THE CHEMISTRY AND BIOLOGY OF VANCOMYCIN AND OTHER GLYCOPEPTIDE ANTIBIOTIC DERIVATIVES - Medicinal Chemistry of Bioactive Natural Products - page 35

THE CHEMISTRY AND BIOLOGY
OF VANCOMYCIN AND OTHER
GLYCOPEPTIDE ANTIBIOTIC
DERIVATIVES

R ODERICH D. S ¨ SSMUTH
Institut f ¨ r Chemie, Berlin, Germany

2.1 INTRODUCTION

Vancomycin (Scheme 2-1) is the most prominent representative of the family of
glycopeptide antibiotics. It was isolated from a culture of the gram-positive bacterial
strain Amycolatopsis orientalis in the mid 1950s in a screening program of Eli Lilly
and Company (Indianapolis, IN). 1 Since then, many structurally related glycopep-
tides have been isolated from bacterial glycopeptide producing strains. Soon after
its discovery, vancomycin served clinically as an antibiotic. However, the impurities
of byproducts caused toxic side effects that were overcome with enhanced purifica-
tion protocols. Since then, vancomycin has been used over 30 years, without the
observation of significant bacterial resistances. The first clinical-resistant isolates
were reported in the late 1980s, 2-4 and since then, this number has continuously
increased. Nowadays, vancomycin is still widely used by clinicians as an antibiotic
of last resort, especially against methicillin-resistant Staphylococcus aureus
(MRSA) strains. Because of the emergence of vancomycin-resistant strains over
the past 10 years, researchers urgently seek for alternative antibiotics to counter
the expected threat of public health. From various strategies to combat vancomycin
resistance, one is the screening and evaluation of compound classes other than
glycopeptides. However, accepting glycopeptides as validated biological lead