Multifunctionality of the N-Trichloroacetyl Group Developed in the Synthesis of Tetrodotoxin, a Puffer Fish Toxin

Toshio Nishikawa; Daisuke Urabe; Masaatsu Adachi; Minoru Isobe

doi:10.1055/s-0034-1380781

Synlett, Inhaltsverzeichnis

Synlett 2015; 26(14): 1930-1939
DOI: 10.1055/s-0034-1380781

account

Multifunctionality of the N-Trichloroacetyl Group Developed in the Synthesis of Tetrodotoxin, a Puffer Fish Toxin

Toshio Nishikawa*

^aGraduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan eMail: nisikawa@agr.nagoya-u.ac.jp

,

Daisuke Urabe

^bGraduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

,

Masaatsu Adachi

^aGraduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan eMail: nisikawa@agr.nagoya-u.ac.jp

,

Minoru Isobe*

^cDepartment of Chemistry, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan eMail: minoru@mail.nsysu.edu.tw

› Institutsangaben

Abstract

Alle Artikel dieser Rubrik

Abstract

This account describes a serendipitous discovery and the development of unique reactions associated with trichloroacetamide during synthetic studies of tetrodotoxin in our laboratory. The reactions include site-selective hydroxylation using the neighboring-group participation of trichloroacetamide, guanidinylation from a trichloroacetamide, protecting-group transformation, and removal of the N-trichloroacetyl group. These studies indicate the importance of the total synthesis of densely functionalized natural products as a field for the development of new reactions.

1 Introduction

2 Improvement of the Conditions for the Overman Rearrangement to Introduce Trichloroacetamide

3 Site-Selective Hydroxylation Using the Neighboring-Group Participation of Trichloroacetamide

4 Guanidine Synthesis

5 Protecting-Group Transformation of the N-Trichloroacetyl Group

6 New Deprotection Conditions for the Removal of the N-Trichloroacetyl Group

7 Conclusion

Key words

protecting groups - tetrodotoxin - trichloroacetamide - neighboring-group effects - protecting-group transformations

Volltext

Referenzen

References

Reviews:

1a Kocienski PJ. Protecting Groups . 3rd ed. Georg Thieme Verlag; Stuttgart: 2005
1b Wuts PG. M, Greene TW. Greene’s Protective Groups in Organic Synthesis. 5th ed. John Wiley & Sons; Hoboken NJ: 2014

2 Schelhaas M, Waldmann H. Angew. Chem. Int. Ed. Engl. 1996; 35: 2056

Reviews:

3a Hoffman RW. Synthesis 2006; 3531
3b Young IS, Baran PS. Nat. Chem. 2009; 1: 193
3c Saicic RN. Tetrahedron 2014; 70: 8183

4 Nishikawa T, Isobe M. Chem. Rec. 2013; 13: 286

Recent reviews of the chemistry and biology of tetrodotoxin:

5a Moczydlowski EG. Toxicon 2013; 63: 165
5b Narahashi T. Proc. Jpn. Acad., Ser. B 2008; 84: 147

Syntheses of the common intermediates:

6a Nishikawa T, Asai M, Ohyabu N, Yamamoto N, Fukuda Y, Isobe M. Tetrahedron 2001; 57: 3875
6b Satake Y, Nishikawa T, Hiramatsu T, Araki H, Isobe M. Synthesis 2010; 1992

7a Overman LE. J. Am. Chem. Soc. 1974; 96: 597

For a review, see:

7b Overman LE, Carpenter NE In Organic Reactions . Vol. 66. Overman LE. John Wiley & Sons; New York: 2005: 1-107

8 Nishikawa T, Asai M, Ohyabu N, Isobe M. J. Org. Chem. 1998; 63: 188

9a Takeda K, Kaji E, Konda Y, Sato N, Nakamura H, Miya N, Morizane A, Yanagisawa Y, Akiyama A, Zen S, Harigaya Y. Tetrahedron Lett. 1992; 33: 7145
9b Eguchi T, Kakinuma K. J. Synth. Org. Chem., Jpn. 1997; 55: 814

10a Tsujimoto T, Nishikawa T, Urabe D, Isobe M. Synlett 2005; 433
10b Matsumoto N, Tsujimoto T, Nakazaki A, Isobe M, Nishikawa T. RSC Adv. 2012; 2: 9448

For examples, see:

11a Donohoe TJ, Blades K, Helliwell M, Moore PR, Winter JJ. G, Stemp G. J. Org. Chem. 1999; 64: 2980
11b Takahashi K, Yamaguchi D, Ishihara J, Hatakeyama S. Org. Lett. 2012; 14: 1644
11c Xu C, Wang L, Hao X, Wang DZ. J. Org. Chem. 2012; 77: 6307

12a Nishikawa T, Asai M, Ohyabu N, Yamamoto N, Isobe M. Angew. Chem. Int. Ed. 1999; 38: 3081
12b Asai M, Nishikawa T, Ohyabu N, Yamamoto N, Isobe M. Tetrahedron 2001; 57: 4543

13 Because the thin-layer chromatography (TLC) behavior (R_f values and colors) of 24 and 28 was nearly identical, we did not notice this unusual reaction until NMR spectroscopic measurements of the crude product were obtained. It was later revealed that the repeated development of a TLC plate with dichloromethane as the sole solvent showed slightly different R_f values. If our student had not worked up the crude product and measured the NMR spectra we would not have found this unusual reaction!

14a Nishikawa T, Urabe D, Yoshida K, Iwabuchi T, Asai M, Isobe M. Org. Lett. 2002; 4: 2679
14b Nishikawa T, Urabe D, Yoshida K, Iwabuchi T, Asai M, Isobe M. Chem. Eur. J. 2004; 10: 452

15 Nishikawa T, Koide Y, Adachi M, Isobe M. Bull. Chem. Soc. Jpn. 2010; 83: 66
16 Atanassova IA, Petrov JS, Mollov NM. Synthesis 1987; 734
17 Weygand F, Frauendorfer E. Chem. Ber. 1970; 103: 2437

Guanidine synthesis:

18a Nishikawa T, Ohyabu N, Yamamoto N, Isobe M. Tetrahedron 1999; 55: 4325
18b Yamamoto N, Isobe M. Chem. Lett. 1994; 23: 2299

19 Acetylation of the dibenzylguanidine was required for the next deprotection involving the removal of the benzyl groups by hydrogenolysis with palladium(II) hydroxide on carbon.
20 Nishikawa T, Urabe D, Tomita M, Tsujimoto T, Iwabuchi T, Isobe M. Org. Lett. 2006; 8: 3263
21 Adachi M, Imazu T, Sakakibara R, Satake Y, Isobe M, Nishikawa T. Chem. Eur. J. 2014; 20: 1247
22 Oishi T, Ando K, Inomiya K, Sato H, Iida M, Chida N. Org. Lett. 2002; 4: 151
23 Urabe D, Nishikawa T, Isobe M. Chem. Asian J. 2006; 1: 125
24 In general we used Na₂CO₃ to generate the isocyanate. Potassium carbonate was used in this case because of a misunderstanding by our student, who soon observed the removal of the N-trichloroacetyl group.
25 Urabe D, Sugino K, Nishikawa T, Isobe M. Tetrahedron Lett. 2004; 45: 9405
26 Adachi M, Imazu T, Isobe M, Nishikawa T. J. Org. Chem. 2013; 78: 1699
27 Satake Y, Adachi M, Tokoro S, Yotsu-Yamashita M, Isobe M, Nishikawa T. Chem. Asian J. 2014; 9: 1922
28 Adachi M, Sakakibara R, Satake Y, Isobe M, Nishikawa T. Chem. Lett. 2014; 43: 1719
29 This deprotection condition was used in other laboratories; for examples, see: Nie L.-D, Wang F.-F, Ding W, Shi X.-X, Lu X. Tetrahedron: Asymmetry 2013; 24: 638

For other uses of trichloroacetamide, see:

30a Nagashima H, Wakamatsu H, Itoh K. J. Chem. Soc., Chem. Commun. 1984; 652
30b Seigal BA, Fajardo C, Snapper ML. J. Am. Chem. Soc. 2005; 127: 16329
30c Diaba F, Martínez-Laporta A, Bonjoch J, Pereira A, Muñoz-Molina JM, Pérez PJ, Belderrain TR. Chem. Commun. 2012; 48: 8799
30d Li Q, Li G, Ma S, Feng P, Shi Y. Org. Lett. 2013; 15: 2601

31 Trichloroacetimidate, which is related to the N-trichloroacetyl group, is also useful for several transformations owing to neighboring-group participation, although it is not a protecting group; for examples, see: Kang SH, Kang SY, Lee H.-S, Buglass AJ. Chem. Rev. 2005; 105: 4537
32 Ueda M. Chem. Lett. 2012; 41: 658