Benzyloxycarbonyl group introduction

An illustrative example of the introduction of the benzyloxycarbonyl group, and its removal by hydrogenolysis is given in the synthesis of L-prolylglycine (Expt 5.188). An alternative reagent for the removal of this protecting group is iodotrimethylsilane in acetonitrile at room temperature.229... 

Before concluding the discussion of protection of the amino group we have to mention the methods used for the preparation of N-blocked amino acid derivatives. The classical procedure, still applied for the introduction of the benzyloxycarbonyl group, is acylation with the appropriate alkyl chlorocar-bonate These, in turn, are obtained through the reaction of phosgene with the alcohol ... 

The best known group of this class is the t-butyloxycarbonyl(t-BOC) (45). Since its introduction as an amino-protecting group in peptide synthesis about seven years ago it became second in use only to the benzyloxycarbonyl group. Due to the instability of t-butylchloro-formate the /-butyloxycarbonyl derivatives are obtained by reaction of the corresponding isocyanate with t-butanoD or by the action of the amine with t-butyl-/ -nitrophenyl carbonate t-butylazido-formate , <-butylcyanoformate , t-butyl JV-hydroxysuccinimide... 

This method is used, for example, for the mild introduction of protecting groups like benzyloxycarbonyl (Z), tert-butoxycarbonyl (Boc) and p-nitrophenylethoxycarbonyl (npeoc). 

Some examples for the introduction of amino protecting groups such as 2-(4-nitro-phenyl)ethoxycarbonyl (npeoc) or benzyloxycarbonyl (Z) were already given in the compilation of carbamates produced with imidazolium caiboxylates in Section 4.6.1. 

A Paquet. Introduction of 9-fluorenylmethoxycarbonyl, trichloroethoxycarbonyl, and benzyloxycarbonyl amino protecting groups into O-unprotected hydroxyamino acids using succinimidyl carbonates. Can J Chem 60, 976, 1982. 

N-Acylation and 3-alkoxycarbonylation reactions may be achieved by conventional acylation procedures. A variety of 3-acyl derivatives 157 can be prepared most conveniently by the treatment of DPPOx 266 with carboxylic acids in the presence of a tertiary amine. tert-Butoxycarbonyl (Boc-Ox, 236) and benzyloxy carbonyl (Cbz-Ox, 267) (Cbz = benzyloxycarbonyl) compounds are of practical use for introduction of nitrogen protecting groups. ... 

The decahydroquinoline has been released from the carbohydrate auxiliary by acid-catalyzed hydrolysis. After introduction of the A-benzyloxycarbonyl (Z) group, the above-mentioned two-step reduction of the carbonyl group and the subsequent hydrogenolytic removal of the Z-group furnished enantiomerically pure 4a-epi pumiliotoxin C hydrochloride 57. 

However, most nucleophiles attack 5-oxazolones at the carbonyl group and the products are derivatives of a-amino acids formed by acyl-oxygen fission. Thus the action of alcohols, thiols, ammonia and amines leads, respectively, to esters, thioesters and amides orthophosphate anion gives acyl phosphates (Scheme 18). The use of a-amino acids in this reaction results in the establishment of a peptide link. Cysteine is acylated at the nitrogen atom in preference to the sulfur atom. Enzymes, e.g. a-chymotrypsin and papain, also readily combine with both saturated and unsaturated azlactones. A useful reagent for the introduction of an a-methylalanine residue is compound (202). Both the trifluoroacetamido and ester groups in the product are hydrolyzed by alkali to give a dipeptide. The alkaline hydrolyzate may be converted into the benzyloxycarbonyl derivative, which forms a new oxazolone on dehydration. Reaction with an ester of an amino acid then yields a protected tripeptide (equation 45). 

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