title: A practical and efficient preparation of the releasable naphthosultam side chain of a novel anti-MRSA carbapenem.
abstract: 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.
authors.affiliation: Department of Process Research, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Miller
authors.forename: G R
authors.initials: GR
authors.lastname: Humphrey
authors.forename: D R
authors.initials: DR
authors.lastname: Lieberman
authors.forename: S S
authors.initials: SS
authors.lastname: Ceglia
authors.forename: D J
authors.initials: DJ
authors.lastname: Kennedy
authors.forename: E J
authors.initials: EJ
authors.lastname: Grabowski
authors.forename: P J
authors.initials: PJ
authors.lastname: Reider
mesh_terms: 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
chemical_list: 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