A convergent synthesis of the 11-oxa prostaglandin analogue AL-12182.
[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.
Fox
Martin E
ME
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
Jackson
Mark
M
Lennon
Ian C
IC
McCague
Raymond
R
D003500:Cyclization; D015394:Molecular Structure; D011453:Prostaglandins / Q000737:chemistry; D011465:Prostaglandins, Synthetic / Q000138:chemical synthesis* / Q000737:chemistry
C500274:AL-12182; D011453:Prostaglandins; D011465:Prostaglandins, Synthetic