DESIGN OF NEW PHOTOACTIVATABLE AMINO-ACIDS - STEREOSELECTIVE SYNTHESIS OF N-PROTECTED PHENYLALANINE DERIVATIVES AS PRECURSORS OF P-DIAZOCYCLOHEXADIENONE-CONTAINING PEPTIDES

被引:15
作者
DUGAVE, C
机构
[1] CEA, Département d'Ingénierie et d'Etude des Proteines (DIEP), C.E. Saclay
关键词
D O I
10.1021/jo00108a023
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
4-Diazocyclohexa-2,5-dienone-based amino acids m-Dip and o-Dip were designed for building up photoactivatable peptides. Their stable precursors L-3-[3-(benzyloxy)-6-nitrophenyl]alanine (L-m-Nip(Bn)) and L-3-[2-(benzyloxy)-5-nitrophenyl]alanine (L-o-Nip(Bn)) were synthesized by stereoselective alkylation of the corresponding benzyloxynitrobenzyl iodides by a chiral glycine equivalent. Alkylation was carried out using either butyllithium in dry organic solvents or a phase transfer procedure. Alkylation, hydrolysis of the adduct, and protection as Boc and Fmoc derivatives were achieved in 57-73% overall yields and led to 97-99% optically pure material. Boc or Fmoc-m/o-Nip(Bn) was inserted in model dipeptides Ac-mlo-Nip(Bn)-Ala-OMe or tripeptides Ala-Lm-Nip-(Bn)-Lys and Ala-L-o-Nip(Bn)-Arg, respectively, by homogeneous solution procedure and by solid-phase peptide synthesis. Deprotection and diazotization of the resulting p-hydroxyanilines gave the corresponding photoactivatable 4-diazocyclohexa-2,5-dienones containing peptides in quantitative yields. Such photoprobes are stable for several hours in the dark but are rapidly photolyzed at 350 nm or at 295 nm by a tryptophan-mediated energy transfer activation process.
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页码:601 / 607
页数:7
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