Diastereoselective synthesis of highly functionalized fluoroalkene dipeptide isosteres and its application to Fmoc-based solid-phase synthesis of a cyclic pentapeptide mimetic

A diastereoselective and divergent method for synthesis of a highly functionalized (Z)-fluoroalkene dipeptide isosteres has been developed. The key feature of this synthetic method is an efficient one-pot reaction involving reduction/asymmetric alkylation via transmetalation, which produces trans-amide type (Z)-fluoroalkenes flanking two stereogenic centers in high yields, with excellent (Z)-selectivity and diastereoselectivity. Practical Fmoc-based solid-phase synthesis of a specific CXCR4 antagonistic pseudopeptide 25 containing (Z)-fluoroalkene isostere is also described.