PROSTAGLANDIN SYNTHESIS

摘要

A process for the preparation of a compound of formula (I) wherein X and X' each represents hydrogen or together represent a bridging group -CH2-, -CH2-CH2- or -O-; R<1> is a 6-carboxyhex-2-enyl group or a modification thereof in which the group is altered by one, or an appropriate combination of two of more, of the following: (a) alteration of the position of the double bond, with the proviso that in the modified group the double bond is not in the alpha-beta position relative to the ring; (b) reduction of the double bond; (c) alteration of the chain length through a decrease of one or two methylene groups or an increase of one to six methylene groups; (d) replacement of one or two methylene groups each separately by an oxygen or sulphur atom, with the proviso that in the modified group no oxygen or sulphur atom is in an alpha position relative to either a doubly bonded carbon atom or to the carboxy group or a derivative thereof and that at least 2 carbon atoms separate any pair of oxygen and/or sulphur atoms; and (e) formation of an amide, ester or salt derivative of the carboxy group; R<2> is an aliphatic hydrocarbon group or an aliphatic hydrocarbon group substituted by an aromatic group directly or through an oxygen or sulphur atom; and R<3>, R<4>, R<5> and R<6> are each hydrogen, or R<3> and R<4> together and/or R<5> and R<6> together represent the second bond of a carbon-carbon double bond; comprises effecting a Diels Alder reaction between a diene of formula (II) and a dienophile of formula (III) wherein X, X' and R<2> are as defined for (I); Y is R<1> or a precursor therefor in which a double bond is present and/or the terminal group is in different form, either being a free carboxy group rather than the carboxy group derivative present in R<1> or being a carboxy group derivative rather than the free carboxy group present in R<1>; and R and R' are either each hydrogen or together represent the third bond of a carbon-carbon triple bond; and where appropriate thereafter, in either order, reducing the double bond or bonds in the ring of the Diels Alder adduct and/or converting the group Y to the group R<1>. The compounds prepared by this process are of value as intermediates for the preparation of biologically active compounds.