Adoc protective group

The reagents for the synthesis of Al -l-adamantyloxycarbonyl amino acid derivatives are similar to those used for other urethane-type protecting groups (Scheme 36). Although the related 1-adamantyl chloroformate (Adoc-Cl, 68) is obtained as crystalline solid, the acylation of amino acids under Schotten-Baumann conditions leads to significant decomposition of the reagent and thus its use does not result in satisfactory yields in all cases. Better results are obtained with 1-adamantyl fluoroformate (Adoc-F, 69) (yields of A -Adoc amino acids 85-95%)P I which is conunerciaUy available or readily prepared from adamantan-l-ol and... 

Cleavage of Al-Adoc derivatives is performed concurrently with the cleavage of ferf-butyl alcohol derived protecting groups, i.e. under the relatively nuld TFA conditions in the presence of suitable scavengers (see Section 2.1.1.1.3.1.3). 

A further urethane protecting group derived from a secondary alcohol is the 2-ada-mantyloxycarbonyl group.It is more stable toward acidic reaction conditions than the corresponding 1-adamantyloxycarbonyl group (1-Adoc, Section 2.1.2.2.3.3.2), but it is removed with trifluoromethanesulfonic acid or anhydrous HF in a few minutes at... 

For chain-elongation steps with Fmoc-Arg(Adoc)2-OH standard activation procedures are applied, such as active esters and the symmetric anhydride method, but even for the use of more powerful acylating agents, e.g. phosphonium and uronium salts, there are no contraindications. Final deprotection is performed using TFA under standard conditions of Fmoc/tBu chemistry. Properties similar to the Adoc group have been reported for iso-bornyloxycarbonyl protection, whereas increased acid lability is obtained with the 1-(1-adamantyl)- -methylethoxycarbonyl group. ... 

However, in the cases examined so far, the molar solubility in DMF has not increased significantly. The 1-adamantyloxycarbonyl (1-Adoc) group could potentially improve the solubility of amino acids and peptides protected by 1-Adoc in organic solvents due to its strong hydrophobicity.P Lys(l-Adoc) was successfully employed in the synthesis of peptide histidine isoleucine (PHI) (Scheme 9)P9 and in the synthesis of a peptide fragment of a lysozyme.P l... 

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