Synthesis of polypyrrolic macrocycles from meso-substituted tripyrrane compounds

A compound of Formula I: ##STR1## wherein: Q represents identical alkyl groups, cycloalkyl groups having from 5 to 7 ring atoms, or aryl or heteroaryl groups having from 5 to 12 ring atoms andR represents identical hydrogen, alkyl, alcohol or carbonyl-containing groups;or a composition containing from 5 to 100 mole % by weight of the compound of Formula I. A novel method for synthesizing the compound of Formula I comprises the steps of:(a) reacting a compound of the formula:Q--CHO or Q--CH(OS)(OS')wherein Q is as defined above and S and S' are independently lower alkyl, an aryl group containing from 5 to 14 ring atoms, and --(CH.sub.2).sub.n -- where n=2-4, with an excess amount of a pyrrole in the presence of a catalytic amount of a strong Lewis or Bronsted acid;(b) removing any unreacted pyrrole or other solvents used by evaporation;(c) removing polymeric materials and removing the corresponding dipyrromethane by-product, leaving the compound of Formula I.

Skip to:  ·  Claims  ·  References Cited  · Patent History  ·  Patent History

Claims

1. A process for making a meso substituted polypyrrolic macrocycle, said process comprising the steps of:

(a) cyclizing a compound of Formula I having two terminal pyrrole rings, each with an unsubstituted.alpha.-position: ##STR21## wherein: one or both groups Q are aryl or heteroaryl groups, wherein if only one Q is an aryl or heteroaryl group, said other Q is an alkyl group or a cycloalkyl group, and each
R represents a hydrogen, alkyl, alcohol or carbonyl-containing group;
with a compound having a formula selected from the group consisting of:
(1) Q--CHO, wherein Q is an alkyl group, a cycloalkyl group, or an aryl or heteroaryl group;
(2) Q--CH(OS)(OS'), wherein Q is an alkyl group, a cycloalkyl group, or an aryl or heteroaryl group; ##STR22## wherein: S and S' are independently lower alkyl, an aryl group containing from 5 to 14 ring atoms, and --(CH.sub.2).sub.n -- where n=2 to 4;
R.sup.1 -R.sup.5 are independently hydrogen, lower alkyl, alcohol or carbonyl-containing groups;
X and X' are groups capable of coupling with the unsubstituted.alpha.-positions of the terminal pyrrole rings of the compound of Formula I;
Z and Z' are independently --N--, >NH, --O-- or a bivalent sulfur atom; and
Y is a direct link, alkylene, pyrrolylene, furanylene, phenylene, thiophenylene, benzylene, or alkylene-pyrrolene-alkylene,
(b) oxidizing the cyclized intermediate to form the corresponding substituted polypyrrolic macrocycle.

2. The process of claim 1 wherein R.sup.1 -R.sup.5 are selected from the group consisting of hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert-butyl, --C.sub.8 H.sub.17, --OCH.sub.3, --O(CH.sub.2 CH.sub.2 O).sub.3 CH.sub.2 CH.sub.3, --CH.sub.2 OH, --(CH.sub.2).sub.4 OH, --O(CH.sub.2).sub.3 OH, --(CH.sub.2).sub.2 COOH, --(CH.sub.2).sub.2 COOCH.sub.3, and --(CH.sub.2).sub.2 COOC.sub.2 H.sub.5.

3. The process of claim 1 wherein Y is selected from the group consisting of a direct link, --CH.sub.2 --, pyrrolene, furanylene, thiophenylene, benzylene and --CH.sub.2 -pyrrolene-CH.sub.2 --.

4. The process of claim 1 wherein X has the formula --CHO or --CHR'--L where R' is H, alkyl or aryl, and L is a leaving group.

5. The process of claim 1 wherein X is selected from the group consisting of --CHO, --CH.sub.2 OH, --CH.sub.2 NH.sub.2, and --CH(Ar)--OH where Ar is aryl having from 5 to 7 ring carbons.

6. The process of claim 1 further comprising, as step (c), purifying the resulting macrocycle.

7. The process of claim 1, wherein said resultant polypyrrolic macrocycle is a 5,10 meso-disubstituted compound.

8. The process of claim 1, wherein the cyclizing in step (a) thereof is performed in the presence of an acid catalyst.

9. The process of claim 1, wherein a single group Q in Formula I is an aryl or heteroaryl group containing from about 5 to about 14 ring atoms.

10. The process of claim 1, wherein a single group Q in Formula I is an alkyl group containing from about 1 to about 18 carbon atoms.

11. The process of claim 1, wherein a single group Q in Formula I is a cycloalkyl group containing from about 5 to 7 carbon atoms.

12. The process of claim 1, wherein both groups Q in Formula I are aryl or heteroaryl, and are identical.

13. The process of claim 1 wherein at least one group Q in formula I is phenyl or pyridinyl having one or more substituents selected from the group consisting of halogen, lower alkyl, lower alkoxy, hydroxy, cyano, nitro, or a carboxylic acid.

14. The process of claim 1 wherein group Q in Q--CHO or Q--CH(OS)(OS') is selected from the group consisting of an aryl or heteroaryl group containing from about 5 to about 14 ring atoms; an alkyl group containing from about 1 to about 18 carbon atoms; and a cycloalkyl group containing from about 5 to 7 carbon atoms.

15. The process of claim 1 wherein each R in Formula I thereof is selected from the group consisting of hydrogen, lower alkyl, an alcohol, a carboxy-containing group, and an amide of the formula --CO--NR'R" wherein R' and R" are each independently hydrogen, alkyl, or aryl.

16. The process of claim 15 wherein all R groups are the same.

17. The process of claim 1 wherein X and X" have the formula --CHO or --CHR'L where R' is hydrogen, alkyl, or aryl, and L is a leaving group readily lost under conditions of acid catalysis.

18. The process of claim 7, wherein both groups Q in Formula I are identical.

Referenced Cited
U.S. Patent Documents
4935498 June 19, 1990 Sessler et al.
5159065 October 27, 1992 Sessler et al.
5162509 November 10, 1992 Sessler et al.
5302714 April 12, 1994 Sessler et al.
Foreign Patent Documents
WO 91/09861 July 1991 WOX
Other references
  • S. Vigmond et al., "Direct Synthesis of Aryldipyrromethanes," Tetrahedron Letters, vol. 35, pp. 2455-2458, 1994. P-Y. Heo et al., "Facile Syntheses of Modified Tripyrranes and Their Application to the Syntheses of Regioisometrically Pure Porphyrin Derivatives", Bulletin of the Korean Chemical Society, 17, pp. 515-520, 1996. Thomas Carrell, "Modellverbindungen zur Unterschung der Primaprozesse in der Photosynthese", Doctoral Dissertation Ruprecht-Karls Universistat, Heidelberg, Germany, 1992. Chemical Abstracts, vol. 125, No. 11, (1996), Abstract No. 142406. Tetrahedron Letter, vol. 37(2), pp. 197-200, "Stepwise Syntheses of Core-Modified, Meso-Substituted Porphyrins". Tetrahedron Letter, vol. 35(16), pp. 2455-2458, "Direct Synthesis of Aryldipyrromethanes". Bauer, V.J. et al., "Sapphyrins: Novel Aromatic Pentapyrrolic Macrocycles," J. Am. Chem. Soc. (1983) 105:6429-6436. Berlin, K. et al., "New Porphyrinoid Macrocycles Containing Pyridine," Angew. Chem. Int. Ed. Engl. (1994) 33(2):219-220. Berlin, K. et al., "Benziporphyrin, a Benzene-Containing, Nonaromatic Porphyrin Analogue," Angew. Chem. Int. Ed. Engl. (1994) 33(12):1246-1247. Broadhurst, M.J. et al., "The Synthesis of 22 .pi.-Electron Macrocycles. Sapphyrins and Related Compounds," Journal of the Chemical Society (1981) 16:2111-2116. Cavaleiro, J.A.S. et al., "An Anomalous Dipyrrole Product from Attempted Synthesis of a Tetraarylporphyrin," J. Org. Chem. (1988) 53:5847-5849. Charriere, R. et al., "The Chemistry of Polyphrins 2..sup.1 Synthesis of Hexaphyrins and Their Metal Complexes," Heterocycles (1993) 36(7):1561-1575. Chmielewski, P.J. et al., "Tetra-p-tolylporphyrin with an Inverted Pyrrole Ring: A Novel Isomer of Porphyrin" Angew. Chem. Int. Ed. Engl. (1994) 33(7):779-781. Chmielewski, P.J. et al., "5,10,15,20-Tetraphenylsapphyrin--Identification of a Pentapyrrolic Expanded Porphyrin in the Rothemund Synthesis," Chem. Eur. J. (1995) 1(1):68-73. Furuta, H. et al., "`N-Confused Porphyrin`: A New Isomer of Tetraphenylporphyrin," J. Am. Chem. Soc. (1994) 116:767-768. Hill, C.L. et al., "Isolation and Characterization of the Principal Kinetic Product in the Preparation of a Sterically Hindered Tetra-arylporphyrin: X-Ray Structure of a Bis(dipyrromethene) Complex of Zinc, Zn.sup.11 (C.sub.22 H.sub.13 Cl.sub.4 N.sub.2).sub.2 .cndot.toluene" J. Chem. Soc., Chem. Commun. (1985):1228-1229. Lee, C-H. et al., "One-Flask Synthesis of Meso-Substituted Dipyrromethanes and Their Application in the Synthesis of Trans-Substituted Porphyrin Building Blocks," Tetrahedron (1994) 50(39):11427-11440. Rexhausen, H. et al., "The Synthesis of a New 22 .pi.-Electron Macrocycle: Pentaphyrin," J. Chem. Soc. Chem. Commun. (1983):275. Sessler, J.L. et al., "Sapphyrins and Heterosapphyrins," Tetrahedron (1992) 48(44):9661-9672. Sessler, J.L. et al., "Synthesis and Crystal Structure of a Novel Tripyrrane-Containing Porphyrinogen-like Macrocycle," . Org. Chem. (1987) 52:4394-4397. Sessler, J.L. et al., "Texaphyrins: Synthesis and Applications," Acc. Chem. Res. (1994) 27:43-50. Sessler, J.L. et al., "A Nonaromatic Expanded Porphyrin Derived from Anthracene--A macrocycle which Unexpectedly Binds Anions", Angew. Chem. Int. Ed. Engl. (1992) 31(4):452-455. Shipps, G., Jr. et al. "New Synthetic Receptors Derived from Porphyrins," Tetrahedron Letters (1994) 35(37):6823-6826. Broadhurst . . . Woodward et al. J.C.S. Perkin I pp. 2111-2116 (1972). Lee et al. Tetrahedron., vol. 50, No. 39, pp. 11427-11440 (1994). Sessler et al. Tetrahedron., vol.48, No. 44, pp. 9661-9672. Sessler et al. Chem. Eur. J., vol. 1, No. 1 Apr. 1995; pp. 56-67.
Patent History
Patent number: 5808054
Type: Grant
Filed: Mar 7, 1996
Date of Patent: Sep 15, 1998
Assignee: QLT PhotoTherapeutics, Inc. (Vancouver)
Inventors: Christian Bruckner (Vancouver), Ross W. Boyle (Colchester), David Dolphin (Vancouver)
Primary Examiner: Mukund J. Shah
Assistant Examiner: Pavanaram K. Sripada
Law Firm: Morrison & Foerster
Application Number: 8/612,215