O to S acyl shift

SCHEME 11.6 Glycopeptide thioesterification via O-to-S acyl shift. MESNa, sodium 2-mercaptoethanesulfonate. 

H. Gaertner, Native chemical ligation through in situ O to S acyl shift, Org. Lett. 2004, 6, 4861-4864. 

A fourth method involves an intramolecular O-to-S or N-to-S acyl shift process following peptide chain assembly (Scheme 5). Typically, thiol-functionalized ester... 

As shown, under the reducing ligation conditions, 0—>S acyl transfer occurred at the o-disulfide phenolic ester as previously described (see above), to provide the thioester, which underwent transthioesteriflcation with the thiol-containing glyco-peptide (upon in situ reduction of the auxiliary disulfide bond) the transient intermediate underwent an S N acyl transfer to generate the thermodynamically favored amide bond of the doubly glycosylated peptide adduct. The auxiliary was subsequently removed through sequential methylation of the fi-ee thiol to prevent the reverse acid-mediated N S acyl shift, followed by TFA treatment. 

The splicing mechanism, which is illustrated for this intein, is shown in the accompanying equations.1 1 Step a is an N —> S or N —> O acyl shift. This is followed by transesterification (step b) which involves either thioesters (as illustrated) or oxygen esters. Formation of a succinmide intermediate (step c) releases the intein and the spliced protein. The latter must undergo an S—> N or O—> N acyl shift (step d), and the succinimide in the extein must be hydrolyzed to complete the process. 

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