Sauer katalysierter Disulfidaustausch von S‐Alkylthio‐cystein‐Derivaten

Abstract

Proton‐Catalyzed Disulfide Exchange of S‐Alkylthio Cysteine Derivatives Although N‐unprotected S‐alkylthio cysteine derivatives are relatively stable in acid solutions, N‐acylsubstituted and N‐urethane protected S‐alkylthio cysteines react easily by disulfide exchange. As a rule the frequently used tert.‐butyloxycarbonyl amino protecting group, present in ethylthio cysteine derivatives can′t be removed selectively without disulfide cleavage, whilst the 2‐(p‐biphenylyl)isopropyloxycarbonyl and the 2‐phenyl‐isopropyloxycarbonyl amino protecting groups are removable without any structure change of the alkylthio thiol protecting groups. It is advisable to realize this acid demasking of the amino groups by means of weak deblocking reagents. Comperative experiments in acid solution prove S‐tert.‐butylthio group to be the most stable protecting function, whilst isopropylthio cysteine derivatives are more stable than the corresponding S‐ethylthio compounds. All these results and experiments with addition of different thiols as well as u.v.‐spectroscopic investigations indicate, that the observed acid catalyzed disulfide exchange proceeds via a carbonyl neighbouring group effect and formation of thiazolidinium and thiazolinium intermediates, respectively.

Synthese eines geschützten cyclischen Disulfidoktapeptides A6–13 der (Ala12)‐Schafinsulin‐A‐Kette

“…Bereits friiher berichteten wir iiber Synthesen von 2 unter Verwendung des A7-Dpni-Schutzes in Kombination mit der Acm-[b] oder der Et-S-Schutzgruppe [GI an den Cysteinen in A6 und A l l . Parallel dam beschreiben wir nun ankniipfend an die Arbeiten von ZERVAS [8], HISKXY [9] und R~TTEL [lo] die Synthese des (A1al2)-Schafinsulin-A-Kettenoktapeptides 2 unter Verwendung der Kombination von Mi, 1 1-S-Trityl-iind A7-S-l)iphenylmethyl-Schutzgruppen, bei terniinale TnyqJtid Trt-Cys(Trt)-Ala-Leu-OMe ( 5 ) . Daraus wurde zunaohst der Aufbau von 9 durch eine 4 + ~-E'rag~ientverkniipfun~ angcstrebt, die durch das C-terniinale Glycin in der Carboxylkoniponente iiicht die Gefahr der Racemisicrung insich birgt (s. Schema I ) .…”