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(12) United States Patent (73) Assignee: Ls3oard Ofareg US006262257B1 (12) United States Patent (10) Patent N0.: US 6,262,257 B1 Gale et al. (45) Date of Patent: Jul. 17, 2001 (54) CALIXPYRROLES, Andreetti, G., “Crystal and Molecular Structure of CALIXPYRIDINOPYRROLES AND Cyclo{quarter[(5—t—butyl—2—hydroxy—1,3—phenylene)m CALIXPYRIDINES ethylene]} Toluene (1:1) Clathrate,” J. C.S. Chem. Comm., 1005—1007, 1979. (75) InVeIlIOrSI Philip A- Gale; JOIlathaIl L- Sessler; Asfari, et al., “Quick Synthesis of the First Double Porphy JOhIl W- Genge, all Of Austin, TX rin Double Calix[4]arene,” Tetrahedron Letters, vol. 34, No. (US); Vladimir A. Kral, Praha (CZ); 4,119 627428, 1993 Alldl‘ei Andrievsky, Rochester, NY Baeyer, A., “Ueber ein Condensationsproduct von Pyrrol mit (US); Vincent Lynch, Austin, TX (US); Aceton,” Ber Dtsch. Chem. Ges., 19:2184—2185, 1986. Petra I- 831150111, Edgewater, NJ (Us); Beer, et al, “A Neutral Upper to LoWer Rim Linked Bis— William E- Allell, Austin, TX (Us); Calix[4]arene Receptor that Recognises Anionic Guest Spe ChI‘iStOPhEI‘ T- BI‘OWII, Austin, TX cies,” Tetrahedron Letters, vol. 36, No. 5, pp. 767—770, J an., (US); Andreas Gebauer, Austin, TX 1995 _ (Us) Beer, et al., “Anion Recognition by Novel Ruthenium(II) (73) Assignee:_ ls3oard ofAReg'entrskUligiglersity_ _ of Texas SBi 052/ ridCgem l Calix cogmglunw 4 arene 126941271,Rece tor Molecules,”1994' J. Chem. ystem’ usnn’ ( ) Beer, et al., “Anion Recognition by Redox—Responsive ( * ) Notice, Subject to any disclaimer the term of this Ditopic Bis—Cobaltocenium Receptor Molecules Including a patent is extended or adgusted under 35 Novel Calix[4]arene Derivative That Binds a Dicarboxylate U_S_C_ 154(k)) by 0 days_ Dianion, Organometallzcs, 14:3288—3295, Jul., 1995.' ' Beer, et. al., “Structures of Potassium encapsulated Within (21) APPL NO; 08/833,379 the 1,3—Alternate Conformation of Calix[4]arenes,” J. _ Chem. Soc. Dalton Trans., 3479—3485, 1994. (22) Flled: Apr- 4’ 1997 Beer, et al., “Synthesis and Co—ordination Chemistry of a Related US‘ Application Data Novel BIS(B6I1ZO CroWn Ether) Substituted Calix[4]ar’ene (60) Provisional. application. No. 60/033,396, ?led on Dec. 17, that can Simultaneously Complex Cations and Anions, J. 1996, provisional application No. 60/033,395, ?led on Dec. c?lem' SOC‘ Daltonirans'a 3117_3123’ Oct” 1995' 17, 1996, provisional application No. 60/026,694, ?led on Bohrner, V., “Calixarenes, Macrocycles With (Almost) SeP-25, 1996, Provisiona1 application No- 60/024,203, ?led Unlimited Possibilities,” Angew. Chem. Intl. Ed. EngL, on Aug. 27, 1996, and provisional application No. 60/014, 34,713_745 Jul‘ 1995 890’ ?led on Apr' 5’ 1996' Bonar—LaW, R., “Porphyrin Synthesis in Surfactant Solu 7 _ tion: Multicomponent Assembly in Micelles,” J. Org. (51) Int. Cl. ........................ .. C07B 47/00, C07D 487/22 Chem.) 61:3623_3634, Jan.’ 1996. BroWn, et al., “The Condensation of Cyclohexanone With (52) US. Cl. ............................................................ .. 540/145 Furan and pyrrole,” Canadian J‘ of Chem‘) 49: 4017_4022, (58) Field of Search ............................................. .. 540/145 1971' (56) References Cited (List continued on next page.) U.S. PATENT DOCUMENTS Primary Examiner—Robert Gerstl (74) Attorney, Agent, or Firm—Thorpe, North & Western 5,808,059 * 9/1998 Sessler ............................... .. 450/474 LLP FOREIGN PATENT DOCUMENTS (57) ABSTRACT 0 233 701 8/1987 (EP). The present invention provides calixpyrrole, WO 89/08092 9/1989 (WO) . WO 93/13150 calixpyridinopyrrole, and calixpyridine macrocycles, having 7/1993 (WO) . 4, 5, 6, 7, or 8 heterocyclic rings, as Well as syntheses, OTHER PUBLICATIONS derivatives, conjugates, multimers, and solid supports Aoyama, et al., “Multi—Point Interaction of Phosphates With thereof. Such macrocycles have proved to be effective and Protonated Pyridylporphyrin Discrimination of Monoalkyl selective ion- and neutral molecule-binding agents forming and Dialkyl Phosphates,” Chemistry Letters, pp. 1241—1244, supramolecular ensembles, and ion- and neutral molecule 1991. separation agents. The macrocycles are fully meso-non Vogel, et al., “2,7,12,17—Tetraproplyporphycene—Counter hydrogen-substituted porphyrinogens, a feW molecules of part of Octaethylporphyrin in the Porphycene Series,” Which Were previously knoWn but not recognized as pos Angew. Chem. Int. Ed. Engl., 26, No. 9, pp. 928—931, 1987. sessing anion- or molecule-binding properties. The binding Vogel, et al., “NeW Porphycene Ligands: Octaethyl— and mode is noncovalent, primarily that of hydrogen-bonding, Etioporphycene (OEPc and EtioPc)—Tetra — and Pentaco thereby providing a neW mode for liquid chromatography, ordinated Zinc Complexes of OEPc,” Angew. Chem. Intl. that of Hydrogen Bonding Liquid Chromatography. Further Ed. EngL, 32, No. 11, pp. 1600—1604, 1993. useful applications of the macrocycles provided herein Pending Application in India; No. 708/MAS/97 to Gale et al. include environmental remediation by removal of undesired ?led Apr. 3, 1997. ions or neutral molecules, and removal of phosphate for Allen, et al., “Binding of Neutral Substrates by Calix[4] kidney dialysis. pyrroles,” J. Am. Chem. Soc., vol. 118, No. 49, pp. 12471—12472, Sep., 1996. 1 Claim, 30 Drawing Sheets US 6,262,257 B1 Page 2 OTHER PUBLICATIONS Fujimoto, et al., “Synthesis and Crystallographic Studies of a Calix[4]arene With a 1,3—Alternate Conformation,” J. ChelintZev, B., and Tronov, V., “Simple condensation of Chem. Soc., Perkin Trans. 2, pp. 643—648, 1992. pyrrole With methyethyl ketone and methylhexyl ketone, Gale, et al., “Calix[4]pyrroles: C—rim substitution and tun mixed condensation With acetone and methyethyl ketone, ability of anion binding strength,” Chem. Commun., pp. and relation of these reactions to the determination of the 665—666, 1997. formulas of chlorophyll and hemin,” J. Russian Physical Gale, et al., “Calix[4]pyrroles: Old Yet NeW Anion—binding Chem. Soc., 48:1197—1209, 1916, Chemical Abstracts only, Agents,” J. Am. Chem. Soc., vol. 118, No. 21, pp. p. 1418. 5140—5141, Jan., 1996. ChelintZev, V.V., and Tronov, B.V., “Process of condensation Gale, et al., “Calixprroles: old yet neW anion binding of pyrrole and acetone. Constitution of the resulting prod agents,” 31“ Int’l Conf. on Coordination Chemistry, Uni ucts,” J. Russian Physical Chem. Soc., 48:105—155, 1916, versity of British Columbia, Vancouver, Canada, Aug. 18, Chemical Abstracts only, pp. 452—454. 1996. Chen, et al., “Synthesis and electrochemical polymeriZation Gale, et al., “New Applications for Calixpyrroles,” Royal of calix[4]arenes containing N—substituted pyrrole moi Soc. Chem. U.K. Macrocycles Group Annual General Mtg, eties,” J. Electroanalytical Chem., 393: 113—117, Aug., University of Wales, Cardiff, Wales, UK, Dec. 18, 1996. 1995 . Gale, et al., “Synthesis of a NeW Cylindrical Calix[4] CrescenZi, et al., “The NZO2 porphyrinogen skeleton: arene—Calix[4]pyrrole Pseudo Dimer,” Tetrahedron Letters, Access to a novel class of coordinatively unsaturated tran vol. 37, No. 44, pp. 7881—7884, Sep., 1996. sition metal ions,” Inorganic Chem., 35:2413—2414, Apr., Ghidini, et al., “Complexation of Alkai Metal Cations by 1996. Conformationally Rigid, Stereoisomeric Calix[4]arene DeAngelis, et al., “A Li2Ti2—substituted acetylene formed CroWn Ethers: A Quantitative Evaluation of PreorganiZa from ethylene by reaction With (meso— octaethyl porphy tion,” J. Am. Chem. Soc., 112:6979—6985, 1990. rinogen) titanium,” Angewante Chemie, International Edi Golder, et al., “5,10,15,20—meso—tetrakis(3, tion, English, 34:1092—1094, Jun., 1995. 5—di—t—butyl—4—quinomethide)porphyrinogen: a highly De Angelis, et al., “Solvent—dependent Forms of Lithiated puckered tetrapyrrolic macrocycle from the facile aerial 5,5,10,10,15,15,20,20—Octaethylporphyrinogen in Solution oxidation of a phenolic porphyrin,” J. Chem. Soc., Chemical and in the Solid State and Reaction With Tetrahydrofuran,” Communications, 1751—1753, 1989. J. Chem. Soc., Dalton Trans., 2467—2469, 1994. IsoZ, et al., “Niobium—carbon functionalities supported by DeAngelis, et al., “Organometallic chemistry of a titanium meso—octaethylporphyrinogen and derived macrocycles,” (IV) meso—octaethylporphyrinogen complex: Carrier prop Organometallics, 15, 337—344, Jan., 1996. erties of polar organometallics and their behavior in inser J acoby, et al., “Bifunctional carriers of organometallic func tion reactions,” Organometallics, 14:4505—4512, Oct., tionalities: alkali—metal—Zirconium—hydrido, —alkyl, and 1995 . —allyl derivatives of meso—octaethylporphyrinogen and their DeAngelis, et al., “Oxidation of metal—meso—octaethylpor reaction With isocyanides,” Organometallics, phyrinogen complexes leading to novel oxidiZed forms of 14:4816—4824, Oct., 1995. porphyrinogen other than porhyrins. 2. The redox chemistry Jacoby, et al., “Electrophilic activation of aliphatic C—H of iron (II)— and cobalt (II)—meso—octaethylporphyrinogen bonds mediated by Zirconium hydride entities and applied to complexes occurring With the formation and cleavage of tWo the functionaliZation of the porphyrinogen periphery,” J. cyclopropane units,” J. Am. Chem. Soc., 116:5702—5713, Amer. Chem. Soc., 117:2805—2816, Mar., 1995. 1994. Jacoby, et al., “Macrocyclic modi?cation using organome DeAngelis, et al., “Oxidation of metal—meso—octaethylpor tallic methodologies. Regiochemically controlled mono— phyrinogen complexes leading to novel oxidiZed forms of and bis—homologation reactions of porphyrinogen With car porphyrinogen other than porphyrins. 1. The redox chemis bon monoxide assisted by early
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