Synthesis of new 14-membered macrolide antibiotics via a novel ring contraction metathesis.
[reaction: see text] A novel ring opening ring closing metathesis (ROM-RCM) was demonstrated for cyclic conjugated dienes, effecting the excision of a C(2)H(2) unit and a net ring contraction. Applying the ring contraction metathesis, new 14-membered ring macrolide antibiotics were synthesized in a single step from existing 16-membered ring macrolides. This new class of macrolide antibiotics will provide access to new therapeutics for the treatment of macrolide-resistant bacterial infections.
Lazarova
Tsvetelina I
TI
Enanta Pharmaceuticals, 500 Arsenal Street, Watertown, Massachusetts 02472, USA. tsvetelina.lazarova@sprlus.com
Binet
Sophie M
SM
Vo
Nha H
NH
Chen
Jason S
JS
Phan
Ly T
LT
Or
Yat Sun
YS
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D004351:Drug Resistance; D004917:Erythromycin / Q000737:chemistry; D015570:Josamycin / Q000737:chemistry; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013297:Streptococcus pyogenes / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D004917:Erythromycin; D015570:Josamycin