Synthesis of l-Selenocysteine and α-Methyl-l-Selenocysteine Derivatives Using Woollins’ Reagent and Their Application as Chiral Selenium Catalysts

Iwaoka, Michio; Ito, Shun; Miyazaki, Izumo; Michibata, Momoko

doi:10.1007/s40010-016-0307-8

Cited by 6 publications

(3 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because of the quaternary α‐carbon, (αMe)Sec has proven challenging to synthesize. Previously, a racemic pathway by Reich and a chiral pathway by Iwaoka have been executed for the synthesis of (αMe)Sec; however, each has their limitations. Our synthetic method allows for quick synthesis with moderate yields while also obtaining high enantiomeric excess.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis of alpha‐methyl selenocysteine and its utilization as a glutathione peroxidase mimic

Wehrle

Ste.Marie

Hondal

et al. 2019

Journal of Peptide Science

View full text Add to dashboard Cite

Selenocysteine (Sec) is the 21st amino acid in the genetic code where this amino acid is primarily involved in redox reactions in enzymes because of its high reactivity toward oxygen and related reactive oxygen species. Sec has found wide utility in synthetic peptides, especially as a replacement for cysteine. One limitation of using Sec in synthetic peptides is that it can undergo β‐syn elimination reactions after oxidation, rendering the peptide inactive due to loss of selenium. This limitation can be overcome by substituting Cα‐H with a methyl group. The resulting Sec derivative is α‐methylselenocysteine ((αMe)Sec). Here, we present a new strategy for the synthesis of (αMe)Sec by alkylation of an achiral methyl malonate through the use of a selenium‐containing alkylating agent synthesized in the presence of dichloromethane. The seleno‐malonate was then subjected to an enzymatic hydrolysis utilizing pig liver esterase followed by a Curtius rearrangement producing a protected derivative of (αMe)Sec that could be used in solid‐phase peptide synthesis. We then synthesized two peptides: one containing Sec and the other containing (αMe)Sec, based on the sequence of glutathione peroxidase. This is the first reported incorporation of (αMe)Sec into a peptide as well as the first reported biochemical application of this unique amino acid. The (αMe)Sec‐containing peptide had superior stability as it could not undergo β‐syn elimination and it also avoided cleavage of the peptide backbone, which we surprisingly found to be the case for the Sec‐containing peptide when it was incubated for 96 hours in oxygenated buffer at pH 8.0.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Because of the quaternary α-carbon, (αMe)Sec has proven challenging to synthesize. Previously, a racemic pathway by Reich 31 and a chiral pathway by Iwaoka 32,33 have been executed for the synthesis of (αMe)Sec;…”

Section: Resultsmentioning

confidence: 99%

Synthesis of alpha‐methyl selenocysteine and its utilization as a glutathione peroxidase mimic

Wehrle

Ste.Marie

Hondal

et al. 2019

Journal of Peptide Science

View full text Add to dashboard Cite

show abstract

“…Moreover, Iwaoka et al recently described the stereoselective preparation of selenocystine derivatives using Woollins' reagent [173]. These compounds are particularly interesting for application in organic catalysis: Santi et al reported the asymmetric dihydroxylation and hydroxymethoxylation of alkenes catalyzed by Lselenocystine [174].…”

Section: Other Classes Of Diselenides: Towards Macromolecular Gpx Mimicsmentioning

confidence: 99%

Organodiselenides: Organic Catalysis and Drug Design Learning from Glutathione Peroxidase

Tiezza¹,

Ribaudo

Orian³

2019

COC

View full text Add to dashboard Cite

Organodiselenides are an important class of compounds characterized by the presence of two adjacent covalently bonded selenium nuclei. Among them, diaryldiselenides and their parent compound diphenyl diselenide attract continuing interest in chemistry as well as in close disciplines like medicinal chemistry, pharmacology and biochemistry. A search in SCOPUS database has revealed that in the last three years 105 papers have been published on the archetypal diphenyl diselenide and its use in organic catalysis and drug tests. The reactivity of the Se-Se bond and the redox properties of selenium make diselenides efficient catalysts for numerous organic reactions, such as Bayer- Villiger oxidations of aldehydes/ketones, epoxidations of alkenes, oxidations of alcohols and nitrogen containing compounds. In addition, organodiselenides might find application as mimics of glutathione peroxidase (GPx), a family of enzymes, which, besides performing other functions, regulate the peroxide tone in the cells and control the oxidative stress level. In this review, the essential synthetic and reactivity aspects of organoselenides are collected and rationalized using the results of accurate computational studies, which have been carried out mainly in the last two decades. The results obtained in silico provide a clear explanation of the anti-oxidant activity of organodiselenides and more in general of their ability to reduce hydroperoxides. At the same time, they are useful to gain insight into some aspects of the enzymatic activity of the GPx, inspiring novel elements for rational catalyst and drug design.

show abstract

Three-Membered Rings With One Selenium or Tellurium Atom

Brydon

White

2022

Comprehensive Heterocyclic Chemistry IV

View full text Add to dashboard Cite

Synthesis of l-Selenocysteine and α-Methyl-l-Selenocysteine Derivatives Using Woollins’ Reagent and Their Application as Chiral Selenium Catalysts

Cited by 6 publications

References 45 publications

Synthesis of alpha‐methyl selenocysteine and its utilization as a glutathione peroxidase mimic

Synthesis of alpha‐methyl selenocysteine and its utilization as a glutathione peroxidase mimic

Organodiselenides: Organic Catalysis and Drug Design Learning from Glutathione Peroxidase

Three-Membered Rings With One Selenium or Tellurium Atom

Contact Info

Product

Resources

About