Acylation hydroxy groups with acidic function

A simple approach for lipidation of peptides with di-fatty acid substituted glycerol moieties is based on the use of glyceric acid.119" For this purpose (2i )-glyceric acid is esterified at the two hydroxy groups with fatty acid acyl chlorides and the resulting lipophilic synthon (18) is used directly as an active ester, e.g. Pfp ester, to acylate selected amino groups of peptides, or is used to acylate suitably functionalized spacers. 

When acylations of nucleosides with acid anhydrides in the presence of lipase from Pseudomonas fluorescence (PFL) in DMF or DMSO as the solvent first proceeded, the regioselectivity was unsatisfactory 1252l However, this lipase together with subtilisin can be utilized to effect highly specific deacylations of various pyrimidine nucleosides 145 (Fig. 18-18) 1253l Thus, lipase from Pseudomonas fluorescence (PFL) preferably attacks the hexanoyl group on the secondary hydroxy function of the N-... 

Acetic anhydride has also been used as the acylating agent. The formation of thiiranes from thiocyanatohydrins having a tertiary hydroxy group is best achieved by p-toluenesulfonic acid-catalyzed acetylation.The analogous thiocyanatohydrins with a secondary hydroxyl and a tertiary thiocyanate function give a predominance of epoxide from thiocyanatohydrin acetates since the hydrolysis rate of the secondary acetate grouping becomes competitive with that of the tertiary thiocyanate. 

Under the conditions used in peptide synthesis, unprotected aliphatic hydroxy groups can undergo two types of side reactions they can be acylated or dehydrated, the latter leading to dehydroamino acids. The hydroxy group of serine is a primary alcoholic function and therefore exhibits the highest reactivity. The secondary alcoholic functions of threonine, hydroxyproline, (3-phenylserine, hydroxynorvaline, and hydroxynorleucine, as well as of other noncoded amino acids, are less reactive and thus more suited for use in the unprotected form. The aromatic hydroxy group of tyrosine is more acidic than the ahphatic hydroxy groups nevertheless, it can be acylated to form esters. These are active esters which in turn can react with primary amines to form amide bonds. 

Hydroxy protection, the temporary protection of the primary and secondary hydroxy functions of Ser and Thr, respectively, and the aromatic hydroxy group of Tyr in peptide synthesis. The blocking of these functionalities is necessary as they can react with acylating reagents. In SPPS, these amino acids are usually protected as benzyl ethers applying Boc/Bzl tactics or as tert.-butyl ethers in Fmoc/Bu chemistry. 

The intramolecular cyclization of ureas derived from 3-hydroxy-4-pentenylamines and 4-hydroxy-5-hexenylamines was also investigated (Table 5)3 From these (chiral) substrates two different products can arise because the intermediate Pd-acyl species can either react with the hydroxy group to form a lactone or with the nitrogen function to form a cyclic urea derivative. The selectivity was found to depend both on the substrate and on the acidity of the solvent (MeOH or AcOH). 

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