Urethane type protective group

The suitability of the Aloe group for the construction of lipidated peptides is emphasized by the synthesis of the maleimidocaproyl-modified, S-palmi-toylated and farnesylated heptapeptide 16 which corresponds to the N-Ras C-terminus (Scheme 10).1211 In contrast to classical urethane-type protecting groups, the Aloe group can be removed in the presence of additional functional groups and under neutral conditions. It is therefore a very convenient protecting group for the synthesis of very hydro-phobic lipid-modified peptides, which are not soluble in the aqueous media required for enzyme catalyzed transformations. 

These reactions were effected by RuO /aq. Na(10 )/Et0Ac when the reactants bore urethane-type protecting groups (n = 1, R =Boc, R =Me, NBzl n = 2,... 

Table 1 Urethane-Type Protecting Groups Most Frequently Used for N -Protection of Amino Acids...

Acylation of anoino acids or peptides with Z-protected amino acids can be performed with aU known methods including the a-amino acid Al-carboxyanhydrides (NCAs), since protocols for the preparation of the highly reactive Z-protected NCAs are now available (see Section 3.4.2).t l Moreover, since formation of oxazol-5(4//)-ones is very slow with urethane-type protecting groups, racemization, at least by this mechanism, is largely suppressed (see Sections 1.2.1.2 and 7.4).[ 5.n,52]... 

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... 

Urethane-type Protecting Groups Derived from Primary Alcohols... 

For a-amino protection, the urethane-type protecting groups derived from secondary alcohols do not offer improved properties compared to those of more classical groups derived from primary alcohols. The main advantage possibly derived from the use of this type of urethane-derived N -derivative is the increased solubihty, e.g. such as that reported for the 2-adamantyloxycarbonyl derivatives (see Section... 

Table 1 Selected Benzyl Urethane-type Protecting Groups...

Activated derivatives of S-alkyl-cysteine suffer base catalyzed racemization even when their amino group is blocked by the benzyloxycarbonyl or other urethane-type protecting group. A simple, but not uncontested, explanation is reversible -elimination... 

Racemization during the synthesis of peptides is a complex problem. The diversity of possible courses followed in the process is compounded by the individuality of the amino acids. This was already shown on the example of S-alkyl-cysteine residues which lose chiral purity by a special mechanism even if protected by a urethane-type protecting group that prevents racemization in other acylamino acids. The opposite end of the scale is represented by proline... 

Preparation of Bpoc-protected amino acids has been shown feasible in aqueous solvents using the corresponding fluorocarbonate illustrated in Chart 1. A series of even newer urethane type-protecting groups are presented in Chart 2. In histidine chemistry, protection of the N-imidazole position with the adamantyloxycarbonyl group has been shown to offer some advantages. A... 

Merrifield s original idea was based on the general scheme of stepwise condensation of N-protected amino acids to the first one, which is linked with its carboxyl function by an ester bond to the insoluble polymer support. This way of solid phase peptide synthesis resulted from the well-known risk of racemization during activation of peptidic carboxyl components, which is minimized in activated amino acid derivatives, N-acylated by urethane-type protecting groups [40] (Fig. 7). Depending on the chosen method, the C-terminal activation of N-protected peptides tends to racemize a certain amount of the material because of the possible formation of an oxazolinone intermediate [41] (Fig. 8). 

Hydrogen-bond lengths 142 Hydrolytic cleavage, of acyl-type protecting groups 670-672, 674, 677 of urethane-type protecting groups 682... 

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