A New Approach to the Synthesis of Piperazinomycin and Bouvardin: Facile Access to Cycloisodityrosine via an Intramolecular SNAr Reaction

A new method for the synthesis of cycloisodityrosine atropisomers I (R1 = CO2Me, R2 = NHBoc), a 14-membered m,p-cyclophane, is reported. The synthesis hinged on an efficient macrocyclization procedure for biaryl ether formation based on an intramol. SNAr reaction. The cyclization conditions are much milder and the yield is much higher than those previously reported. Moreover, the presence of the NO2 function in I provides an opportunity to introduce not only the hydroxyl group found in natural products but also others such as amino acid amide for bioactivity evaluation. 3-Fluoro-4-nitrophenylalanine II was prepd. by alkylation of a chiral bislactim ether with 3-fluoro-4-nitrobenzyl bromide; secondary amine III resulting from the double alkylation was isolated as a minor product and characterized. A mechanism was proposed for its formation. [on SciFinder (R)]


Published in:
Journal of Organic Chemistry, 61, 2, 771-4
Year:
1996
Keywords:
Note:
CAN 124:176902
34-3
Amino Acids, Peptides, and Proteins
Institut de Chimie des Substances Naturelles,Gif-sur-Yvette,Fr.
Journal
0022-3263
written in English.
173912-65-7P Role: BYP (Byproduct), PREP (Preparation) (prepn of cycloisodityrosine atropisomers via an intramol. nucleophilic arom. substitution reaction); 64755-14-2DP (Bouvardin); 83858-82-6DP (Piperazinomycin) Role: PNU (Preparation, unclassified), PREP (Preparation) (prepn of cycloisodityrosine atropisomers via an intramol. nucleophilic arom. substitution reaction); 3978-80-1; 36394-75-9; 109838-85-9; 131858-37-2 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn of cycloisodityrosine atropisomers via an intramol. nucleophilic arom. substitution reaction); 160247-84-7P; 160247-85-8P; 160247-86-9P; 173912-66-8P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn of cycloisodityrosine atropisomers via an intramol. nucleophilic arom. substitution reaction); 173912-67-9P; 174060-77-6P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn of cycloisodityrosine atropisomers via an intramol. nucleophilic arom. substitution reaction)
Laboratories:




 Record created 2010-11-25, last modified 2018-03-17


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