THE REACTION OF THIYL RADICALS WITH TRIALKYL PHOSPHITES¹

Abstract

Communications to the Editor Vol. 79 gifts3 456•7 of synthetic isomers of sphingosine made it possible to settle this point in the experiments shown in Table II in which "active ceramide'' is identified as N-acetyl-DL-threo-/TOMS-sphingosine.The possible biological significance of the fact that the enzymatically active form of sphingosine possesses the threo rather than the expected erythro configuration is currently being investigated. (6) Gift of Dr. Paul O'Connell and the Upjohn Company. (7) Gift of Prof. C. A. Grob and the Ciba Company.

Modern Extensions of Native Chemical Ligation for Chemical Protein Synthesis

“…Indeed, in the presence of TCEP, the water-soluble radical initiator 2,2 0 -azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride (VA-044) 54, and tBuSH in aqueous media, the selective desulfurization of Cys residues was readily achieved. The mechanism for this transformation presumably mirrors the one proposed by Walling et al [75,74] and involves the initial formation of a Cys thiyl radical in the presence of radical initiator 54 (Scheme 15). Addition of the sulfur-centered radical to TCEP generates a TCEP-adduct, which undergoes β-scission to produce an alanyl radical and a phosphine sulfide byproduct.…”

“…Notably, a Grx(1-38) Cys mutant, containing no Sec residues, was completely stable to the deselenization conditions [144]. Mechanistically, the phosphinemediated deselenization reaction was thought to proceed via a radical pathway (Scheme 40), similar to the one proposed for the radical desulfurization of thiols by trialkylphosphites and trialkylphosphines [74,75] and implicated by Danishefsky and coworkers in their development of the metal-free radical desulfurization protocol [72]. Although proceeding through similar pathways, the observed selectivity of the deselenization reaction for Sec over Cys might be attributed to the preferential formation of selenium-centered radicals over the corresponding sulfur-centered radicals, particularly under the mild conditions employed for deselenization.…”

Free‐Radical‐Based, Specific Desulfurization of Cysteine: A Powerful Advance in the Synthesis of Polypeptides and Glycopolypeptides

“…[14] Soon thereafter, in a key advance, Walling and Rabinowitz put forth a proposed mechanistic sequence, wherein an alkylthiyl radical adds reversibly to phosphite, thereby generating an intermediate phosphoranyl radical. [15] Subsequent b scission was envisioned to provide an alkyl radical, and rapid hydrogen abstraction from the parent thiol would furnish the product alkane, thereby serving to propogate the chain (Scheme 1). In addition to this contribution to the mechanistic understanding of the reduction, Walling et al extended the reaction to trialkylphosphines.…”

Native chemische Verknüpfung mit Valin

“…[10] bei der ein wässerlöslicher Radikalstarter ein Wasserstoffatom der Cystein-Thiolfunktion abstrahiert und die anschließende Reduktion durch TCEP ein Alanylradikal liefert. [11] Dieses Alkylradikal empfängt ein Wasserstoffatom von einer Thiolgruppe eines nicht umgesetzten Cystein-Peptids oder von EtSH oder tBuSH, die zur Beschleunigung der Produktbildung zugesetzt werden. Unter den beschriebenen Bedingungen (VA-044, TCEP, EtSH und tBuSH) gelang die Entschwefelung des Penicillamin-Peptids 11 zu 17.…”

“…Die Verfüg-barkeit geeignet geschützter Penicillamin-Synthesebausteine Abbildung 2. Metallfreie Entschwefelung des Penicillamin enthaltenden Peptids Leu-Tyr-Lys-Ala-Gly-Pen-Arg-Ala-Glu-Tyr-Ser-NH 2 (11 …”