Synlett 2019; 30(05): 577-580
DOI: 10.1055/s-0037-1611727
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of the C1–C17 Segment of Bafilomycin N

Haruka Sato
,
Seijiro Hosokawa*
Department of Applied Chemistry, Faculty of Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555, Japan   Email: seijiro@waseda.jp
› Author Affiliations
We are grateful for the financial support from the Sumitomo Foundation and the Tokyo Biochemical Research Foundation. This work was also supported by Grant-in-Aid for Scientific Research on Innovative Areas ‘Frontier Research on Chemical Communications’ (Grant no. 18H04632).
Further Information

Publication History

Received: 21 December 2018

Accepted after revision: 21 January 2019

Publication Date:
21 February 2019 (online)


Abstract

The C1–C17 segment of bafilomycin N has been synthesized. The C1–C11 segment was synthesized by the anti-selective vinylogous Mukaiyama aldol reaction with a chiral vinylketene silyl N,O-acetal and the Horner–Wadsworth–Emmons reaction, whereas C12–C17 was constructed by the syn-selective vinylogous Mukaiyama aldol reaction and the Jung’s semipinacol rearrangement. Those segments were connected by the Stille coupling to afford the C1–C17 segment.

Supporting Information

 
  • References and Notes

  • 1 Chen Y.-H, Yang J.-C, Lu M.-C, Weng CF, Su YDi. Kuo J., Wu Y. C., Sung P. J. 2017; 73: 5170
    • 2a Werner G, Hagenmaier H, Albert K, Kohlshorn H. Tetrahedron Lett. 1983; 24: 5193
    • 2b Corey EJ, Ponder JW. Tetrahedron Lett. 1984; 25: 4325
    • 2c Baker GH, Brown PJ, Dorgan RJ. J, Everett JR, Ley SV, Slawin AM. Z, Williams DJ. Tetrahedron Lett. 1987; 28: 5565
    • 3a Werner G, Hagenmaier H, Drautz H, Baumgartner A, Zähner H. J. Antibiot. 1984; 37: 110
    • 3b Yoshimori T, Yamamoto A, Moriyama Y, Futai M, Tashiro Y. J. Biol. Chem. 1991; 266: 17707
  • 4 Evans DA, Calter MA. Tetrahedron Lett. 1993; 34: 6871
    • 5a Toshima K, Jyojima T, Yamaguchi H, Murase H, Yoshida T, Matsumura S, Nakata M. Tetrahedron Lett. 1996; 37: 1069
    • 5b Toshima K, Yamaguchi H, Jyojima T, Noguchi Y, Nakata M, Matsumura S. Tetrahedron Lett. 1996; 37: 1073
    • 5c Toshima K, Jyojima T, Yamaguchi H, Noguchi Y, Yoshida T, Murase H, Nakata M, Matsumura S. J. Org. Chem. 1997; 62: 3271
    • 6a Roush WR, Bannister TD. Tetrahedron Lett. 1992; 33: 3587
    • 6b Scheldt KA, Tasaka A, Bannister TD, Wendt MD, Roush WR. Angew. Chem. Int. Ed. 1999; 38: 1652
    • 6c Scheidt KA, Bannister TD, Tasaka A, Wendt MD, Savall BM, Fegley GJ, Roush WR. J. Am. Chem. Soc. 2002; 124: 6981
    • 6d Roush WR, Bannister TD, Wendt MD, Jablonowski JA, Scheidt KA. J. Org. Chem. 2002; 67: 4275
    • 7a Hanessian S, Ma J, Wang W. J. Am. Chem. Soc. 2001; 123: 10200
    • 7b Hanessian S, Ma J, Wang W, Gai Y. J. Am. Chem. Soc. 2002; 124: 7249
    • 8a Kleinbeck F, Carreira EM. Angew. Chem. Int. Ed. 2009; 48: 578
    • 8b Kleinbeck F, Fettes GJ, Fader LD, Carreira EM. Chem. Eur. J. 2012; 18: 3598
    • 9a Shirokawa S, Kamiyama M, Nakamura T, Okada M, Nakazaki A, Hosokawa S, Kobayashi S. J. Am. Chem. Soc. 2004; 126: 13604
    • 9b Mukaeda Y, Kato T, Hosokawa S. Org. Lett. 2012; 14: 5298
    • 9c Tsukada H, Mukaeda Y, Hosokawa S. Org. Lett. 2013; 15: 678
    • 9d Sagawa N, Sato H, Hosokawa S. Org. Lett. 2017; 19: 198
    • 9e Sagawa N, Moriya H, Hosokawa S. Org. Lett. 2017; 19: 250
  • 10 Takahashi Y, Otsuka M, Harachi M, Mukaeda Y, Hosokawa S. Org. Lett. 2014; 16: 4106
  • 11 Nakamura T, Kubota K, Ieki T, Hosokawa S. Org. Lett. 2016; 18: 132
  • 12 Sekiya S, Okumura M, Kubota K, Nakamura T, Sekine D, Hosokawa S. Org. Lett. 2017; 19: 2394
    • 13a Hosokawa S. J. Synth. Org. Chem., Jpn 2017; 75: 831
    • 13b Hosokawa S. Acc. Chem. Res. 2018; 51: 1301
    • 14a Nakamura T, Harachi M, Kano T, Mukaeda Y, Hosokawa S. Org. Lett. 2013; 15: 3170
    • 14b Kato T, Sato T, Kashiwagi Y, Hosokawa S. Org. Lett. 2015; 17: 2274
    • 14c Nakamura T, Nakagome H, Sano S, Sadayuki T, Hosokawa S. Chem. Lett. 2016; 45: 550
    • 14d Ejima H, Wakita F, Imamura R, Kato T, Hosokawa S. Org. Lett. 2017; 19: 2530
  • 15 Yamaoka H, Nakazaki A, Kabayashi S. Tetrahedron Lett. 2010; 51: 287
  • 16 Zhu G, Negishi E. Chem. Eur. J. 2008; 14: 311
  • 17 For NOESY and COSY spectra of compound 6, see Supporting Information.
    • 18a Marshall JA, Adams ND. J. Org. Chem. 2002; 67: 733
    • 18b Quéron E, Lett R. Tetrahedron Lett. 2004; 45: 4527
  • 19 Shinoyama M, Shirokawa SI, Nakazaki A, Kobayashi S. Org. Lett. 2009; 11: 1277
  • 20 CCDC 1892179 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif or by emailing data_request@ccdc.cam.ac.uk or by contacting The Cambridge Crystallographic Data Centre 12 Union Road Cambridge CB2 1EZ, U.K.
  • 21 Wang Z, Campagna S, Yang K, Xu G, Pierce ME, Fortunak JM, Confalone PN. J. Org. Chem. 2000; 65: 1889
    • 22a Jung ME, D’Amico DC. J. Am. Chem. Soc. 1993; 115: 12208
    • 22b Jung ME, D’Amico DC. J. Am. Chem. Soc. 1997; 119: 12150
  • 23 For the NOESY spectrum of compound 26, see Supporting Information.
  • 24 Synthesis of C1–C17 Segment 4 To a solution of C1–C11 segment 6 (9.6 mg, 0.0184 mmol) and C12–C17 segment 7 (7.7 mg, 0.0184 mmol) in NMP (0.2 mL) was added LiCl (2.4 mg, 0.0553 mmol, 3.0 equiv) and Pd2(dba)3 ·CHCl3 at rt. After stirring for 4 h, the reaction was diluted with Et2O (0.2 mL) and H2O (0.2 mL). The resulting two-phase mixture was filtered through a pad of celite. After the layers had been separated, the aqueous layer was extracted with Et2O (5 × 0.1 mL). The combined organic layers were dried with Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/EtOAc = 15:1) to give the C1–C17 segment 4 as a yellowish oil (9.4 mg, 0.0154 mmol, 84%). Rf = 0.21 (n-hexane/ethyl acetate = 5:1). [α]D 20 +46.6 (c 0.28, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.11 (s, 1 H), 6.22 (ddd, J = 15.0, 11.0, 1.0 Hz, 1 H), 5.80 (d, J = 10.0 Hz, 1 H), 5.76 (d, J = 11.0 Hz, 1 H), 5.50 (dd, J = 15.0, 9.0 Hz, 1 H), 3.60 (dd, J = 6.5, 3.0 Hz, 1 H), 3.58 (ddd, J = 11.0, 7.0, 5.5 Hz, 1 H), 3.49 (ddd, J = 11.0, 5.5, 5.5 Hz, 1 H), 3.41 (dd, J = 5.0, 3.0 Hz, 1 H), 2.73–2.65 (m, 1 H), 2.40–2.33 (m, 1 H), 2.31–2.25 (m, 1 H), 2.01 (d, J = 1.0 Hz, 3 H), 1.91–1.85 (m, 1 H), 1.84 (d, J = 1.0 Hz, 3 H), 1.80–1.68 (m, 2 H), 1.67 (s, 3 H), 1.00 (d, J = 6.0 Hz, 3 H), 0.98 (d, J = 6.5 Hz, 3 H), 0.91 (s, 9 H), 0.87 (d, J = 7.0 Hz, 3 H), 0.74 (d, J = 6.5 Hz, 3 H), 0.08 (s, TMS, 9 H), 0.05 (s, TBS, 3 H), 0.04 (s, TBS, 3 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 169.8, 143.6, 139.4, 135.5, 135.4, 130.1, 126.7, 126.6, 134.8, 80.2, 77.5, 66.1, 51.8, 43.9, 41.2, 38.8, 36.6, 35.8, 26.12, 26.10, 19.3, 18.4, 18.2, 16.6, 16.3, 15.6, 14.1, 11.0, 0.8, 0.7, –3.77, –3.80 ppm. HRMS (ESI): m/z [M + Na]+ calcd for C34H64O5NaSi2: 631.4184; found: 631.4179. IR (KBr film): 3469, 2958, 2929, 2857, 1712, 1250, 1117, 1033, 837, 773, 750 cm–1.