A semi-synthetic approach to olefinic analogs of amino acid one (MeBMT) in cyclosporin A

✍ Scribed by Sang B. Park; G.Patrick Meier

• Book ID: 104233135
• Publisher: Elsevier Science
• Year: 1989
• Tongue: French
• Weight: 274 KB
• Volume: 30
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(01)80693-6

✦ Synopsis

The syntheses of four olefinic analogs of Cyclosporin A at amino acid one (MeBMT), a residue critical for the Cyclophilin binding domain, are reported. The synthetic process is a rapid, general, semi-synthetic sequence involving oxidative degradation of the olefinic sidechain followed by a Wittig olefination step. Cyclosporin A (CsA) -a cyclic, neutral, hydrophobic undecapeptide -is one of a small class of pharmacologically active agents with selective immunosuppressive activity.1 The immunosuppressive activity of CsA is exhibited in the selective inhibition of clonal expansion of helper and cytotoxic T-cells, with only partial inhibition of the suppressor T-cells. As a result of this selectivity, CsA is currently used clinically for transplantation of kidney, bone marrow, liver, pancreas, heart, lung, and corneas.2 In addition, CsA has been shown to have clinical indications for various autoimmune diseases.3 The ultimate clinical use of CsA is limited, however, primarily due to nephro-and hepatotoxicity.4 Cyclospotfn A (CsA)