Amino acid Fmoc derivatives

Amino acid Fmoc derivative mp(°Q Fmoc derivative yield (%) Fmoc amino acid PFP ester mp(°C) Fmoc amino acid PFP ester yield (%) Ref. 

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... 

Side chain protected Fmoc amino acids, Fmoc-L-Ala-PEG-polystyrene support, BOP and HATU were obtained from PerSeptive Biosystems, Inc. DAST (diethylaminosulfur trifluoride) was obtained from Fluka Chemical Corp. and DIEA and NMM were obtained from Aldrich Chemical Co., Inc. The following Fmoc amino acid derivatives were fluorinated Ala, Phe, Gly, He, Leu, Met, Val, Asp(OfBu), Glu(OfBu), Lys(Boc), Asn(Trt), Gln(Trt), Ser(fBu) and Tyr(0/Bu), while His(Trt) and Arg(Pbf) were used as purchased. All solvents were of HPLC grade and all chemicals of Analar grade. DMF was dried over 4 Angstrom sieve before use. 

Fmoc-OSu (Su = succinimidyl), H2O, CH3CN. The advantage of Fmoc-OSu is that little or no oligopeptides are formed when amino acid derivatives are prepared. 

Fmoc derivative (Section 26.7) A fluorenylmethyloxy-carbonyl amide-protected amino acid. 

Alternatively, to avoid difficult separation of diastereomers 18a and epi-18a, the Fmoc-y9 -amino acid of unlike configuration 26 can be obtained as a single dia-stereoisomer in a three-step reaction sequence via conjugate addition of the Li-amide derived from (S)-N-benzyl-l-phenylethylamine (Davies methodology [113]) to tert-butyl tiglate [105] (Scheme 2.3). 

These amino acids were initially synthesized by asymmetric aminomethylation of optically pure (R)- and (S)-N-Acyl-4-phenyhnethyl)oxazolidin-2-ones 52 through TiCVenolates (Evans methodology [135]) with (benzoylamino)methylchloride or benzyl N-(methoxymethyl)carbamate [66, 97-99, 104]. Hydrolytic removal of the auxiliary yielded the N-protected (benzoyl or Z) amino acid 54. Deprotection afforded the free amino acid which was converted to the required Boc- or Fmoc-pro-tected derivatives (Scheme 2.7). 

Takahashi and coworkers described an effective sialylation method utilizing the N-Fmoc, N-Troc and N-trichloroacetyl-P-thiophenyl sialosides (Scheme 4.6d) [167]. It was found that the N-Troc derivative of N-acetylneuraminic acid performed better than the corresponding N-Fmoc derivative. An N-Troc P-thiosialoside was applied for the synthesis of glycosyl amino acids by one-pot glycosylation [167]. Importantly, it was found that the N-Troc protecting group could be converted into an acetamido moiety without causing racemization of the peptide. 

The allylic HYCRAM derivative was subsequently modified by insertion of a standard amino acid between the aminomethyl resin and the hydroxy butenoic acid moiety. Using this allylic anchor, the resin-linked, glycosylated HIV peptide T-derivative 164 was synthesized by application of Fmoc amino protection and sidechain protection with lert-butyl groups. The lac-tosamine peptide T (165) could be released from the resin by application of the palladium(0)-catalyzed allyl-transfer reaction to V-methyl aniline as the allyl acceptor. 

FIGURE 2.14 Peptide-bond formation from chlorides of A-alkoxycarbonylamino acids. N-9-Fluorenylmethoxycarbonylamino-acid chlorides.41 The base is NaHCO, Na2C03, or a tertiary amine. The reaction is carried out in a one- or two-phase system. The latter is used to try to suppress formation of the 2-alkoxy-5(4//)-oxazolone that is generated by the action of the base on the acid chloride. The method is applicable primarily to Fmoc-amino-acid derivatives that do not have acid-sensitive protecting groups on their side chains. 

FIGURE 8.17 Preparation of Fmoc-A-methylamino acids by methylation of Fmoc-amino acids.90 Acid-catalyzed reaction of substrate with formaldehyde at elevated temperature with removal of water by azeotropic distillation produces the oxazolidinone, which is then opened and reduced to the A-methylated derivative. 

While the distinct amino acid residues have mostly only a modulating effect (see Table 1.9) (e.g., FMOC-protected amino acids), the type of protection group or derivative formed decides on the molecular and chiral recognition mechanism and hence on the obtained elution order as well as the level of enantiomer recognition (i.e., magnitudes of a-values) that can be afforded. From a practical point of view, we may distinguish between two groups of IV-derivatives ... 

A number of nonnatural amino acids were resolved into individual enantiomers on 0-9-(2,6-diisopropylphenylcarbamoyl)quinine-based CSPby Peter and coworkers [48,90,113,114] after derivatization with Sanger s reagent, chloroformates (DNZ-Cl, FMOC-Cl, Z-Cl), Boc-anhydride, or acyl chlorides (DNB-Cl, Ac-Cl, Bz-Cl). For example, the four stereoisomers of P-methylphenylalanine, P-methyltyrosine, P-methyltryptophan, and P-methyl-l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid could be conveniently resolved as various A-derivatives [113]. The applicability spectrum of cinchonan carbamate CSPs comprises also P-amino carboxylic acid derivatives, which were, for example, investigated by Peter et al. [114]. A common trend in terms of elution order of DNP-derivatized P-amino acids was obeyed in the latter study On the utilized quinine carbamate-based CSP, the elution order was S before R for 2-aminobutyric acid, while it was R before S for the 3-amino acids having branched R substituents such as wo-butyl, iec-butyl, tert-butyl, cyclohexyl, or phenyl residues. 

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