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Total Synthesis of Vancomycin—Part 2: Retrosynthetic Analysis, Synthesis of Amino Acid Building Blocks and Strategy Evaluations
Author(s) -
Nicolaou K. C.,
Boddy Christopher N. C.,
Li Hui,
Koumbis Alexandros E.,
Hughes Robert,
Natarajan Swaminathan,
Jain Nareshkumar F.,
Ramanjulu Joshi M.,
Bräse Stefan,
Solomon Michael E.
Publication year - 1999
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/(sici)1521-3765(19990903)5:9<2602::aid-chem2602>3.0.co;2-x
Subject(s) - glycopeptide , vancomycin , glycopeptide antibiotic , retrosynthetic analysis , chemistry , combinatorial chemistry , derivative (finance) , williamson ether synthesis , total synthesis , stereochemistry , amino acid , stereoselectivity , ether , organic chemistry , antibiotics , catalysis , biochemistry , biology , bacteria , financial economics , economics , genetics , staphylococcus aureus
A number of valuable new synthetic strategies , such as the triazene‐driven biaryl ether synthesis, have been developed during the total synthesis of vancomycin ( 1 ). Modern catalytic asymmetric reactions were employed for the construction of the required amino acid building blocks, which were then assembled to the appropriate peptide fragments, whose cyclization in the order C‐O‐D→AB/C‐O‐D→AB/C‐O‐D‐E led to framework of the vancomycin aglycon ( 2 ). Sequential attachment of the required sugar moieties onto a suitably protected aglycon derivative, followed by deprotection, allowed the stereoselective total synthesis of the glycopeptide antibiotic vancomycin ( 1 ).