1- (1-adamantyl) -1-methylethoxycarbonyl group

The structure of the ADPOC protecting group

1- (1-Adamantyl) -1-methylethoxycarbonyl ( ADPOC ) serves as a protective group for amines , for example in peptide synthesis . Compared to similar protective groups, their advantage is that they are stable to hydrogenolysis and can be split off even under very mild acidic conditions. This is of particular interest in the case of peptide syntheses, since excessively acidic conditions can lead to the decomposition of the peptide .

synthesis

The ADPOC protecting group can be prepared in several synthesis steps starting from adamantane-1-carboxylic acid . In the first step, the carboxylic acid chloride is first formed with phosphorus (V) chloride, which is reacted with ethyl ester corresponding to ethanol . In the second step, the ester is converted into an alcohol with two equivalents of the Grignard reagent formed from methyl iodide , which is then converted into a second ester with phenyl chloroacetate . This ester can now be used to protect an amine.

Synthesis of an ADPOC protected amine. Ad = 1-adamantyl, Ph = phenyl .

Disadvantages of this synthetic route are the by-product phenol , which has to be removed from the product over several crystallization steps, as well as the low yields and the reaction conditions (50 ° C.), which can lead to the decomposition of the peptide used. Another synthetic route that circumvents this problem is based on the production of a fluorine derivative of ADPOC. For this purpose, the alcohol is reacted with fluoroformic acid chloride, whereby the ADPOC fluoride is formed. This can be used for protection even at significantly lower temperatures (−40 ° C) and also delivers better yields.

literature

Wolfgang Voelter, Hubert Kalbacher: Investigations with selective cleavage reagents for ADPOC-protected amino acids and peptides . In: Liebigs Annalen der Chemie 2 (1993), pp. 131-136; doi : 10.1002 / jlac.199319930124 .
Sarina Krauss: New ways of presenting hypothalamus regulation hormones and enkephalins . Dissertation, 2000; urn : nbn: de: bsz: 21-opus-1703 .

Individual evidence

↑ ^a ^b H. Kalbacher, W. Voelter: 1- (1-Adamantyl) -1-methylethoxycarbonyl: A new protective group for peptide syntheses , in: Angew. Chem. 1978 , 90 , 998-999; doi : 10.1002 / anie.19780901219 .
↑ H. Kalbacher, W. Voelter: 1 - (1-Adamanty1) -1 -methylethoxycarbonyl (Adpoc) Fluoride, a Useful Reagent for Synthesis of a New Class of Protected Amino-acids with Advantageous Properties for Peptide Synthesis , in: J. Chem. Soc. Chem. Comm. 1980 , 1265-1266; doi : 10.1039 / C39800001265 .

[kalb-1] H. Kalbacher, W. Voelter: 1- (1-Adamantyl) -1-methylethoxycarbonyl: A new protective group for peptide syntheses , in: Angew. Chem. 1978 , 90 , 998-999; doi : 10.1002 / anie.19780901219 .

[2] H. Kalbacher, W. Voelter: 1 - (1-Adamanty1) -1 -methylethoxycarbonyl (Adpoc) Fluoride, a Useful Reagent for Synthesis of a New Class of Protected Amino-acids with Advantageous Properties for Peptide Synthesis , in: J. Chem. Soc. Chem. Comm. 1980 , 1265-1266; doi : 10.1039 / C39800001265 .