S-Fluorenylmethyl protection of the cysteine side chain upon N α-Fmoc deprotection
نویسندگان
چکیده
Deprotection of an N(α)-Fmoc-protected glycocysteine derivative 7 with an excess of morpholine unexpectedly led to the fluorenylmethyl-protected thioether 8 in high yield. The suggested mechanism for this reaction comprises the addition of the cysteine thiolate on the exocyclic double bond of dibenzofulvene, which is formed during Fmoc deprotection. The influence of base concentration on this transprotection reaction was studied.
منابع مشابه
Cysteine Pseudoprolines for Thiol Protection and Peptide Macrocyclization Enhancement in Fmoc-Based Solid-Phase Peptide Synthesis
Contrary to other studies, here we describe cysteine (Cys) pseudoproline-containing peptides with short deprotection times in TFA. The deprotection times fell in the same range as other protecting groups commonly used in SPPS (e.g., 1-3 h). Moreover, when using Cys pseudoprolines as peptide macrocyclization-enhancing moieties a considerable reduction in reaction time was observed compared to a ...
متن کاملDBU-catalyzed transprotection of N-Fmoc-cysteine di- and tripeptides into S-Fm-cysteine di- and tripeptides.
The transprotection of N-Fmoc-cysteine containing di- and tripeptides possessing a free SH group to produce the corresponding S-Fm-cysteine di- and tripeptides bearing a free amino group is accomplished efficiently with DBU in dry THF. The N-Fmoc to S-Fm transformation mechanism is discussed. S-Fm-Cysteine di- and tripeptides readily form amide bonds on coupling with N-(Pg-α-aminoacyl)benzotria...
متن کاملSolid-phase synthesis of cyclic peptide chitinase inhibitors: SAR of the argifin scaffold† †Electronic supplementary information (ESI) available: ES-MS data for compounds 10a and 10b. See DOI: 10.1039/b815077j Click here for additional data file.
A new, highly efficient, all-solid-phase synthesis of argifin, a natural product cyclic pentapeptide chitinase inhibitor, is reported. The synthesis features attachment of an orthogonally protected Asp residue to the solid support and assembly of the linear peptide chain by Fmoc SPPS prior to cyclisation and side-chain manipulation on-resin. Introduction of the key N-methyl carbamoyl-substitute...
متن کاملTrimethoxyphenylthio as a Highly Labile Replacement for <italic>tert</italic>-Butylthio Cysteine Protection in Fmoc Solid Phase Synthesis
Trimethoxyphenylthio (S-Tmp) is described as a novel cysteine protecting group in Fmoc solid phase peptide synthesis replacing the difficult to remove tert-butylthio. S-Tmp and dimethoxyphenylthio (S-Dmp) were successfully used for cysteine protection in a variety of peptides. Moreover, both groups can be removed in 5min withmild reducing agents. S-Tmp is recommended for cysteine protection, as...
متن کاملEfficient asymmetric synthesis of (S)- and (R)-N-Fmoc-S-trityl-alpha-methylcysteine using camphorsultam as a chiral auxiliary.
(1R)-(+)-2,10- and (1S)-(-)-2,10-camphorsultam were acylated with ethyl 2-phenylthiazoline 4-carboxylate to afford (+)- and (-)-2-phenylthiazolinylcamphorsultam, which were stereoselectively alkylated with MeI in the presence of n-BuLi. Alkylation of these phenylthiazolinylcamphorsultams occurred from the beta-face rather than alpha-face, resulting in the formation of (S)-alpha-methylcysteine f...
متن کامل