Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Patent
1996-02-29
1998-06-09
Geist, Gary
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
568823, C07C 3508
Patent
active
057636893
DESCRIPTION:
BRIEF SUMMARY
This is the U.S. National Stage Application of PCT/GB94/01940 filed Sep. 7, 1994 now WO95/07253 published Mar. 16, 1995.
TECHNICAL FIELD
The present invention relates to 3-substituted cis-diols and methods for their preparation.
CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims priority from UK patent application 9318564.3 filed Sep. 7, 1993, which is incorporated herein by reference in its entirety.
BACKGROUND OF THE INVENTION
cis-Dihydroxycyclohexadienes are formed as reaction products from the oxidation of aromatic compounds by bacterial aromatic hydrocarbon dioxygenases. This enzymatic reaction proceeds by the insertion of both atoms of molecular oxygen into the aromatic nucleus to form a vicinal cis-dihydrodiol. For substrates such as toluene, ethylbenzene, J. Chem. Soc. Chem Commun., p. 1630, (1991)! the cis-diols formed have been designated enantiomerically pure. These enantiomerically pure cis-diol reaction products constitute a series of highly useful chiral synthons which have two functionally distinguishable double bonds, two distinguishable oxygens and, in most cases, have a single removable or reactive substituent. The utility of these compounds has been demonstrated by numerous research groups. See, for example, the following: Brown and Hudlicky, Organic Synthesis: Theory and Practice, ed. Hudlicky, JAI Press, Greenwich, Conn., vol. 2, 1993, p. 113; Widdowson, et al., Janssen Chimica Acta, 1990, 8:3; Carless, Tetrahedron: Asymm., 1992, p. 795; U.S. Pat. Nos. 5,200,516, 5,306,846; U.S. patent application Ser. Nos. 07/974,057, 07/060,454; the disclosure of these U.S. Patents and Applications is incorporated herein by reference.
To date all of the synthetic work done with chiral, enantiomerically pure cis-diols has been done with compounds having the Formula I, shown below, where R is a substituent other than hydrogen. If the R substituent in a compound of Formula I is hydrogen, then the compound is meso and must be asymmetrically functionalized if it is to be used for chiral synthesis. To date, only cis-diols substituted at the 3 position and of the illustrated absolute configuration have been available for synthesis. ##STR1##
The reason for the lack of availability of enantiomerically pure cis-diols of configurations other than those shown above is due to the regiospecificity of the dioxygenase enzyme commonly used for their synthesis. Chemically, three different substituted vicinal cis-dihydroxycyclohexadiene enantiomeric pairs are possible. They are shown in Scheme 1. ##STR2##
It has been reported in the literature that certain bacteria and the enzymes expressed by certain bacteria oxidize monosubstituted aromatic compounds of the type shown in the Scheme 1. Of the bacteria reported to have this activity, at least seven strains have been reported which al., App. Environ. Microbiol., 57:3156, (1991); Johnston, et al., Enzyme Microb. Technol., 9:706, (1987); Jenkins, et al., Biotech. Bioeng., 29:873, (1987); U.S. Pat. Nos. 4,876,200; 4,927,759 and 4,508,822; EP0253485; and Geary, et al., J. Chem. Soc. Chem. Commun., 1990, p. 204!. Of the chemically possible diol isomers (shown in Scheme 1), only those resulting from oxidation at the 1-2 bond are produced having the structure designated "A." These reaction products have been established to be enantiomerically pure, and have the absolute configuration illustrated.
The nature of the present invention is related to an observation that aromatic dioxygenases, reacting with disubstituted monocyclic aromatic compounds, still show a regiospecificity of dioxygenation, particularly when such dioxygenases are presented (contacted) with a substituted (preferably disubstituted) aromatic compound in which the substituents are non-identical. By "non-identical" it is meant that the two substituents differ in any number of manners, including but not limited to, size, charge, steric hindrance, hydrophobicity, etc., where size is apparently the principal factor controlling the reference point for oxygen insertion. Size of the substituent ca
REFERENCES:
patent: 5306846 (1994-04-01), Hudlicky et al.
Hudlicky et al; Tetrahedron Asymmetry; vol. 3, #2, pp. 217-220, 1992.
Ziffer et al; JACS; 95: 12; pp. 4048-4049, 1973.
Hudlicky et al; JACS; 110: 14; pp. 4735-4741.
Robert et al; Biomed.Environ.Mass.Spectrom.;18(1);pp. 27-47, 1989.
Nakatsu et al; Drug.Metab.Dispos.;11(5);463-70, 1983.
Sigrun et al; Adv.Exp.Med.Biol.;136A(Biol.React.Intermed.2,Chem.Mech.Biol.Eff.Pt.A)387-9 3, 1982.
Robert et al; Toxicol.Environ.Chem.;10(3),225-46, 1985.
Billings etal; Drug.Metab.Dispos.;13(3);287-90, 1985.
Dankovic et al; Mol.Pharmacol.;27(2),287-95, 1985.
Boyd Derek R.
Dalton Howard
Anderson Kirsten A.
Geist Gary
Padmanabhan Sreeni
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