tailieunhanh - Modifications of total synthesis of mycophenolic acid

The total synthesis of mycophenolic acid (MPA), a potent immunosuppressant, was modified. The obtained mycophenolic acid was suitable for further preparation of new prospective immunosuppressants with improved therapeutic properties. | Modifications of total synthesis of mycophenolic acid Current Chemistry Letters 7 2018 9 16 Contents lists available at GrowingScience Current Chemistry Letters homepage Modifications of total synthesis of mycophenolic acid Grzegorz Cholewinski Magdalena Malachowska Ugarte Agnieszka Siebert Michał Prejs and Krystyna Dzierzbicka Department of Organic Chemistry Gdansk University of Technology str G. Narutowicza 11 12 80-233 Gdansk Poland CHRONICLE ABSTRACT Article history The total synthesis of mycophenolic acid MPA a potent immunosuppressant was modified. Received November 14 2016 The obtained mycophenolic acid was suitable for further preparation of new prospective Received in revised form immunosuppressants with improved therapeutic properties. January 10 2018 Accepted January 12 2018 Available online January 12 2018 Keywords Mycophenolic acid Immunosuppressants Claisen rearrangement Oxidation Total synthesis 2018 Growing Science Ltd. All rights reserved. 1. Introduction Mycophenolic acid MPA is an immunosuppressive drug widely applied in prophylaxis of organ transplant However the risks of rejection and side effects in the course of clinical treatment were not eliminated. As a result numerous MPA modifications together with their biological evaluations were Although MPA is produced in industrial scale via fermentation processes 19 its price for laboratory scale is still high. In the chemical literature are described attempts of total synthetic MPA from commercially available substrates. Some of them enable to prepare MPA analogs which are difficult to obtain by a modification of starting MPA molecule since the structure of target derivative can be altered at the relevant synthetic stages. In our research we decided to prepare some new MPA derivatives for examination of their immunosuppressive activity. For this purpose we choose Patterson s synthetic strategy as the most convenient one for obtaining of MPA in .