Total Synthesis of Vancomycin—Part 1: Design and Development of Methodology

✍ Scribed by K. C. Nicolaou; Hui Li; Christopher N. C. Boddy; Joshi M. Ramanjulu; Tai-Yuen Yue; Swaminathan Natarajan; Xin-Jie Chu; Stefan Bräse; Frank Rübsam

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 368 KB
• Volume: 5
• Category: Article
• ISSN: 0947-6539
• DOI: 10.1002/(sici)1521-3765(19990903)5:9<2584::aid-chem2584>3.0.co;2-b

✦ Synopsis

o-Halosubstituted aromatic triazenes (e.g. I, Scheme 1) react with aryloxides (e.g. II, Scheme 1) in the presence of CuBr ´Me 2 S, K 2 CO 3 and pyridine in acetonitrile at reflux to afford biaryl ethers (e.g. V, Scheme 1). This general methodology (Tables and) was applied to the construction of the C-O-D and D-O-E vancomycin model systems 37 (Scheme 2) and 50 (Scheme 3), demonstrating its potential in a projected total synthesis of vancomycin (1, Figure ). For the construction of the vancomycin model AB biaryl ring system, a sequential strategy involving a Suzuki coupling of the C-O-D aryl iodide 74 (Scheme 7) and boronic acid 53 (Scheme 4), followed by macrolactamization was demonstrated, in which the preformed C-O-D ring framework served to preorganize the precursor for cyclization. The latter investigation led to Suzuki-coupling-based asymmetric synthesis of biaryl systems in which 2,2bis(diphenylphosphino)-1,1'-binaphthyl (BINAP) was found to be the optimum ligand (Tables and).