Amino coupling method

Much simpler fluorine-containing nucleosides, 855 and 856, were prepared " by the coupling method. 3 -Amino-3, 5 -dideoxy-5 -fluorothymi-... 

The reaction of 5a-bromo-a-tocopherol (46) with amines was further elaborated into a procedure to use this compound as a protecting group Toe for amines and amino acids (Fig. 6.35).62 The protection effect was due to a steric blocking of the amino function by the bulky tocopheryl moiety rather than due to conversion into a non-nucleophilic amide derivative, and the Toc-protected amino acids were employed in the synthesis of dipeptides according to the dicyclohexylcarbodiimide (DCC) coupling method.64 The overall yield of the reaction sequence was reported to be largely dependent on the coupling reaction, since both installation and removal of the... 

The second approach to linear polysilanes is based on the modification of polysilanes prepared by the reductive coupling method. The severe conditions of this reaction allow only alkyl or aryl substituents at the silicon atom in the starting dichlorosilane. Therefore only alkyl or aryl substituted polysilanes are known. We have successfully prepared new polysilanes with pendant alkoxy and amino side groups. This approach allows fine tuning of the properties of... 

To accurately determine anchoring, coupling, and cleavage yields, resins are extended further with an internal reference amino acid2 (IRAA lie is used), introduced as its Fmoc derivative by standard coupling methods, at a point before introduction of the handle. 

JM Humphrey, AR Chamberlin. Chemical synthesis of natural product peptides coupling methods for the incorporation of noncoded amino acids into peptides. Chem Rev 97, 2243, 1997. 

Amino acids have been used as nucleophiles to effect the ring opening of saturated 5(477)-oxazolones 253 as a coupling method in an attempt to describe a general procedure for peptide synthesis (Scheme 7.82). However, the problems arising from racemization, that is, when a proton is present at C-4 of the oxazolone, render this procedure of limited synthetic utility. 

Amino Add Coupling Method Resin Cleavage Step Peptide Yielda (%) Ref... 

Indeed, there were those who described the azide coupling method as racemization-free. [15l However, this viewpoint proved to be overly optimistic. In 1970, Sieber reported that during a synthesis of calcitonin M by the azide method, significant epimerization occurred during two of the segment condensation steps in one of these reactions 40% of the epimerized product was observed. 16 There is a crucial detail in the experimental procedure here. The workers used tert-butyl nitrite to convert a peptide hydrazide into a peptide azide, but did not isolate the azide as was typical for research at that time. Instead, they neutralized the active intermediate in situ with DIPEA and added the amino segment for acylation. This demonstrates another important theme in the control of epimerization, the presence of a tertiary amine in the reaction mixture, even if only as a neutralization equivalent, can result in the formation of epimerized products. Indeed, most observations of racemization during... 

As a result of intense research, a wealth of protection strategies and coupling methods is available for synthesis in solution and on solid supports. Peptides of up to almost fifty amino acid residues can now be prepared in sufficient quantities for pharmacological and clinical assays, and for clinical drugs and diagnostics. Thus, in the last few years new peptide-based treatments for a series of diseases have been established. 1,2 ... 

Couplings with N-protected isoxazolidine-3-carboxylic acid can be performed without particular restrictions of the method, and the use of a mixed anhydride for acylation of amino acids or amide formation has been reported. 179 A similarly free choice of coupling methods is available for the acylation of isoxazolidine-3-carboxylic acid derivatives so far the use of carbodiimide and mixed anhydrides have been reported. 168179 Isoxazolidine-3-carboxylic acid derivatives are listed in Table 7. 

The oxazol-5(4//)-one coupling method (Scheme 4) is uniquely appropriate for C -tetra-substituted a-amino acids, since racemization or epimerization is unlikely to occur with these compounds. It represents the main methodology exploitable for fragment condensation of peptides based on C -tetrasubstituted a-amino acids. Due to the gem-dialkyl effect on the C°... 

The modification of [T-amino acids by a-selenylation and then free radical allylation leads to the formation of (A-amino acids bearing an a-allyl group (Scheme 12). Hanessian and co-workers 22 initially used this approach to produce p2 3-amino acids which were then subjected to suitable coupling procedures. Interestingly, the coupling method chosen made use of PyBOP and hence demonstrates that other peptide coupling procedures can be used in the synthesis of (3-peptides. 

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