Synthesis and Biological Evaluation of Apicularen A Analogues

✍ Scribed by Andreas F. Petri; Florenz Sasse; Martin E. Maier

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 194 KB
• Volume: 2005
• Category: Article
• ISSN: 1434-193X
• DOI: 10.1002/ejoc.200400838

✦ Synopsis

Abstract

Reactions between amide anions and propanal derivatives containing benzolactone components at their 3‐positions produced hemiaminals, which were dehydrated via the corresponding acetates to provide the apicularen A analogues 21, 29, 34, 38, and 41. Of these, 21 and 29 contain the intact enamide side chain of apicularen A but have modifications in the macrolactone core. On the other hand, compounds 34, 38, and 41 are characterized by the natural core structure but are modified in the enamide part. Biological studies showed that 21 and 29 are quite active but that the other three analogues show only minor activities. The 11‐deoxy analogue 21 turned out to be the most active compound against a mdr cell line. It can be concluded that the macrolactone part of apicularen A will tolerate modifications to some degree, whereas the enamide part is rather sensitive towards structural modifications. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)