Two new improved approaches to the synthesis of coumarin-based prodrugs

✍ Scribed by Ailian Zheng; Wei Wang; Huijuan Zhang; Binghe Wang

• Publisher: Elsevier Science
• Year: 1999
• Tongue: French
• Weight: 1008 KB
• Volume: 55
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(99)00121-0

✦ Synopsis

Our laboratory has recently reported the development of a conmarin-based, esterase-sensifive prodrug system for the preparation of prodrugs of amines, peptides, and peptidomimetics. Biological evaluations including animal studies have demonstrated the clinical potential of this prodrug system. However, the original synthetic method used required a long sequence of reactions with a relatively low overall yield. In this report, we describe two new approaches to the synthesis of these coumarin-based prodrugs. The first approach is a photochemical approach taking advantage of the photoisomerizatinn of cinnamic acid and its derivatives. The second approach is through the catalytic hydrogenation of a triple bond for the generation of the c/s double bond in the coumarinic acid moiety. Both approaches allow for the synthesis of these prodrogs in fewer steps with much improved overall yield.