Protective groups thioesters

The synthesis of lipidated peptides is implicated by the base-lability of the thioester and the acid sensitivity of the prenyl group double bonds. Thus, new protecting groups are required which can be removed under extremely mild, preferably neutral, conditions. 

Partially protected peptide thioesters that are prepared from SPPS and purified by RP-HPLC can condense with other peptide segments to form highly homologous peptides which can comprise as many as 100 amino acid residues. 9 Syntheses of peptide thioesters using Boc-SPPS have been quite successful.161214 However, the preparation of thioesters by Fmoc chemistry is difficult because the piperidine used to remove the Fmoc group attacks the carbonyl moiety of the resin-bound thioester to release the peptide from solid support. However, peptide thioesters have been prepared by SPPS using Fmoc chemistry. 9 ... 

The construction of the maleic anhydride moiety 44 in only five steps starts with the conversion of the amide into an appropriate thioester. Upon treatment with DBU, an aldol-type cyclization occurs to provide the /1-hydroxy thiolactone as a single diastereomer. After removal of the allylic protecting group, dehydration and decarboxylation are carried out simultaneously by simple heating. The thiobutenolide is oxidized to the corresponding thio-... 

The utility of thiol esters and carbonates as protecting groups is limited by their vulnerability to hydrolysis, The poor overlap between the non-bonded electrons on the sulfur atom (3p) and the n-system of the carbonyl (2p) precludes or diminishes resonance stabilisation of the type enjoyed by normal esters thereby raising their ground state energy, The carbonyl group of the thioester is more electrophilic than a normal ester and hence more reactive. Thiocarbonate derivatives are marginally more stable. The 5-benzoyl derivative of cysteine is 95% hydrolysed in 30 minutes with 2 M ammonia whereas the 5-benzyloxycarbonyl derivative is only 20% hydrolysed in 30 minutes under the same conditions.54... 

Key Words Acidolytic cleavage backbone amide linkage bioconjugate chemical ligation combinatorial chemistry handle linker peptide alcohol peptide aldehyde peptide ester peptide thioester protecting group solid support. 

Denis B, Trifilieff E. Synthesis of palmitoyl-thioester T-cell epitopes of myelin proteohpid protein (PLP). Comparison of two thiol protecting groups (StBu and Mmt) for on-resin acylation. J. Pept. Sci. 2000 6 372-377. 

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