Total Synthesis of (+)-Brefeldin
C Utilizing Aza-Claisen Rearrangement

Makoto Inai; Takeshi Nishii; Shingo Mukoujima; Tomoyuki Esumi; Hiroto Kaku; Keiko Tominaga; Hiroaki Abe; Mitsuyo Horikawa; Tetsuto Tsunoda

doi:10.1055/s-0030-1260762

LETTER

Total Synthesis of (+)-Brefeldin C Utilizing Aza-Claisen Rearrangement

Makoto Inai, Takeshi Nishii, Shingo Mukoujima, Tomoyuki Esumi, Hiroto Kaku, Keiko Tominaga, Hiroaki Abe, Mitsuyo Horikawa, Tetsuto Tsunoda*
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8514, Japan
Fax: +81(88)6553051; e-Mail: tsunoda@ph.bunri-u.ac.jp;

Abstract

Alle Artikel dieser Rubrik

Abstract

The total synthesis of (+)-brefeldin C was accomplished. An asymmetric aza-Claisen rearrangement developed by our laboratory was employed to construct the C-4 and C-5 stereogenic centers of (+)-brefeldin C as a key step.

Key words

aza-Claisen rearrangement - amide enolate - asymmetric synthesis - brefeldin C - natural product synthesis

Volltext

Referenzen

References and Notes

<A NAME="RU02411ST-1A">1a</A> Tsunoda T. Sakai M. Sasaki O. Sako Y. Hondo Y. Itô S. Tetrahedron Lett. 1992, 33: 1651

<A NAME="RU02411ST-1B">1b</A> Tsunoda T. Tatsuki S. Shiraishi Y. Akasaka M. Itô S. Tetrahedron Lett. 1993, 34: 3297

<A NAME="RU02411ST-2A">2a</A> Itô S. Tsunoda T. Pure Appl. Chem. 1994, 66: 2071

<A NAME="RU02411ST-2B">2b</A> Tsunoda T. Ozaki F. Shirakata N. Tamaoka Y. Yamamoto H. Itô S. Tetrahedron Lett. 1996, 37: 2463

<A NAME="RU02411ST-2C">2c</A> Tsunoda T. Nishii T. Yoshizuka M. Yamasaki C. Suzuki T. Itô S. Tetrahedron Lett. 2000, 41: 7667

<A NAME="RU02411ST-2D">2d</A> Nishii T. Suzuki S. Yoshida K. Arakaki K. Tsunoda T. Tetrahedron Lett. 2003, 44: 7829

<A NAME="RU02411ST-2E">2e</A> Yu S. Pan X. Lin X. Ma D. Angew. Chem. Int. Ed. 2005, 44: 135

<A NAME="RU02411ST-2F">2f</A> Yu S. Pan X. Ma D. Chem. Eur. J. 2006, 12: 6572

<A NAME="RU02411ST-2G">2g</A> Li W. Schlecker A. Ma D. Chem. Commun. 2010, 46: 5403

<A NAME="RU02411ST-3">3</A> Sunagawa M. Ohta T. Nozoe S. Heterocycles 1979, 13: 267

<A NAME="RU02411ST-4A">4a</A> Haerri E. Loeffler W. Sigg HP. Staehelin H. Tamm C. Helv. Chim. Acta 1963, 46: 1235

<A NAME="RU02411ST-4B">4b</A> Betina V. Drobnica L. Nemec P. Zemanova M. J. Antibiot. 1964, 17: 93

<A NAME="RU02411ST-4C">4c</A> Takatsuki A. Yamaguchi I. Tamura G. Misato T. Arima K. J. Antibiot. 1969, 22: 442

<A NAME="RU02411ST-4D">4d</A> Tamura G. Ando K. Suzuki S. Takatsuki A. Arima K. J. Antibiot. 1968, 21: 161

<A NAME="RU02411ST-4E">4e</A> Misumi Y. Misumi Y. Miki K. Takatsuki A. Tamura G. Ikehara Y. J. Biol. Chem. 1986, 261: 11398

<A NAME="RU02411ST-5">5</A> Zeeh J.-C. Zeghouf M. Grauffel C. Guibert B. Martin E. Dejaegere A. Cherfils J. J. Biol. Chem. 2006, 281: 11805

<A NAME="RU02411ST-6A">6a</A> Schreiber SL. Meyers HV. J. Am. Chem. Soc. 1988, 110: 5198

<A NAME="RU02411ST-6B">6b</A> Hatakeyama S. Osanai K. Numata H. Takano S. Tetrahedron Lett. 1989, 30: 4845

<A NAME="RU02411ST-6C">6c</A> Archambaud S. Aphecetche-Julienne K. Guingant A. Synlett 2005, 139

<A NAME="RU02411ST-6D">6d</A> Archambaud S. Legrand F. Aphecetche-Julienne K. Collet S. Guingant A. Evain M. Eur. J. Org. Chem. 2010, 1364

For a synthesis of a lactam analogue of BFC, see:

<A NAME="RU02411ST-6E">6e</A> Förster S. Helmchen G. Synlett 2008, 831

<A NAME="RU02411ST-7A">7a</A> Blakemore PR. Cole WJ. Kocienski PJ. Morley A. Synlett 1998, 26

<A NAME="RU02411ST-7B">7b</A> Blakemore PR. J. Chem. Soc., Perkin Trans. 1 2002, 2563

<A NAME="RU02411ST-8">8</A> Similar strategy for construction of C4 and C5 stereogenic centers using sigmatropic rearrangement has been reported, see: Tomooka K. Ishikawa K. Nakai T. Synlett 1995, 901

<A NAME="RU02411ST-9">9</A> Salomon RG. Ghosh S. Zagorski MG. Reitz M. J. Org. Chem. 1982, 47: 829

<A NAME="RU02411ST-10A">10a</A> Tsunoda T. Otsuka J. Yamamiya Y. Itô S. Chem. Lett. 1994, 539

<A NAME="RU02411ST-10B">10b</A> Tsunoda T. Yamamiya Y. Kawamura Y. Itô S. Tetrahedron Lett. 1995, 36: 2529

<A NAME="RU02411ST-11">11</A> For a review of Birch reaction. see: Rabideau PW. Marcinow Z. Org. React. 1992, 42: 1

<A NAME="RU02411ST-12A">12a</A> Dess DB. Martin JC. J. Org. Chem. 1983, 48: 4155

<A NAME="RU02411ST-12B">12b</A> Dess DB. Martin JC. J. Am. Chem. Soc. 1991, 113: 7277

<A NAME="RU02411ST-13">13</A> Inanaga J. Hirata K. Saeki H. Katsuki T. Yamaguchi M. Bull. Chem. Soc. Jpn. 1979, 52: 1989

(+)-Brefeldin C
[α]_D ^¹9 +119.8 (c 1.00, CHCl₃) {lit.^6d [α]_D ^²0 +121 (c 0.07, MeOH)}. ^¹H NMR (600 MHz, CDCl₃): δ = 7.38 (dd, J = 15.6, 3.0 Hz, 1 H), 5.91 (dd, J = 15.6, 1.92 Hz, 1 H), 5.73 (ddd, J = 15.1, 10.4, 4.7 Hz, 1 H), 5.19 (dd, J = 15.1, 9.6 Hz, 1 H), 4.86 (dqd, J = 10.8, 6.3, 1.9 Hz, 1 H), 4.10 (br d, J = 9.6 Hz, 1 H), 2.25 (quin, J = 8.8 Hz, 1 H), 2.03-1.98 (m, 2 H), 1.89-1.81 (m, 3 H), 1.76-1.51 (m, 6 H), 1.41-1.35 (m, 1 H), 1.26 (d, J = 6.3 Hz, 3 H), 0.98-0.92 (m, 1 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 166.3, 152.0, 136.3, 130.3, 117.3, 76.0, 71.7, 54.0, 46.9, 35.1, 34.1, 31.9, 31.8, 26.8, 25.2, 20.9. IR (ATR): 3406, 2933, 1713 cm^-¹. MS (CI): m/z = 265 [M + H]⁺, 247 (base peak), 201. HRMS (CI): m/z [M + H]⁺ calcd for C₁₆H₂₅O₃: 265.18036; found: 265.1789.