Urethane-type blocking groups

Sensitivity to acids is not restricted to urethane-type blocking groups. Thus, the triphenylmethyl (trityl, Trt) group is cleaved by acetic acid and also by tetrazole in trifluoroethanol... 

The methods discussed here are applicable for the incorporation of other urethane-type blocking groups as well. In some cases the old chloride method prevails. For instance 9-fluorenylmethyl chlorocarbonate, a stable crystalline solid, allows smooth introduction of the Fmoc group. 

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... 

Cleavage of fl-halourethanes. Eckert and Ugi have found that urethanes of this type can be cleaved to the amine by treatment with the anion of 1 in acetone or methanol at room temperature. The reaction involves alkylation followed by reductive fragmentation (equation I). The rate of cleavage depends on the structure of the blocking group 2,2,2-trichloroethoxycarbonyl derivatives (R = R = C1) are cleaved within 1-5 minutes. Cobalt(II) phthalocyanine (1) is recovered in almost quantitative yield in reusable form. 

In peptide synthesis the use of a suitable protection for the N-terminal amino group is required not only to prevent the formation of a complex mixture of oligo- and cyclo-peptides, but an additional demand on the functionality applied for this purpose is that it should prevent possible racemization of the activated amino acid. Racemization usually takes place via an intermediate oxazolone (7) that forms readily from A -acyl-protected amino acids (Scheme 2). This side reaction can be mostly suppressed by using a carbamate as an N-terminal-protecting group. Therefore, nearly all blocking functions currently applied in this field are of the urethane type. 

It is not only benzyl-type urethanes which are widely used for the blocking of amino groups. This goal may also successfully be achieved by the application of alkyl urethanes. Among these, the f-butoxycar-bonyl group (t-BOC or Boc), introduced in 1957, deserves special mention. Today it probably is the most frequently used amino-protecting function in peptide synthesis. The t-BOC group can be easily... 

Non-ionic associative thickeners are usually poly(ethylene oxide) polymers whose molar mass has been extended 1 some linking group and in which hydrophobic blocks have been incorporated, usually by the same linking group. Urethane linking groups are most commonly used, and this type is now commonly called a HEUR (hydrophobe-modified ethylene oxide urethane) thickener. Because they can provide well-characterized model systems, academic research has ccxicentrated on HEUR thickoiers with tominal hydrophobes, but commercial materials may contain either or both tominal and internal hydrophobes. 

A richer behavior in dilute solution is exhibited by ABA triblock copolymers when the medium is a poor solvent for the terminal A blocks and a good solvent for the internal B block. If water is the solvent, nonionic chains of this type are obtained when poly(ethylene oxide) has been blocked at both ends with hydrophobic groups. The hydrophobic blocks can be alkyl groups [19], which might be coupled to the poly(ethylene oxide) via a urethane [20], or they can be blocks of a more hydrophobic polymer, such as poly(propylene oxide) [21,22] or poly(butylene oxide) [23,24]. Of course, ABA triblock copolymers in which all of the blocks are insoluble in water can be studied appropriately selected organic solvents [25-27]. Our recent simulations of these ABA triblock copolymers in dilute solution in a medium that is selective for the middle block are reviewed here, and comparisons are made with several recent experimental [19-27] and theoretical [28] studies. 

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