Process for the preparation of 11-oxaprostaglandins and intermediates therein
AssigneeChirotech Technology Limited
InventorsMartin Edward Fox, Mark Jackson
Life of this patent
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Abstract
For the preparation of an 11-oxaprostaglandin such as [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 ester derivatives, a novel process uses a novel enantiomerically enriched compound for formula (1) wherein the bond between carbon atoms y and z is either a single or double bond; R1 is selected from vinyl, trialkylsilylethynyl, a formyl group protected as an acetal, or a protected hydroxymethyl group; R2 is C1-5 alkyl, optionally substituted at the terminus with an aryloxy or alkoxy group; and R3-R6 are independently selected from C1-6 alkyl and C6-10 aryl. 1
Claims19
An enantiomerically enriched compound of formula 1
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- wherein the bond between carbon atoms y and z is either a single or double bond;
- R1 is selected from vinyl, trialkylsilylethynyl, a formyl group protected as an acetal, or a protected hydroxymethyl group;
- R2 is C1-5alkyl, optionally substituted at the terminus with an aryloxy or alkoxy group;
- and R3—R6 are independently selected from C1-6 alkyl and Cr6-10 aryl.
A compound according to any preceding claim, wherein R2 is aryloxymethyl.
A compound according to any preceding claim, wherein R3═R5=methyl and R4═R6=tert-butyl.
A compound according to any preceding claim, wherein the enantiomeric enrichment is at least 95%.
A process for the preparation of a compound of any preceding claim, which comprises the sequential reaction of a silyl acetal of formula 2, wherein R7 is C1-6 n-alkyl, with a trimethylsilyl bromide or iodide, and an organometallic derivative of an alkenyl or alkyl halide of formula 4, wherein X is a halide.
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A process for the preparation of a silyl acetal of formula 2 from a lactone of formula 5, comprising reduction followed by silylation of the resultant lactol wherein the 2 is formed in a ratio of at least 4:1 relative to the silylated hydroxyaldehyde 8.
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An enantiomerically enriched silyl acetal of formula 2.
An enantiomerically enriched lactone of formula 5.
Dependencies are inferred from the claim text.