title: A convergent synthesis of the 11-oxa prostaglandin analogue AL-12182.
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.
authors.affiliation: Dowpharma, Chirotech Technology Ltd., A subsidiary of the Dow Chemical Company, U321 Cambridge Science Park, Milton Road, Cambridge, CB4 0WG, United Kingdom. mfox@dow.com
authors.forename: Martin E
authors.initials: ME
authors.lastname: Fox
authors.forename: Mark
authors.initials: M
authors.lastname: Jackson
authors.forename: Ian C
authors.initials: IC
authors.lastname: Lennon
authors.forename: Raymond
authors.initials: R
authors.lastname: McCague
mesh_terms: D003500:Cyclization; D015394:Molecular Structure; D011453:Prostaglandins / Q000737:chemistry; D011465:Prostaglandins, Synthetic / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C500274:AL-12182; D011453:Prostaglandins; D011465:Prostaglandins, Synthetic