By oxidation of cyclosporin D (I) with N-chlorosuccinimide (II) and dimethylsulfide in toluene.
Reaction of the labeled chiral bromoacetylbornanesultam (I) with benzophenone imine (II) and DIEA in hot acetonitrile gives the imine (III), which is enantioselectively alkylated with isopropyl iodide and n-BuLi yielding the L-valine derivative (IV). Treatment of (IV) with HCl in THF in order to eliminate the diphenylmethylene group affords compound (V) with a free amino group that by protection with Boc2O in THF provides the L-valine derivative (VI). The hydrolysis of (VI) with LiOH in THF/water affords labeled N-(tert-butoxycarbonyl)-L-valine (VII), which is condensed with the decapeptide (VIII) by means of BOP and NMM in dichloromethane providing the linear undecapeptide (IX).
The reaction of (IX) first with NaOH in ethanol to hydrolyze the terminal ester group, and then with TFA to eliminate the terminal tert-butoxycarbonyl group gives the fully deprotected peptide (X), which is cyclized by means of BOP and NMM in dichloromethane yielding the cyclic peptide (XI). Finally, this compound is oxidized by the modified Pfitzer-Moffat method with DMSO and DCC in tert-butyl methyl ether.