Method for synthesizing epothilones and epothilone analogs

Details Method for synthesizing epothilones and epothilone analogs Method for synthesizing epothilones and epothilone analogs

2005-10-25

2005-10-25

Saeed, Kamal A. (Department: 1626)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C548S204000

Reexamination Certificate

active

06958401

ABSTRACT:
A method for making epothilones and epothilone analogs is described, as are novel compounds made by the method. One embodiment of the method was used to synthesize epothilone B by a convergent approach that entailed Wittig coupling of an ylide derived from phosphonium bromide with an aldehyde. The former was prepared from propargyl alcohol by a nine-step pathway which installed both trisubstituted double bonds with clean Z configuration. Macrolactonization of a resulting seco acid provided the following intermediate diene epothilone analog. Selective saturation of the 9,10-olefin and subsequent epoxidation provided epothilone B.

REFERENCES:
patent: 4551433 (1985-11-01), DeBoer
patent: 4874748 (1989-10-01), Katz et al.
patent: 5063155 (1991-11-01), Cox et al.
patent: 5098837 (1992-03-01), Beckmann et al.
patent: 5149639 (1992-09-01), Katz et al.
patent: 5969145 (1999-10-01), Schinzer et al.
patent: 6043372 (2000-03-01), Schinzer et al.
patent: 6090601 (2000-07-01), Gustafsson et al.
patent: 6302838 (2001-10-01), O'Reilly et al.
patent: 6303342 (2001-10-01), Julien et al.
patent: 6358719 (2002-03-01), Schupp et al.
patent: 6410301 (2002-06-01), Julien et al.
patent: 6441186 (2002-08-01), Nicolaou et al.
patent: 6723854 (2004-04-01), Danishefsky et al.
patent: 2002/0058817 (2002-05-01), Danishefsky et al.
patent: 2002/0062030 (2002-05-01), White et al.
patent: WO 93/10121 (1993-05-01), None
patent: WO 97/19086 (1997-05-01), None
patent: WO 98/22461 (1998-05-01), None
patent: WO 98/38192 (1998-09-01), None
patent: WO 98/08849 (1998-10-01), None
Nicolaou et al., 2002, CAS:137:185358.
Danishefsky et al., 1999, CAS:130:124934.
Claims as Pending in U.S. Appl. No. 09/846,154, filed Apr. 30, 2001 (Pub. No. 2002/0062030, published May 23, 2002).
Applicants' copending U.S. Appl. No. 10/354,694, filed Jan. 29, 2003.
Applicants' U.S. Appl. No. 09/499,596, filed Feb. 7, 2000, now abandoned.
Protest Filed Under 37 CFR § 1.291, U.S. Appl. No. 09/846,154, 30 pages. Served on applicants on Feb. 10, 2003.
Rivkin et al. Complex Target-Oriented Total Synthesis in the Drug Discovery Process: The Discovery of a Highly Promising Family of Second Generation Epothilones.J. Am. Chem. Soc.2003, published on the Web Feb. 6, 2003.
White et al. Synthesis, Conformational Analysis, and Bioassay of 9,10-Didehydroepothilone D.Org. Lett.2002, 4, 995-997. Published on the Web Feb. 27, 2002.
White et al. Total Synthesis of Epothilone B, Epothilone D, andcis-andtrans-9,10-Dehydroepothilone D.J. Am. Chem. Soc.2001, 123, 5407-5413.
White et al. Total Synthesis of Epothilone B, Epothilone D, andcis-andtrans-9 ,10-Dehydroepothilone D [J. Am. Chem. Soc.2001, 123, 5407-5413]. ACS Publications Division Home Page. http://pubs.acs.org (accessed Feb. 3, 2003).
Höfle, G.; Bedorf, N.; Gerth, H.; Reichenbach, H.Chem. Abstr., 120, 52841, 1993.
Höfle G.; Bedorf, N.; Steinmeth, H.; Schomburg, D.; Gerth. H.; Reichenbach, H.Angew. Chem. Int. Ed. Engl., 35, 1567, 1996.
Gerth, K., et al.,Antibiot., 49, 560-563, 1996.
Kirschner et al.,Cell, 45, 329-342, 1986.
Mitchison et al.,Nature, 312, 237-242, 1984.
Toso R. J.,Biochemistry, 32, 1285-1293, 1993.
Kowalski R. J., et al.,J. Biol. Chem., 272, 2534-2541, 1997.
Nicolaou, K.C.; Ninkovic, S.; Sarabia, F.; Vourloumis, D.; He, Y.; Vallberg, H.; Finlay, M.R.V.; Yang, Z.J. Am. Chem. Soc., 119, 7974, 1997.
Meng, D.; Bertinato , P.; Balog, A.; Su, D.-S.; Kamenecka, T.; Sorensen, E.J.; Danishefsky, S.J.J. Am. Chem. Soc., 119, 10073, 1997.
May, S.A.; Grieco, P.Chem. Commun., 1597, 1998.
Schinzer, D.; Bauer, A.; Schieber, J.Synlett, 861, 1998.
White, J.D.; Tiller, T.; Ohba, Y.; Porter, W.J., Jackson, R.W.; Wang, S.; Hanselmann, R.;Chem. Commun., 79, 1998.
Mulzer, J.; Mantoulidis, A.Tetrahedron Lett., 37, 9179, 1996.
Claus, E.; Pahl, A.; Jones, P.G.; Meyer, H.M.; Kalesse, M.Tetrahedron Lett., 38, 1359, 1997.
Gabriel, T.; Wessjohann, L.Tetrahedron Lett., 38, 1363, 1997.
Taylor, R.E.; Haley, J.D.Tetrahedron Lett., 38, 2061, 1997.
De Brabander, J.D.; Rosset, S.; Bernardinelli, G.Synlett, 824, 1997.
Chakraborty, J.K.; Dutta, S.Tetrahedron Lett., 39, 101, 1998.
Liu, Z.-Y.; Yu, C.-Z.; Yang, J.D.Synlett, 1383, 1997.
Liu, Z.-Y.; Yu, C.-Z; Wang, R.-F.; Li, G.Tetrahedron Lett., 39, 5261, 1998.
Mulzer, J.; Mantoulidis, A.; Öhler, E.Tetrahedron Lett., 38, 7725, 1997.
Bijoy, P.; Avery, M.A.Tetrahedron Lett. 39, 209, 1998.
Su et al.,Angew. Chem. Int. Ed. Engl., 36, 757, 1997.
Gilbert et al.,J. Org. Chem., 47, 1837, 1982.
Inanaga et al.,Bull Chem. Soc. Jpn., 1979, 52, 1989.
Müller et al.,Synlett, p. 521, 1996.
Farina and Krishnan,J. Am. Chem. Soc., 113, 9585, 1991.
Balog et al.,Angew. Chem. Int Ed. Engl, 35, 2801, 1996.
Nicolaou et al.,Angew. Chem. Int Ed. Engl, 35, 2399, 1996.
Nicolaou et al.,Angew. Chem. Int Ed. Engl., 36, 2097, 1997.
Nicolaou et al.,Angew. Chem. Int Ed. Engl., 37, 2015, 1998.

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