A Facile One-Pot Synthesis of 7-Triethylsilylbaccatin III

Erkan Baloglu; Michael L. Miller; Emily E. Cavanagh; Tracy P. Marien; Elizabeth E. Roller; Ravi V. J. Chari

doi:10.1055/s-2005-863733

LETTER

A Facile One-Pot Synthesis of 7-Triethylsilylbaccatin III

Erkan Baloglu*, Michael L. Miller, Emily E. Cavanagh, Tracy P. Marien, Elizabeth E. Roller, Ravi V. J. Chari
ImmunoGen Inc., 128 Sidney Street, Cambridge, MA 02139, USA
Fax: +1(617)9952510; e-Mail: erkan.baloglu@immunogen.com;

Abstract

All articles of this category

Abstrac

A one-pot synthesis of 7-triethylsilylbaccatin III has been delineated. The reaction can easily be extended for the preparation of analogs of baccatin III.

Key words

taxol - taxotere - baccatin - paclitaxel - docetaxel

Full Text

References

1a Voegelein-Gueritte F. Guenard D. Lavalle F. LeGoff M.-T. Mangatal L. Potier P. J. Med. Chem. 1991, 992

1b Baloglu E. Kingston DGI. J. Nat. Prod. 1999, 1448

2 Wani MC. Taylor HL. Wall ME. Coggon P. McPhail AT. J. Am. Chem. Soc. 1971, 2325

3 Kingston DGI. Jagtap PG. Yuan H. Samala L. In Progress in the Chemistry of Organic Natural Products Vol. 84: Herz W. Falk H. Kirby GW. Springer-Verlag; Wien / New York: 2002. and the references cited therein

4a Denis JN. Greene AE. Guenard D. Voegelein FG. Mangatal L. Potier P. J. Am. Chem. Soc. 1988, 5917

4b Holton RA, and Somoza C. inventors; US Patent 5654447.

5 Bastart JP, and Pilard J. inventors; PCT Int. Appl. WO 95/26967.

6 Bouchard H, Bourzat JD, Commercon A, and Ojima I. inventors; US Pat. Appl. US2002/0087013 A1.

7 Sisti NJ, Zygmunt J, Brinkman HR, Chander MC, Liang X, and McChesney JD. inventors; US Patent 5914411.

8 Holton RA. Zhang Z. Clarke PAHN. Procter DJ. Tetrahedron Lett. 1998, 39: 288

9

Experimental Procedure for 7-Triethylsilylbaccatin III (4).
To a stirred solution of 10-deacetylbaccatin III (3, 2.72 g, 5 mmol) in pyridine (13.5 mL) was added imidazole (2.04 g, 30 mmol) and chlorotriethylsilane (1.6 mL, 10 mmol) at r.t. The reaction mixture was stirred for 5 min where acetic anhydride (9.5 mL, 100 mmol) was introduced dropwise. The reaction mixture was stirred for additional 4-5 h and when the completion of the reaction is confirmed by MS the reaction was diluted with EtOAc, washed with aq sat. NaHCO₃, H₂O and brine. The organic phase was dried over Na₂SO₄ and the concentrated crude product was purified by column chromatography (EtOAc-hexane, 60:40) to give the desired product (82% yield for two steps).
Analytical data: ¹H NMR (CDCl₃): δ = 8.08 (d, 2 H), 7.58 (t, 1 H), 7.45 (t, 2 H), 6.44 (s, 1 H), 5.61 (d, 1 H), 4.94 (d, 1 H), 4.80 (m, 1 H), 4.48 (m, 1 H), 4.28 (d, 1 H), 4.11 (d, 1 H), 3.86 (d, 1 H), 2.49 (m, 1 H), 2.23 (s, 3 H), 2.22 (t, 3 H), 2.10 (s, 6 H), 1.82 (m, 1 H), 1.68 (d, 1 H), 1.66 (s, 3 H), 1.17 (s, 3 H), 1.01 (s, 3 H), 0.89 (t, 9 H), 0.49-0.63 (m, 6 H). ¹³C NMR (CDCl₃): δ = 202.57, 171.01, 169.67, 167.39, 144.38, 133.91, 132.96, 130.40, 129.74, 128.90, 84.54, 81.15, 79.03, 76.83, 76.13, 75.08, 72.67, 68.21, 58.97, 47.58, 43.09, 38.66, 37.56, 27.11, 22.96, 21.24, 20.42, 15.24, 10.26, 7.05, 5.60. LRMS [MNa]⁺: m/z calcd for C₃₇H₅₂O₁₁SiNa: 723.32; found: 723.20.