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Total Synthesis of the Natural Enantiomer of (−)-Lepadiformine and Determination of Its Absolute Stereochemistry^†

Hideki Abe

School of Pharmacy, Tokyo University of Pharmacy & Life Science 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392 (Japan) Fax: (+81) 426-76-4475

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Sakae Aoyagi,

Sakae Aoyagi

School of Pharmacy, Tokyo University of Pharmacy & Life Science 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392 (Japan) Fax: (+81) 426-76-4475

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Chihiro Kibayashi Prof. Dr.,

Chihiro Kibayashi Prof. Dr.

[email protected]

School of Pharmacy, Tokyo University of Pharmacy & Life Science 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392 (Japan) Fax: (+81) 426-76-4475

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Hideki Abe,

Hideki Abe

School of Pharmacy, Tokyo University of Pharmacy & Life Science 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392 (Japan) Fax: (+81) 426-76-4475

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Sakae Aoyagi,

Sakae Aoyagi

School of Pharmacy, Tokyo University of Pharmacy & Life Science 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392 (Japan) Fax: (+81) 426-76-4475

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Chihiro Kibayashi Prof. Dr.,

Chihiro Kibayashi Prof. Dr.

[email protected]

School of Pharmacy, Tokyo University of Pharmacy & Life Science 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392 (Japan) Fax: (+81) 426-76-4475

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First published: 21 August 2002

https://doi.org/10.1002/1521-3773(20020816)41:16<3017::AID-ANIE3017>3.0.CO;2-1

Citations: 56

^†

This work was supported in part by a Grant for Private Universities provided by the Ministry of Education, Sports, and Culture of Japan and the Promotion and Mutual Aid Corporation for Private Schools of Japan. We are grateful to Professor J. F. Biard for a sample of natural lepadiformine.

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Graphical Abstract

A short synthesis: The naturally occurring (−)-lepadiformine ((−)-3) was prepared in nine steps in 31.4 % overall yield. The key step involved the formation of 2 by the spirocyclization of the N-acyliminium ion generated from 1. Furthermore, HPLC analysis of the synthetic material and the natural product established the absolute configuration of 3 as 3S,5R,7aS,11aS. Bn=benzyl, Boc=tert-butoxycarbonyl.

References

1J. F. Biard, S. Guyot, C. Roussakis, J. F. Verbist, J. Vercauteren, J. F. Weber, K. Boukef, Tetrahedron Lett. 1994, 35, 2691–2694.
10.1016/S0040-4039(00)77007-9
CAS Web of Science® Google Scholar
2M. Jugé, N. Grimaud, J. F. Biard, M. P. Sauviat, M. Nabil, J. F. Verbist, J. Y. Petit, Toxicon 2001, 39, 1231–1237.
10.1016/S0041-0101(01)00079-4
CAS PubMed Web of Science® Google Scholar
3
3aK. M. Werner, J. M. de los Santos, S. M. Weinreb, J. Org. Chem. 1999, 64, 686–687;
10.1021/jo981897+
CAS PubMed Web of Science® Google Scholar
3bK. M. Werner, J. M. de los Santos, S. M. Weinreb, J. Org. Chem. 1999, 64, 4865–4873.
10.1021/jo990266s
CAS PubMed Web of Science® Google Scholar
4
4aW. H. Pearson, N. S. Barta, J. W. Kampf, Tetrahedron Lett. 1997, 38, 3369–3372;
10.1016/S0040-4039(97)00632-1
CAS Web of Science® Google Scholar
4bW. H. Pearson, Y. Ren, J. Org. Chem. 1999, 64, 688–689.
10.1021/jo982120j
CAS PubMed Web of Science® Google Scholar
5
5aH. Abe, S. Aoyagi, C. Kibayashi, Tetrahedron Lett. 2000, 41, 1205–1208;
10.1016/S0040-4039(99)02172-3
CAS Web of Science® Google Scholar
5bH. Abe, S. Aoyagi, C. Kibayashi, J. Am. Chem. Soc. 2000, 122, 4583–4592.
10.1021/ja9939284
CAS Web of Science® Google Scholar
6P. Sun, C. Sun, S. M. Weinreb, Org. Lett. 2001, 3, 3507–3510.
10.1021/ol010179y
CAS PubMed Web of Science® Google Scholar
7T. J. Greshock, R. L. Funk, Org. Lett. 2001, 3, 3511–3514.
10.1021/ol0165903
CAS PubMed Web of Science® Google Scholar
8Many attempts at obtaining a crystalline derivative of natural lepadiformine (provided by Professor Biard as an oil) suitable for X-ray crystallography were unsuccessful (W. Pearson, personal communication).
Google Scholar
9For reviews of the chemistry of N-acyliminium ions, see:
Google Scholar
9aW. N. Speckamp, H. Hiemstra, Tetrahedron 1985, 41, 4367–4416;
10.1016/S0040-4020(01)82334-6
CAS Web of Science® Google Scholar
9bH. Hiemstra, W. N. Speckamp in The Alkaloids, Vol. 32 (Ed.: ), Academic Press, San Diego, 1988, pp. 271–339;
10.1016/S0099-9598(08)60218-7
Google Scholar
9cH. Hiemstra, W. N. Speckamp in Comprehensive Organic Synthesis, Vol. 2 (Ed ), Pergamon, Oxford, 1991, pp. 1047–1109;
10.1016/B978-0-08-052349-1.00056-1
Google Scholar
9dW. N. Speckamp, M. J. Moolenaar, Tetrahedron 2000, 56, 3817–3856.
10.1016/S0040-4020(00)00159-9
CAS Web of Science® Google Scholar
10
10aH. E. Schoemaker, W. N. Speckamp, Tetrahedron Lett. 1978, 1515–1518;
10.1016/S0040-4039(01)94590-3
CAS Web of Science® Google Scholar
10bH. E. Schoemaker, W. N. Speckamp, Tetrahedron Lett. 1978, 4841–4844;
10.1016/S0040-4039(01)85748-8
CAS Web of Science® Google Scholar
10cH. E. Schoemaker, W. N. Speckamp, Tetrahedron 1980, 36, 951–958.
Web of Science® Google Scholar
11D. A. Evans, E. W. Thomas, Tetrahedron Lett. 1979, 411–414.
10.1016/S0040-4039(01)93519-1
CAS Web of Science® Google Scholar
12
12aT. Katoh, Y. Nagata, Y. Kobayashi, K. Arai, J. Minami, S. Terashima, Tetrahedron Lett. 1993, 34, 5743–5746;
10.1016/S0040-4039(00)73849-4
CAS Web of Science® Google Scholar
12bT. Katoh, Y. Nagata, Y. Kobayashi, K. Arai, J. Minami, S. Terashima, Tetrahedron 1994, 50, 6221–6238.
10.1016/S0040-4020(01)80643-8
CAS Web of Science® Google Scholar
13For the organometallic ring-opening reaction of N-alkoxycarbonyl lactams, see: A. Giovannini, D. Savoia, A. Umani-Ronchi, J. Org. Chem. 1989, 54, 228–234.
10.1021/jo00262a048
CAS Web of Science® Google Scholar
14J. E. Baldwin, J. Chem. Soc. Chem. Commun. 1976, 734–736.
10.1039/c39760000734
CAS Web of Science® Google Scholar
15The diastereomeric mixture of the formate ester 7 gave a combined signal on a HPLC column. However, the alcohols 11 a and 11 b gave well-separated signals on the HPLC column, and thus the ratio was determined by HPLC integration.
Google Scholar
16R. Noyori, I. Tomino, Y. Tanimoto, J. Am. Chem. Soc. 1979, 101, 3129–3131.
10.1021/ja00505a056
CAS Web of Science® Google Scholar
17For inhibition of hydrogenolysis of benzyl ether groups with PdC in the presence of ammonia and amines, see: H. Sajiki, Tetrahedron Lett. 1995, 36, 3465–3468.
10.1016/0040-4039(95)00527-J
CAS Web of Science® Google Scholar

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Volume41, Issue16

August 16, 2002

Pages 3017-3020

Total Synthesis of the Natural Enantiomer of (−)-Lepadiformine and Determination of Its Absolute Stereochemistry^†

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Total Synthesis of the Natural Enantiomer of (−)-Lepadiformine and Determination of Its Absolute Stereochemistry†

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Total Synthesis of the Natural Enantiomer of (−)-Lepadiformine and Determination of Its Absolute Stereochemistry^†