Picolyl esters

The 4-picolyl esters are prepared from N-protected annino acids by treatment with 4-(chloromethyl)pyridine/TEA (or tetramethylguanidine) in DMF (90-100 °C, 2 h) or by using DCC and pyridine-4-methanol. 

A more useful application of the electron-attracting effect of aryl subtituents is found in the cleavage of 4-picolyl derivatives of protected cysteine and tyrosine in peptide synthesis (Scheme 14).Catalytic cleavage of these derivatives is usually unattractive for SProtecting groups removable also include 3- and 4-picolyl esters. ... 

An interesting topological effect is the increased terminal chlorination of fatty acids when they are adsorbed and aligned on alumina Silicon disulfide and particularly boron sulfide have been used with advantage instead of phosphorus pentasulfide to replace carbonyl oxygen by sulfur The addition of sulfur monochloride to olefins followed by reduction of the adduct with sodium sulfide provides a convenient inexpensive route to a large number of episulfides A direct conversion of ar. nitro compounds to isothiocyanates has been reported Sec. phosphines add easily to olefins under UV-irradiation Advances in peptide synthesis include the use of acyloxyphospho-nium salts prepared with hexamethylphosphoramide a simple synthesis with triphenyl phosphite , and the use 4-picolyl esters at the... 

Application of a formaldehyde thioacetal group for protection and introduction of cystine has been demonstrated in a new synthesis of oxidized glutathione. A summary of this interesting approach has been entered in Chart 5 and additional details will be included in the pentapeptide table of a subsequent volume. Another pentapeptide synthesis published in the fall of 1972 corresponded to positions 1-5 of the fibrinogen protein C-chain. The latter substance is of interest from the standpoint of the clotting process which is complex and involves in part release of two of the three protein chains of fibrinogen by the enzyme thrombin. The fibrinogen pentapeptide synthesis was also used to further e.xplore the 4-picolyl ester (OPic) method of peptide bond formation. 

These esters are cleaved by cold alkali, by catalytic hydrogenation, by sodiiam in liquid auonmonia and by electrolytic reduction. A new procedure for the facilitation of peptide synthesis is also reported in which the carboxyl-terminal residue is incorporated as its 4-picolyl ester after each coupling reaction the product is separated by extraction into an acidic phase. 

Studies on the use of the 4-picolyl esters as soluble compounds/ and the applications of 1-aminocyclopropane-l-carboxylic acid in peptide synthesis have appeared. 

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