Aminoacids unnatural

In the synthesis of peptides such as bradykinin the use of the configurationally correct aminoacid is obligatory and semi-synthesis and total synthesis here become indistinguishable. By contrast the unnatural dipeptide sweetening agent, aspartame (ref. 106) illustrates the scope for semi-synthesis. 

Unnatural N-aryl dipeptides can be easily obtained using our procedure direct acylation of a-aminoacid esters with nitro-benzoyl chlorides followed by reductive alkylation leads to the preparation of derivatives of methyl prolinate 1 and methyl valinate 2 (Table 3). A small but significant diastereoisomeric excess (d.e.) of 20-30% is measured by NMR. Optimisation of the reaction conditions as well as of the nature of the inductor may generate better d.e.. These... 

A new application of the Schmidt rearrangement is to give unnatural aminoacids <91BMC125>. Treatment of the optically active cyclic -ketoester (266) with hydrazoic acid gives the optically active azepinone (267) which upon selective reduction with diborane furnishes the novel cyclic amino acid ester (268) (Scheme 36). 

Discovered in the middle of the 19th century, the Strecker reaction is one of the earliest atom-economic multicomponent reactions. Amino nitriles were simply obtained from ammonia, hydrogen cyanide and an aldehyde. These products are important intermediates for the synthesis of natural and unnatural a-aminoacids. Due to the ever-increased demand for enantioenri-chied a-aminoacids, the asymmetric Strecker reaction has emerged as a viable synthetic method. Since the first report published in 1996, the catalytic enantioselective cyanation of preformed imines was intensively studied and several excellent reviews were devoted to this topic. ... 

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. 

We have also studied complexation of more complex derivatives natural (of the L-series) and unnatural (D-) aminoacids. The association constants (in chloroform-methanol-4 1) were high [ca. 10 M ) but (except of alanine) enantioselectivity was negligible. In DMSO the Kg values were lower by two orders of magnitude but enantioselectivity was very similar again the highest (Kd/Kl) value was noted for alanine. The results are shown in Table 1. 

The commercial BOP reagent ((Benzotriazolylo)y)tris(dimethyIamino]-phosphonium hexafluorophosphate) was used as a coupling reagent for the synthesis of unnatural aminoacids (Scheme 10). Heras et al. described the incorporation of a range of nucleophiles including amino ester residues at position 4 of an electron-rich 2-amino-4(3H)-pyrimidinone. ... 

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