Amino acids 9-fluorenylmethoxycarbonyl derivatives

Krausz el al. have synthesised two series of amino acid porphyrinylsugar derivatives (Fig. 5). One of them involves the coupling of adequate glycoporphyrin derivatives, prepared by pyrrole/aldehyde condensation methodology, with 9-fluorenylmethoxycarbonyl-L-alanine (Fmoc-L-alanine) to give the tri-, di-, and mono-alanine glycoporphyrin derivatives 54—57 after the deprotection step the other series (58) involves a glucosylamino acid moiety instead of the alanine in their preparation.21,44... 

Lepri et al. investigated the chromatographic behavior of racemic dinitropyridyl, dinitrophenyl, dinitrobenzoyl, 9-fluorenylmethoxycarbonyl amino acids, tryptophanamides, lactic acid derivatives, and unusual enantiomers such as binaphthols on reversed phase TLC plates developed with aqueous-organic mobile phase containing bovine serum albumin (BSA) as chiral agent. More than 75 racemates has been separated in these experiments with planar chromatography using BSA in mobile phase. BSA showed enantioselectivity towards racemates with structures completely different from amino acids, their derivatives, and similar compounds such as hydroxy acids. 

Fluorenylmethoxycarbonyl (Fmoc) derivatives of amino acids (obtained from Auspep, Australia or Merck, Germany). 

Solid-phase peptide synthesis. The combination of the base-labile N-a-fluorenylmethoxycarbonyl (Fmoc) amino acids and the acid-labile /-butyl protecting group is valuable for solid-phase peptide synthesis, particularly with polar resins. Intermediate Fmoc-peptide resins are deprotected with 20% piperidine or 5% piperazine in DMF. Six amino acid groups can be added per day without difficulty. This new strategy was used for synthesis of human /3-endorphin (31 residues), with 29 residues added as the anhydrides of Fmoc-amino acids. The last residue was the N-a-Boc derivative of 0-/-butyltyrosine. The peptide resin was cleaved with anhydrous CF3COOH. The overall yield of isolated polypeptide was 41 %. This method does not require vigorous acidic conditions. 

For a,a-dialkylamino acids enantiomerization is not a problem. The preparation of 4,4-dimethyl-2-[(9-fluorenylmethyl)oxy]-5(4F/)-oxazolone, an intermediate used in the synthesis of ( )-mirabazole C has been described. Recently, two new 2-aIkoxy-5(4F/)-oxazolones derived from Toac (2,2,6,6-tetramethyl-4-amino-l-oxy-piperidine-4-carboxylic acid) that incorporate Z or 9-fluorenylmethoxycarbonyl (Fmoc) protection at C-2 have been described. The Toac analogues were synthesized as part of a study of the crystal structure and ab initio calculations for these interesting systems. 

Amino groups are normally protected as their tm-butoxycarbonyl (Boc), carbobenzoxy-carbonyl (Z), or 9-fluorenylmethoxycarbonyl (Fmoc) derivative prepared as described in section 25.5. The Boc group may be removed by treatment with hy(kogen bromide. Other acidic reagents such as trifluoroacetic acid may also be used. 

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