Access to Any Site‐Directed Isotopomer of Methionine, Selenomethionine, Cysteine, and Selenocysteine − Use of Simple, Efficient Modular Synthetic Reaction Schemes for Isotope Incorporation

Abstract

Simple modular reaction schemes that allow access to any isotopomer of protected serine and homoserine have been worked out. These systems could be simply converted into cysteine, selenocysteine, homocysteine, homoselenocysteine, the essential amino acid methionine, and selenomethionine by Mitsunobu chemistry. These sulfur‐ and selenium‐containing amino acids fulfil many essential roles in the living organism. In addition, homoserine could be converted in a few steps into optically active L‐vinylglycine. As well as the stable isotopes 13C, 15N, 17O, and 18O, the radioactive isotopes of sulfur, selenium and carbon can also be easily introduced in a site‐directed fashion. In view of the wide scope of the Mitsunobu reaction, we feel that many more important systems with the carbon skeleton of serine and homoserine should be preparable through this basic chemistry in any site‐directed isotopically labeled form. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Synthesis of Selenocysteine and Selenomethionine Derivatives from Sulfur‐Containing Amino Acids

“…l-SeMet (2) itself is an important synthetic target for its versatile applications to biological assays and its usefulness in derivatization to other target molecules. Lugtenburg and co-workers [38] developed efficient synthetic routes to various isotopomers of l-SeMet (2), as well as l-SeCys (1), labeled with various isotopes of 13 C, 15 N, 17 O, 77 Se, etc. Such isotopomers will be useful in the medical applications and for structure analysis of biomolecules.…”

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

“…[20][21][22] Later, more reactive bromoalanines were utilized for the synthesis of Sec derivatives. 15,[23][24][25][26] 12 the amino group of L-serine (3) was protected with Boc, and the obtained carbamate 4 was converted into methyl ester 5 (Scheme 1). The Ser derivative thus protected was tosylated to 6 and then selenated to 7 by reaction with a selenolate, which was generated from di(p-methylbenzyl) diselenide (MBnSeSeMBn) and NaBH 4 in MeOH, according to a similar procedure reported by Braga.…”

Synthesis of Selenocysteine and Its Derivatives with an Emphasis on Selenenylsulfide (SeS) Formation

“…Lugtenburg and co-workers improved the nucleophilic displacement of the serine OH group by M 2 Se 2 (Scheme 14) [38]. They activated the OH group with Ph 3 P, Br 2 , and 1H-imidazole, followed by Na 2 Se 2 prepared from the treatment of elemental selenium with NH 2 NH 2 · H 2 O and NaOH.…”