Synthesis of some monocyclic analogues of mycophenolic acid via the Johnson ortho ester Claisen rearrangement

• Published in: Bioorganic & medicinal chemistry 2005-12, Vol.13 (23), p.6521-6528
• Main Authors: Meza-Aviña, Ma Elena, Ordoñez, Mario, Fernández-Zertuche, Mario, Rodríguez-Fragoso, Lourdes, Reyes-Esparza, Jorge, Martínez de los Ríos-Corsino, Abril A.
• Format: Article
• Language: English
• Subjects: Cell Line; Cell Survival - drug effects; Chemistry; Claisen–Johnson rearrangement; Cyclization; Esters - chemistry; Exact sciences and technology; Humans; Molecular Structure; Mycophenolic acid; Mycophenolic Acid - analogs & derivatives; Mycophenolic Acid - chemical synthesis; Mycophenolic Acid - chemistry; Mycophenolic Acid - toxicity; Noncondensed benzenic compounds; Organic chemistry; Ortho esters; Preparations and properties
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2005.07.013

The synthetic methodology reported here allows the preparation of mycophenolic acid analogues bearing alkyl substituents at the α- and β-positions on the side chain. The synthesis of some monocyclic analogues of mycophenolic acid in which the lactone ring has been eliminated, leaving the aromatic ring intact and the same oxygenated substituents flanking the hexenoic acid side chain with an ( E)-geometry at the double bond, has been accomplished via the Johnson ortho ester Claisen rearrangement. The synthetic methodology reported here allows the preparation of mycophenolic acid analogues bearing alkyl substituents at the α- and β-positions on the side chain.