A Facile One-Pot Synthesis of 7-Triethylsilylbaccatin III

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

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.