A practical and efficient preparation of the releasable naphthosultam side chain of a novel anti-MRSA carbapenem.
A practical large-scale synthesis of the naphthosultam-based side chain of the anti-MRSA antibiotic 1 has been achieved in 29% overall yield over seven steps from 1-methylnaphthalene. The synthesis was completed without the use of protecting groups, featuring a novel naphthosultam annelation, a chemoselective acid-catalyzed triflation, and the use of a novel naphthosultam dianion to effect functionalization through benzylic metalation.
Miller
R A
RA
Department of Process Research, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA.
Humphrey
G R
GR
Lieberman
D R
DR
Ceglia
S S
SS
Kennedy
D J
DJ
Grabowski
E J
EJ
Reider
P J
PJ
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015780:Carbapenems / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D003499:Cyclic S-Oxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D016106:Methicillin Resistance; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology
C414526:1-(2-amino-2-oxoethyl)-4-(2-(1,1-dioxido-2H-naphtho(1,8-cd)isothiazol-6-yl)ethyl)-1,4-diazoniabicyclo(2.2.2)octane; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015780:Carbapenems; D003499:Cyclic S-Oxides; D007769:Lactams; D009281:Naphthalenes