The enantioselective synthesis and antiinflammatory activity of novel aryl-sphingolipid PKC inhibitors

✍ Scribed by Gregory Merriman; John J. Tegeler; R.Richard L. Hamer; Barbara S. Rauckman; Brian S. Freed; Ellen S. Kurtz; Steven C. Bailey; Marie Ortega-Nanos; Penelope A. Przekop; Luther Hellyer

• Book ID: 103983119
• Publisher: Elsevier Science
• Year: 1995
• Tongue: English
• Weight: 273 KB
• Volume: 5
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/0960-894x(95)00428-v

✦ Synopsis

Recently we identified three promising topically active antiinflammatory agents (2, 3, and 4) from a series of racemic aryl-sphingolipids that inhibit protein kinase C (PKC). We now wish to report the enantioselective synthesis of the aforementioned leads and their comparative biological profile. The individual enantiomers examined are equipotent to their racemate in vitro and in vivo. * (+)-2 (11) was prepared using (+)-DIPT in the Sharpless epoxidation 7 -* 8 ** Epoxide 8 was analyzed by chiral HPLC using a Chiralcel OD column.

Unfortunately, the Sharpless epoxidation methodology failed when applied to the synthesis of the corresponding thiophene analogs. As a result we employed chiral oxazolidinone technology to prepare the