Amino acid synthons

The encoding tags are halophenoxy derivatives of aliphatic alcohols and are attached to either a photolabile linker as a carbonate or an oxidatively cleavable linker as an ether. The photolabile linker/tag complex is especially well suited to encode peptide libraries through attachment to approximately 1% of the amino groups of each amino acid synthon at eachstage of the synthesis. For structure determination, the tags are released by photolysis at 360 nM. 

Of similar nature are chiral halogenations using auxiliary groups. Typical examples are the conversion of esters to enantiomerically pure halohydrins (precursors to chiral epoxides) using camphor-10-sulfonic acid derivatives583 and the chiral synthesis of a-amino acid synthons via diastereoselective bromination of TV-acyl oxazolidone derivatives584. 

Optically active a-azido acids as versatile a-amino acid synthons are obtained by diaste-reoselective halogenation of chiral auxiliary-based enols or enolatest followed by stereospecific azide displacement by A(A(A, A -tetramethylguanidinium azide or alternatively... 

Amino acid synthons can be prepared from iodoalanine with no loss of optical integrity (Scheme 48). The amino acid was transformed into a novel zinc reagent through reductive metallation with a zinc-copper couple in benzene/dimethyl acetamide. This organometallic was acylated under palladium catalysis in good overall yield. ... 

The dimethyl 2-methoxycarbonyl-2-(methoxyimino)ethylphosphonate used in the Homer-Wadsworth-Emmons reaction as an amino acid synthon is prepared by masking the carbonyl group of methyl bromopymvate with methoxyamine hydrochloride before submission to a Michaelis-Arbuzov reaction with trimethyl phosphite (Scheme 8.37).5 "5 By contrast, unprotected 3-benzoyl-... 

Recently, Fmoc-N-protected (3-amino acid synthons have been prepared and used for the synthesis of (3-peptides on solid phase [103]. This methodology facilitates enormously the search for new bioactive compounds, above all through the generation of combinatorial (3-peptide libraries. In this context, (3-amino acids have been used as building blocks for RGD cyclic peptides and for the synthesis of an inhibitor of human cathepsin L, previously identified by screening and deconvolution of pentapeptide amide collections [104,105]. 

Shiori and co-workers used 5-substituted 4-oxazolecarboxylic acid esters 379 as p-hydroxy-a-amino acid synthons. They described a straightforward synthesis of 379 by acylation of an isocyanoacetic acid ester with an a-alkoxyacid 378 in the presence of diphenylphosphorylazide (DPPA) or diethylphosphoryl cyanide (DPPC) followed by base-catalyzed cyclization (Scheme 1.104). The reaction conditions do not epimerize optically active a-alkoxyacids. Dilute acid hydrolysis of 379 and reaction with (600)2 affords the protected aminotetronic acids 380. Stereoselective hydrogenation of 380 then yields the 1,4-lactones 381, key intermediates in the synthesis of amino sugars. A variety of a-alkoxyacids were studied, and some examples are shown in Table 1.30. 

IV. DEVELOPMENT OF CHIRAL NICKELACYCLES AS AMINO ACID SYNTHONS... 

Encoding and Incorporation of Rc Fmoc-Amino Acid Synthons... 

Treat the resin in each of the 31 vessels with a unique R Fmoc-amino acid synthon. For example, add a solution of Fmoc-L-alanine (50 mg, 0.16 mmol,... 

Further utility of the parent Wynberg and Staring lactone 40 was demonstrated by Tennyson and Romo. In this report, the use of trichloromethyl-(3-lactone 40 as an amino acid synthon is outlined [30]. This strategy proceeds via ring... 

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