Das Verhalten einiger S‐Acyl‐aminomercaptane

Abstract

Das von F. L y n e n in der Natur aufgefundene Prinzip der energiereich gebundenen ,,aktivierten" Essigsaurel), die sich als S-Acetylderivat des Coenzyms A erwiesen hat, konnte in unserem Laboratorium erfolgreich auf Carbobenzoxy-aminosaurenz) und Aminosauren3) iibertragen werden, die sich durch Bindung an Thiophenol in energiereiche Ausgangsstoffe fur Amid-und Peptid-Synthesen uberfuhren lieBen. Im Bestreben zellverwandtere Modellsubstanzen fur eine vermutete Beteiligung einer Sulfhydrylverbindung bei der biologischen Peptid-Synthese zu gewinnen, haben wir nun versucht, S-Amino-acyl-Verbindungen des als Baustein des Coenzyms A erkannten Cysteamins (Thioaethanolamin, I) und seines N-Dimethylderivats (11) darzustellen, um ihre Stabilitat in waBriger Losung kennenzulernen. Wir haben zu diesem Zweck die S-Acylierungsmethode mit Saurechloriden angewendet und sie, bevor wir Aminosiiurechloride zum Umsatz brachten, am Cysteamin zunachst mit Acetylchlorid ausprobiert. H:N-CH:-CH,-SH (I) (CH,),N-CH,--CH:-SH (11)S -A c y l v e r b i n d u n g e n d e s C y s t e a m i n s (I) Zu deren Synthese sollte die Aminogruppe nicht substituiert werden, sie muBte aber trotzdem vor dem A n g r 8 durch das Saurechlorid geschutzt sein. Diese Aufgabe war recht einfach zu losen, da sich zeigte, daB das trockene Hydrochlorid von I beim kurzen Emarmen mit iiberschussigem Acetylchlorid unter kraftiger HCI-Entwicklung nahezu quantitativ in das gewunschte S-Acetylcysteamin-hydrochlorid (111) uberging. Die Verwendung von Essigsgureanhydrid liefert I11 nur in geringer Ausbeute, wahrend die Hauptmenge in eine in Alkohol leicht losliche Substanz ubergeht. Wir vermuten, da13 sich dabei ein Salz des schon von Gabriel*) beschriebenen 2-Methylthiazolins (VI) bildet, dessen Hydrochlorid wir nach der Einwirkung von Acetylchlorid auf N-Acetyl-cysteamin 1) F.

Studies on the acylation of 4-(2-aminoethylthio)-7-nitrobenzofurazan: the role of bases in promoting the formation of fluorescent S-acyl derivatives through S–N Smiles rearrangement

“…Cysteamine-NDBf 2 was prepared in almost quantitative yield through the reaction of cysteamine hydrochloride (1.1 eq) with NDBf-Cl 1 (1.0 eq) in refluxing ethanol and in the presence of a catalytic amount of KOAc (Scheme 1). [10][11][12][13][14][15][16][17][18] As expected the more nucleophilic sulfur of cysteamine reacts with NDBf-Cl 1 faster than nitrogen atom leading selectively to C4-S derivative 2 while no traces of the C4-N regioisomer were observed. We first decided to react 2 with different bases under mild conditions (DCM, 25 °C), in order to investigate its tendency to give the S-N-Smile rearrangement (Scheme 2, Table 1).…”

“…A base mediated equilibration between N-and S-acyl derivates 3a and 4a was then hypothesized and, in order to explain these results, we decided to treat compound 4a with 2 eq of Et 3 N. Quantitative conversion of 4a into 3a was observed by 1 H-NMR within 24h proving that compound 4a is the kinetic product of the reaction and compound 3a is the thermodynamic. According to Wieland and Bokelmann studies on cysteamine, 17 a plausible mechanism for the conversion of 4a into 3a is reported in Scheme 3. On the basis of this result we can assume that the treatment of 2 with Et 3 N led to 5 and addition of the ThCl after 2h led to the formation of kinetic product 4a.…”

Intramolecular Reversible Addition Reactions to the C=O Group

“…For this reason an acetyl group migrates more rapidly than a benzoyl group. Thus, for example, the rate of S-acetylmercaptoethylamine transformation into the corresponding thiol is higher by an order of magnitude than that of the rearrangement of S-benzoylmercaptoethylamine [635]. The acceleration of the migration of a trichloroacetyl group is even greater.…”

Studies on the disproportionation of mixed anhydrides of N‐alkoxycarbonylamino acids

“…The MxAn method of coupling involves addition of an alkyl chloroformate (R'OCOCI) to an acid (RCOOH) in the presence of a tertiary amine to give the MxAn (RCO-0-COOR3), which is then reacted without isolation with the amino group of a second component (1)(2)(3)(4)(5). MxAn's of acylamino or peptide acids readily undergo cyclization to the 2-alkyl-5(4H)-oxazolone (6); this is the source of partial racemization that often occurs at the activated residue (5).…”

“…Reaction of the latter with the activated species generates ester (7). AlkOx's were not known at the time of the original studies (1 -3), and ever since their development it has been suggested, without any study of the pure compounds, that MxAn's undergo decomposition via two pathways, one giving the ester and CO., the other giving the SyAn 6 and the dialkylpyrocarbonate 4 (3,5). A detailed study of MxAn's of acids not bearing a substituted amino group (RCO-0-COOR') demonstrated that both pathways indeed occur, disproportionation to the symmetrical anhydride (RC0)zO and dialkylpyrocarbonate ( R 3 0 C 0 ) 2 0 occurring at temperatures > 150°C (9, 10).…”