Synthesis of Modified Carboxyl Binding Pockets of Vancomycin and Teicoplanin
Sixteen-membered macrocycle I (R = H) and 16+14 bicyclic compd. II, incorporating a terminal primary hydroxyl group in the peptide sequence, have been designed and synthesized. The syntheses feature the use of an efficient cycloetherification based on an intramol. SNAr reaction for the formation of biaryl ether bonds. Cyclization of a linear tetrapeptide, prepd. via a convergent [2+2] segment coupling, gave macrocycle I (R = Boc) (P configuration) as a single isolable atropisomer. Removal of the Boc protecting group afforded the modified carboxyl binding pocket of vancomycin (I; R = H). A sequential 2-fold intramol. SNAr reaction has been used to construct the model bicyclic system (i.e. II) of the D-O-E-F-O-G ring of teicoplanin. Cyclization conditions (CsF, DMF, room temp.) are sufficiently mild that the configuration of the racemization-prone arylglycine residue was not affected. Chiral amino acid and amino alc. building blocks were prepd. using Evans' asym. azidation method and Schollkopf's bislactim ether as a chiral glycine template. I showed interesting conformational properties compared to vancomycin and its binding with Ac-D-Ala was studied by NMR titrn. expts. A dissocn. const. (Kd = 5 * 10-4) was calcd. by a curve fitting method. II is currently the most advanced synthetic intermediate toward the total synthesis of teicoplanin. [on SciFinder (R)]
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Bois-Choussy, M., Neuville, L., Beugelmans, R., & Zhu, J. (1996). Synthesis of Modified Carboxyl Binding Pockets of Vancomycin and Teicoplanin. The Journal of Organic Chemistry, 61(26), 9309–9322. https://doi.org/10.1021/jo961412m
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1996
61
26
9309
9322
CAN 126:60327
34-3
Amino Acids, Peptides, and Proteins
Institut de Chimie des Substances Naturelles,CNRS,Gif-sur-Yvette,Fr.
Journal
written in English.
79250-46-7P; 185112-16-7P Role: BYP (Byproduct), PREP (Preparation) (prepn. of modified carboxyl binding pockets of vancomycin and teicoplanin); 621-37-4 ((3-Hydroxyphenyl)acetic acid); 15017-52-4; 36394-75-9; 78342-42-4; 89536-84-5; 90508-28-4 (N-Allyloxycarbonyl-L-alanine); 102029-44-7 ((R)-4-Benzyl-2-oxazolidinone); 163395-24-2 (3-Fluoro-4-nitrophenylacetic acid); 173775-54-7; 173775-59-2 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of modified carboxyl binding pockets of vancomycin and teicoplanin); 156945-58-3P; 156945-62-9P; 167423-69-0P; 169825-20-1P; 169825-21-2P; 169825-22-3P; 169825-25-6P; 169825-26-7P; 169825-29-0P; 173775-51-4P; 173775-52-5P; 173775-53-6P; 173775-55-8P; 173775-56-9P; 173775-57-0P; 173775-58-1P; 174759-45-6P; 185112-17-8P; 185112-18-9P; 185112-19-0P; 185112-20-3P; 185112-21-4P; 185112-24-7P; 185112-25-8P; 185112-26-9P; 185112-27-0P; 185112-28-1P; 185112-29-2P; 185112-30-5P; 185112-31-6P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of modified carboxyl binding pockets of vancomycin and teicoplanin); 169825-19-8P; 173775-49-0P; 173935-21-2P; 185112-22-5P; 185112-32-7P; 185112-33-8P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of modified carboxyl binding pockets of vancomycin and teicoplanin); 1404-90-6P (Vancomycin); 61036-62-2P (Teicoplanin) Role: PNU (Preparation, unclassified), PREP (Preparation) (synthesis of modified carboxyl binding pockets of vancomycin and teicoplanin)
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