188446-28-8Relevant academic research and scientific papers
Total synthesis of vancomycin - Part 2: Retrosynthetic analysis, synthesis of amino acid building blocks and strategy evaluations
Nicolaou,Boddy, Christopher N. C.,Li, Hui,Koumbis, Alexandros E.,Hughes, Robert,Natarajan, Swaminathan,Jain, Nareshkumar F.,Ramanjulu, Joshi M.,Braese, Stefan,Solomon, Michael E.
, p. 2602 - 2621 (2007/10/03)
Retrosynthetic analysis of vancomycin (1) defined vancomycin's aglycon (2) and protected triazene 3 (Figure 1) as advanced intermediates for an eventual total synthesis. Sequential assembly of 3 as shown in Figure 2 (strategy I) and Figure 3 (strategy II) led to amino acid building blocks 8-10 and 12-15, respectively, representing vancomycin's amino acids AA-1 to AA-7. These amino acid fragments were constructed by stereoselective routes and the two synthetic strategies were tested for feasibility. Strategy I, postulating construction of the vancomycin main framework in the order of D-O-E→D-O-E/C-O-D→D-O-E/C-O-D/A-B, suffered from serious epimerization problems at the AA-4 stereocenter; while strategy II, involving the sequence C-O-D→C-O-D/AB→C-O-D/AB/D-O-E proved viable. These findings set the stage for the final drive towards vancomycin's aglycon (2) and vancomycin (1).
Synthesis of (9R,12S)- and (9S,12S)-cycloisodityrosine and their N-methyl derivatives
Boger, Dale L.,Zhou, Jiacheng,Borzilleri, Robert M.,Nukui, Seiji,Castle, Steven L.
, p. 2054 - 2069 (2007/10/03)
Full details of the synthesis of (9R,12S)- and (9S,12S)-cycloisodityrosine and their N-methyl derivatives are detailed based on an intramolecular nucleophilic aromatic substitution reaction for formation of the key biaryl ether with 14-membered ring macrocyclization. Their comparison with prior samples and the documentation of a facile C9 epimerization within the natural 9S series are described.
