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A convergent synthesis of the 11-oxa prostaglandin analogue AL-12182
Martin E Fox1, Mark Jackson, Ian C Lennon
1Dowpharma, Chirotech Technology Ltd., A subsidiary of the Dow Chemical Company, U321 Cambridge Science Park, Milton Road, Cambridge, CB4 0WG, United Kingdom. mfox@dow.com
Abstract:
[reaction: see text] The 11-oxa prostaglandin analogue AL-12182 1 has potent topical ocular hypotensive activity. A convergent and concise general synthesis of this class of prostanoid was developed employing a stereoselective coupling reaction between a tetrahydrofuran core electrophile and a nucleophilic omega side chain component, providing a route that should be suitable for commercial scale production. The tetrahydrofuran core was assembled from dimethyl d-malate using a stereoselective beta-hydroxy ester dianion alkylation reaction.
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