Aminoacids fluorination

The preparation of fluorinated catechols and phenols and particularly fluori-nated derivatives of the catecholamines and aminoacids has led to the search for methods which do not induce racemization of chiral precursors. Benzaldehydes and alkoxybenzaldehydes are considered as latent phenols and catechols respec-... 

The changing perspective on the viability of fluorine as a reagent is illustrated by the fact that many selective fluorinations of substrates [8] containing carbon centres of high electron density have now been described, including a variety of enolate derivatives [71, 72], stabilised carbanions [73, 74], steroids [75] and 1,3-dicarbonyl derivatives [76] (Table 3.2) as well as some aromatic compounds [77]. Fluorinated aminoacids have been obtained by direct fluorination [78] (Figure 3.10). 

Fluorination of Aminoacids and Amines. Fluorinated analogs of naturally occurring aminoacids and amines exhibit unique physiological activities. A number of fluorine containing amino acids have been synthesized and studied as potential enzyme inhibitors and therapeutic agents... 

Relaxation-related work on proteins and polypeptides makes typically use of H, and NMR. A couple of papers have dealt with measurements on in fluorine-labelled aminoacids incorporated into peptide stuctures. Shi and co-workers introduced, at some specific sites, an unnatural fluorine-containing aminoacid and a nitroxide spin-label into a multidomain protein known to exist in different conformations. Measurements of F PRE allowed to determine the conformation under different conditions. Suzuki et used another fluorine-containing amino acid, inserted into different parts of a membrane-active peptide, as a local dynamics probe. They measured F transverse relaxation to examine changes in the mobility in different regions of the peptide upon binding to a lipid bilayer. 

Among the numerous approaches described to graft a perfluoroalkyl chain on an aminoacid skeleton, the methods allowing one to create a C-C bond between the fluorinated part and the amino acid are of special interest. The access to this less frequently encountered type of compound uses classical methods of synthesis, such as that leading to the perfluoroalkyl-glycine 31 (Scheme 27). The compounds 31 are barely soluble, except for the betaine derivatives 32, which are obtained with very poor yields, however [64], The perfluoroalkyl-glycines have been condensed on cholic acid (Scheme 28) to give products 33, also with unsatisfactory yields [37]. 

---