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

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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

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References

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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.