Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1996-11-01
1998-11-24
Dentz, Bernard
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
546 48, 423 22, C07D491147
Patent
active
058408983
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to novel chemical compounds that are useful as intermediates in the preparation of camptothecin and camptothecin-like compounds and to processes for their preparation.
BACKGROUND OF THE INVENTION
Useful camptothecin and camptothecin-like compounds that can be produced using intermediates and processes of the present Invention include compounds described in U.S. Pat. No. 4,894,456 to Wall et al. issued Jan. 16, 1990; U.S. Pat. No. 4,399,282 to Miyasaka, et al. issued Aug. 16, 1983; U.S. Pat. No. 4,399,276 to Miyasaka, et al. issued Aug. 16, 1983; U.S. Pat. No. 4,943,579 to Vishnuvajjala, et al. issued Jul. 24, 1990; European Patent Application 0 321 122 A2 filed by SmithKline Beckman Corporation, and published Jun. 21, 1989; U.S. Pat. No. 4,473,692 to Miyasaka, et al. issued Sep. 25, 1984; European Patent application No. 0 325 247 A2 filed by Kabushiki Kaisha Yakult Honsh, and published Jul. 26, 1989; European Patent application 0 556 585 A2 filed by Takeda Chemical Industries, and published Aug. 25, 1993; U.S. Pat. No. 4,981,968 toWall, et al. issued Jan. 1, 1991; U.S. Pat. No. 5,049,668 to Wall, et al. issued Sep. 17, 1991; U.S. Pat. No. 5,180,722 to Wall, et al. issued Jan. 19, 1993 and European Patent application 0 540 099 A1, filed by Glaxo Inc., and published May 5, 1993.
Previous methods used in the preparation of camptothecin and camptothecin-like compounds employ resolutions or chiral auxiliaries to obtain enantiomerically enriched intermediates. A problem with these methods is that a resolution necessitates discarding half of the racemic material and a chiral auxiliary requires utilizing stoichiometric amounts of a chiral subunit to enantioselectively install the chiral center.
The present Invention describes a method for producing enantiomerically enriched intermediates useful for the preparation of camptothecin and camptothecin-like compounds using a process of catalytic asymmetric induction. In this process, a chiral catalyst used in sub-stoichiometric amounts influences the stereoselective formation of the chiral center. Additionally, the process continually regenerates the chiral catalyst preventing waste.
SUMMARY OF THE INVENTION
One aspect of the present invention is a process of providing novel compounds of Formula (I), which are useful as intermediates in the preparation of camptothecin and camptothecin-like compounds, ##STR1## wherein: R.sup.1 represents alkyl, particularly methyl, R.sup.2 represents H or alkyl, particularly methyl, R.sup.3 represents H or alkyl, particularly H; Q represents triflate or halo particularly bromo and iodo more particularly iodo and Y represents chloro or OR.sup.4, wherein R.sup.4 represents alkyl or triflate, or particularly H.
In addition to a process for manufacturing the compounds of Formula (I), other aspects of the invention include the compounds of Formula (I) and various intermediates useful in producing the compounds of Formula (I). Other aspects and advantages of the present invention will become apparent from a review of the detailed description below.
DETAILED DESCRIPTION OF THE INVENTION
The term "alkyl" as used herein means, a linear or branched alkyl group with from 1 to about 8 carbon atoms, such as, but not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, hexyl and octyl. The terms "halo" and "halogen" as used herein refers to a substitutent which may be fluoro, chloro, bromo, or iodo. The term "triflate" as used herein refers to trifluoromethanesulphonate. The designation "C" as used herein means centigrade. The term "ambient temperature" as used herein means from about 20.degree. C. to about 30.degree. C.
Compounds of the present Invention have 1 or more asymmetric carbon atoms that form enantiomeric arrangements, i.e., "R" and "S" configurations. The present Invention includes all enantiomeric forms and any combinations of these forms. For simplicity, where no specific configuration is depicted in the structural formulas, it is to be understood that both enan
REFERENCES:
patent: 4399276 (1983-08-01), Miyasaka et al.
patent: 4399282 (1983-08-01), Miyasaka et al.
patent: 4413118 (1983-11-01), Roberts et al.
patent: 4473692 (1984-09-01), Miyasaka et al.
patent: 4545880 (1985-10-01), Miyasaka et al.
patent: 4778891 (1988-10-01), Tagawa et al.
patent: 4871855 (1989-10-01), Marko et al.
patent: 4894456 (1990-01-01), Wall et al.
patent: 4943579 (1990-07-01), Vishnuvajjala et al.
patent: 4965364 (1990-10-01), Marko et al.
patent: 4981968 (1991-01-01), Wall et al.
patent: 5049668 (1991-09-01), Wall et al.
patent: 5053512 (1991-10-01), Wani et al.
patent: 5106742 (1992-04-01), Wall et al.
patent: 5122526 (1992-06-01), Wall et al.
patent: 5122606 (1992-06-01), Wani et al.
patent: 5126494 (1992-06-01), Glheany et al.
patent: 5162532 (1992-11-01), Comins et al.
patent: 5180722 (1993-01-01), Wall et al.
patent: 5191082 (1993-03-01), Comins et al.
patent: 5200524 (1993-04-01), Comins et al.
patent: 5212317 (1993-05-01), Comins et al.
patent: 5227380 (1993-07-01), Wall et al.
patent: 5227543 (1993-07-01), Sharpless et al.
patent: 5243050 (1993-09-01), Comins et al.
patent: 5244903 (1993-09-01), Wall et al.
patent: 5247089 (1993-09-01), Comins et al.
patent: 5254690 (1993-10-01), Comins et al.
patent: 5258516 (1993-11-01), Comins et al.
patent: 5260461 (1993-11-01), Hartung et al.
patent: 5264579 (1993-11-01), Comins et al.
patent: 5315007 (1994-05-01), Comins et al.
patent: 5321140 (1994-06-01), Comins et al.
patent: 5342947 (1994-08-01), Lackey et al.
Kirk-Othmer, Encyclopedia of Chem. Technology-4th Ed., vol. 7, pp. 683 and 721, 1993.
R.P. Herzberg, Journal of Medicinal Chemistry, Modification of the hydroxy lactone ring of camptothecin, vol. 32, No. 3, pp. 715-720 (1989).
J.R. Eckardt et al., "Topoisomerase I Inhibitors: Promising Novel Compounds," Contemporary Oncology, 47-60, Jan. 1993.
M.C. Wani, A.W. Nicholas, M.E. Wall, "Plant Antitumor Agents. 28. Resolution of a Key Tricyclic '-f!.increment..sup.6,8 -tetrahydroindolizine: Total Synthesis and Antitumor Activity of 20(S)-and 20(R)-Camptothecin," J. Med. Chem., 2317-2319, v. 30, N. 12 (1987).
W.D. Kingsbury, "The Chemical Rearrangement of Camptothecin to Mappicine Ketone," Tetrahedron Letters, 6847-6850, v. 29, N. 52 (1988).
A. Ejjima, H. Terasawa, M. Sugimori, H. Tagawa, "Asymmetric Synthesis of (S)-Camptothecin.sup.1 ", Tetrahedron Letters, 2639-2640, v. 30, N. 20 (1989).
E. J. Corey, D. Crouse, J. Anderson, "A Total Synthesis of Natural 20 (S-)-Camptothecin", J. Org. Chem., 2140-2141, v. 40, N. 14 (1975).
D. P. Curran and H. Lui, "New 4+1 Radical Annulations. A Formal Total Syntehsis of (.+-.)-Camptothecin", J. Am. Chem. Soc., 5863-5864, 114 (1992).
J. Quick, "A New Route to Pyridones Via Imines of Pyruvic Esters", Tetrahedron Letters, 327-330, N. 4 (1977).
D.E. Berry et al., "Naturally Occurring Inhibitors of Topoisomerase I Mediated DNA Relazation", J. Org. Chem., 420-422, 57 (1992).
T. Sugasawa, T. Toyoda, and K. Sasakura, "A Total Synthesis of dl-Camptothecin", Tetrahedron Letters, 5109-5112, N. 50 (1972).
A.I.Meyers et al., "A Total Synthesis of Camptothecin and Deethyldeoxycamptothecin", J. Org. Chem, 1974-1982, V. 38, N. 11 (1973).
R.A. Earl and K.P.C. Vollhardt, "The Preparation of 2(1H)-Pyridinones and 2,3-Dihydro-5(1H)-indolizinones via Transition Metal Mediated Cocylization of Alkynes and Isocyanates. A Novel Construction of the Antitumor Agent Camptothecin"<J. Org. Chem., 4786-4800, v. 49, N. 25 (1984).
T. Sugasawa, M. Adachi, K. Sasakura, and A. Kitagawa, "Aminohaloborane in Organic Synthesis.2. Simple Synthesis of Indoles and 1-Acyl-3-indolinones Using Specific Ortho .alpha.-Chloroacetylation of Anilines", J. Org. Chem., 578-586, v. 44, N. 4 (1979).
M.C. Wani et al., "Plant Antitumor Agents. 18..sup.1 Synthesis and Biological Activity of Camptothecin Analogues", J. Med. Chem., 554-560, v. 23, N.5 (1980).
M.C. Wani et al., "Plant Antitumor Agents.IX. The Total Synthesis of dl-Camptothecin", J. Am. Chem. Soc., V. 94, N. 10 (1972).
M.C. Wani, A.W. Nicho
Fang Francis Gerard
Lowery Melissa Williams
Xie Shiping
Dentz Bernard
Glaxo Wellcome Inc.
Grassler Frank P.
LandOfFree
Method of removing heavy metal contaminants from organic compoun does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method of removing heavy metal contaminants from organic compoun, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of removing heavy metal contaminants from organic compoun will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1703812