Improved synthetic routes to the selenocysteine derivatives useful for Boc-based peptide synthesis with benzylic protection on the selenium atom

Abstract

Selenocysteine (Sec) derivatives, i.e., Boc-Sec(MBn)-OH (1) and Boc-Sec(MPM)-OH (2), which are useful for chemical synthesis of selenopeptides, were obtained from L-serine in five steps with total yields of 73% and 74%, respectively. The enantiomeric excesses were confirmed to be >99% e.e. by optical resolution using a chiral column on HPLC. On the other hand, for the case of a Fmoc-protected Sec derivative, i.e., FmocSec(MPM)-OH, similar reactions resulted in low yields and partial racemization taking place.

Seleno-relaxin analogues: effect of internal and external diselenide bonds on the foldability and a fibrosis-related factor of endometriotic stromal cells

“…As with peptides 1 and 2, selenopeptides 3 and 4 were synthesized by the SPPS method based on the N , N ’-dicyclohexylcarbodiimide (DCC)-hydroxybenzotriazole (HOBt) coupling system. Note that for coupling of the Sec derivative (Fmoc-Sec[MPM]-OH), 70 diisopropylcarbodiimide (DIC) was used as a condensing agent instead of DCC based on our previous method. 64 The resulting selenopeptides attached to the resin were then treated with a trifluoroacetic acid-based cocktail containing 2,2′-dipyridyldisulfide, which is a capping-reagent for SH and SeH groups, to remove protecting groups and the resin.…”

Strategies for the Synthesis of Selenocysteine Derivatives

“…It is important to note that the same strategy is not applicable for the synthesis of Fmoc derivatives. 18 Following the disconnection 'a', in 2010 Chandrasekaran and co-workers developed a new methodology to obtain selenocystine derivatives based on the regioselective ringopening of sulfamidates derived from -hydroxy--amino acids using a sequential, one-pot strategy. 19 Indeed, cyclic sulfamidates 12 derived from L-Ser, L-threonine (Thr), or racemic -phenylserine were treated with KSeCN in acetone to give the corresponding selenocyanates by regioselective Se-nucleophilic ring-opening reaction.…”

Decarboxylative ring-opening of 2-oxazolidinones: a facile and modular synthesis of β-chalcogen amines

“… 10 However, the structural variety commercially available for 2-haloethylamines is relatively limited, particularly regarding optically active substrates. β-Amino alcohols can also be used as starting materials for the synthesis of β-CAs, 11 but they require the use of protecting groups which is a disadvantage. While regioselective aminochalcogenation of alkenes has been shown to be a promising alternative for the synthesis of β-CAs, most reports are still limited to the use of soft-conjugated nitrogenous nucleophiles.…”