Selenol Protecting Groups in Organic Chemistry: Special Emphasis on Selenocysteine Se-Protection in Solid Phase Peptide Synthesis

Abstract

The appearance of selenium in organic synthesis is relatively rare, and thus examples in the literature pertaining to the masking of its considerable reactivity are similarly uncommon. Greene's Protecting Groups in Organic Synthesis, the standard reference for the state of the art in this arena, offers no entries for selenium protective methodology, in stark comparison to its mention of the great variety of protecting groups germane to its chalcogen cousin sulfur. This scarcity of Se-protection methods makes it no less interesting and pertinent toward the construction of selenium-containing organic systems which do indeed require the iterative blocking and de-blocking of selenol functionalities. A selenium-containing system which is especially relevant is selenocysteine, as its use in Solid Phase Peptide Synthesis requires extensive protection of its selenol side chain. This review will attempt to summarize the current state of understanding with regard to selenium protection protocol in organic synthesis. Moreover, it will provide a special emphasis on selenocysteine side chain protection, comprising both the breadth of functionality used for this purpose as well as methods of deprotection.

Redox Signaling by Reactive Electrophiles and Oxidants

“…(550) The half-life of this adduct was 4–8 h, and reversal required both GSH and thioredoxin 1. (551) Given that selenocysteine-carbon bonds are weaker than carbon-sulfur bonds, the carbon selenium bond is likely a better acceptor of electrons through negative hyperconjugation,(552) and that SeH is more acidic than SH,(553) it is likely that Michael adducts to protein-selenocysteine are shorter lived than protein-cysteine, assuming there are no cross links/additional protein interactions.…”

Unconventional Bifunctional Lewis-Brønsted Acid Activation Mode in Bicyclic Guanidine-Catalyzed Conjugate Addition Reactions

“…Despite being weak conjugate bases, the selected pro-nucleophiles studied here and/or their analogues have been shown to undergo Michael or nucleophilic addition reactions [24,25,26]. Experimental and computational studies of Lewis acid-base adducts by Denmark et al ., indicated that a Lewis base could enhance the catalytic ability of a Lewis acid [27,28].…”

Biohybrid -Se-S- Coupling Reactions of an Amino Acid Derived Seleninate

“…, disulfides) rather than N -substituted thioamides [ 29 ]. The coupled product 14 can be viewed as a reversibly modified nucleoside, since the Se-S bond can potentially be cleaved by reduction [ 30 , 31 ]; 14 can perhaps also serve as a simplified model for a peptide oligonucleotide hybrid.…”