An Efficient Stereoselective Total Synthesis of dl-Sesquicillin, a Glucocorticoid Antagonist

✍ Scribed by Fei Zhang; Samuel J. Danishefsky

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 102 KB
• Volume: 41
• Category: Article
• ISSN: 0044-8249
• DOI: 10.1002/1521-3773(20020415)41:8<1434::aid-anie1434>3.0.co;2-a

✦ Synopsis

Sesquicillin is a C29 isoprenoid-related fermentation product isolated from Acremonium sp., strain 132-94. [1] The compound was first identified through screenings directed at the discovery of new agents that inhibit glucocorticoidinduced gene expression in suitably engineered COS-7 cells (IC 50 0.1 ± 0.5 mg). In principle, sesquicillin could function as a glucocorticoid antagonist. [2] Also, antihypertensive and bronchospasmolytic properties have been ascribed to sesquicillin in patent disclosures. [3] It is only relatively recently that the gross structure and stereochemistry of sesquicillin have been assigned to be 1, largely on the basis of detailed NMR spectroscopic measurements. As such, sesquicillin bears a striking resemblance to subglutinols A and B. [4] We hoped that a total synthesis of sesquicillin would allow access to the natural product and its analogues. In this way, we could begin to evaluate the potential of this particular type of glucocorticoid antagonist in projected applications.