Total Synthesis of Vancomycin Aglycon-Part 1: Synthesis of Amino Acids 4-7 and Construction of the AB-COD Ring Skeleton

K C Nicolaou; Swaminathan Natarajan; Hui Li; Nareshkumar F Jain; Robert Hughes; Michael E Solomon; Joshi M Ramanjulu; Christopher N C Boddy; Masaru Takayanagi

doi:10.1002/(SICI)1521-3773(19981016)37:19<2708::AID-ANIE2708>3.0.CO;2-E

Total Synthesis of Vancomycin Aglycon-Part 1: Synthesis of Amino Acids 4-7 and Construction of the AB-COD Ring Skeleton

Angew Chem Int Ed Engl. 1998 Oct 16;37(19):2708-2714. doi: 10.1002/(SICI)1521-3773(19981016)37:19<2708::AID-ANIE2708>3.0.CO;2-E.

Authors

K C Nicolaou¹, Swaminathan Natarajan¹, Hui Li¹, Nareshkumar F Jain¹, Robert Hughes¹, Michael E Solomon¹, Joshi M Ramanjulu¹, Christopher N C Boddy¹, Masaru Takayanagi¹

Affiliation

¹ Department of Chemistry and, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037 (USA), Fax: (+1) 619-784-2469 (and) Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093 (USA).

Abstract

A triazene-based synthetic strategy for the construction of the complex biaryl ethers and a Suzuki coupling reaction were the key steps in the synthesis of precursor 1 of the aglycon of vancomycin, which already contains the complete skeleton of the target compound. The cleavage of the triazene unit from the D ring and the removal of the other protecting groups led to the aglycon of vancomycin. These strategies should be particularly valuable for the synthesis of other naturally occurring glycopeptide antibiotics and offer opportunities for the synthesis of combinatorial libraries of compounds of the vancomycin family for chemical biology studies.

Keywords: Amino acids; Antibiotics; Natural products; Synthetic methods; Vancomycin.