Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2002-08-26
2003-09-16
Dentz, Bernard (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C549S051000, C549S058000, C549S404000, C549S405000, C549S407000, C549S462000, C549S471000, C549S475000, C548S470000, C548S492000, C548S494000, C548S509000, C546S141000, C546S146000, C546S168000, C546S174000, C546S179000
Reexamination Certificate
active
06620947
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to novel compounds and processes useful in the synthesis of certain prostaglandin analogs. Specifically, the invention relates to intermediates and processes useful in the synthesis of certain 11-oxa prostaglandins.
BACKGROUND OF THE INVENTION
Substituted tetrahydrofuran analogs of D and F series prostaglandins for use in treating glaucoma and ocular hypertension are disclosed in commonly assigned U.S. Pat. No. 5,994,397, the entire contents of which are by this reference incorporated herein. 11-oxa PGF
2a
analogs and/or synthetic schemes for their preparation are is disclosed in Hanessian, et al., Carbohydrate Research, 141:221-238 (1985); Thiem et al., Liebigs Ann. Chem., 2151-2164 (1985); Arndt, et al., S. African J. Chem. 34:121-127 (1981); and U.S. Pat. No. 4,133,817. The entire contents of these references are hereby incorporated herein.
Previous routes to 11-oxa prostaglandins employ a C1-C2 olefination reaction of a tetrahydrofiiran-2-carboxaldehyde for the introduction of the &ohgr;-chain. The &agr;-chain may be introduced before or after this step. The tetrahydrofuran-2-carboxaldehyde may be prepared from several readily available carbohydrates, which provide the four carbons of the tetrahydrofuran core and C1 of the &ohgr;-chain. The following carbohydrates have been used as starting materials in this approach: D-sorbitol (J. Thiem and H. Lüders, Liebigs Ann. Chem., 2151 (1985) and S. Hanessian, Y. Guindon, P. Lavallée and P. Dextraze, Carbohydrate Research, 141, 221 (1985)), D-xylose and D-glucose (G. J. Lourens and J. M. Koekemoer, Tetrahedron Letters, 43:3719 (1975) and R. R. Arndt, J. M. Koekemoer, G. J. Lourens and E. M. Venter, S.-Afri. Tydskr. Chem., 34:121 (1981)).
It is desirable, especially to improve therapeutic effect, to isolate the active isomer of the desired compound. In order for development of a pharmaceutical product comprising the enantiomerically enriched compound to be feasible, an economically viable synthetic route that will yield commercial quantities of the material is required.
Previously known syntheses of 11-oxa prostaglandins have suffered from various drawbacks that limit their usefulness for production of commercial quantities of the desired material. Such drawbacks include, without limitation, low yields, costly, time consuming, or inefficient synthetic sequences, and/or difficult or inadequate separation of the undesired enantiomer or epimer. A need exists, therefore, for an improved, commercially viable synthetic approach for. 11-oxa prostaglandin analogs.
SUMMARY OF THE INVENTION
The present invention is directed to novel processes and intermediates useful in the preparation of preferred enantiomers of certain 11-oxa prostaglandins. The processes and intermediates of the present invention are particularly useful in the preparation of [2R(1E,3R),3S(4Z),4R]-7-[Tetrahydro-2-[4-(3-chlorophenoxy)-3-hydroxy-1-butenyl]-4-hydroxy-3-furanyl]-4-heptenoic acid and its C1 esters.
REFERENCES:
patent: 4133817 (1979-01-01), Lourens et al.
patent: 5994397 (1999-11-01), Selliah et al.
Arndt et al., “Stereospecific Synthesis of Modified Prostaglandins Derived from Carbohydrates. Part 1.,”S. Afr. J. Chem.34(4):121-127 (Jun. 1981).
Caballcro et al., “Synthesis and Diels-Alder Reactivity of simple 1-Phenoxy-1,3-Dienes,”Tetrahedron Letters37(38):6951-6954 (1996).
Duclos et al., “A Simple Conversion of Polyols into Anhydroalditols,”Synthesispps. 1087-1090 (Oct. 1994).
Hanessian et al., “Total Synthesis of 11-Oxaprostaglandin F2&agr;and F2&bgr;,”Carbohydrate Research141(2):221-238 XP000644751 (1985).
Lourens et al., “The Novel Stereospecific Synthesis of 11-oxapros-taglandin F2&agr;,”Tetrahedron Letters, No. 43:3719-3722 Pergamon Press (1975).
Thiem et al., “Synthese von oxaprostaglandinen aus 1,4:3,6-Dianhydro-D-sorbit,”Liebigs Ann. Chem.2151:2164 XP0006444761 (1985).
Conrow Raymond E.
Dean William D.
Delgado Pete
Gaines Michael S.
Alcon Inc.
Copeland Barry L.
Dentz Bernard
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