. 1987, 56,
497. (b) Fellows, L. E.; Kite, G. C.; Nash, R. J.; Simmonds, M. S.
J.; Scofield, A. M. In Plant Nitrogen Metabolism; Poulton, J. E.,
Romero, J. T., Conn, E. E., Eds.; Plenum: New York, 1989; pp
395. (c) Legler, G. Adv. Carbohydr. Chem. Biochem. 1990, 48,
319.
9b
method.
(2) (a) Humphries, M. J.; Matsumoto, K.; White, S. L.; Olden, K.
Cancer Res. 1986, 46, 5215. (b) Liu, P. S.; Hoekstra, W. J.; King,
C.-H. R. Tetrahedron Lett. 1990, 31, 2829.
(12) Yoda, H.; Oguchi, T.; Takabe, K. Tetrahedron Lett. 1997, 38,
3283.