N-alpha-(9-Fluorenylmethyloxycarbonyl)-S-tetrahydropyranyl-L-cysteine

Tetrahydropyranyl (Thp), a new S,O-acetal nonaromatic protecting group for cysteine, which has been shown to be superior to Trt, Dpm, Acm, and StBu in solid-phase peptide synthesis using the Fmoc/tBu strategy. Cys racemization and C-terminal 3-(1-piperidinyl)-alanine formation were minimized when the Cys was protected with Thp accompanied by improved solubility of Cys-containing protected peptides. Complete deprotection can be carried out with either TFA/TIS/DCM (10:1.5:88.5) within 5 min or with HCl/dioxane (12:88) in 2h. Reference: Tetrahydropyranyl, a Nonaromatic Acid-Labile Cys Protecting Group for Fmoc Peptide Chemistry; I. Ramos-Tomillero, H. Rodriguez and F. Albericio; Organic Letters 2015; 17: 1680-1683. doi:10.1021/acs.orglett.5b00444