Carbapenem and penem antibiotics. V. Carbapenem and penem antibiotics. VI. Synthesis and antibacterial activity of 2-heteroaromatic-thiomethyl and 2-carbamoyloxymethyl 1-methylcarbapenems.

Novel Synthesis of Carbapenam by Intramolecular Attack of Lactam Nitrogen toward η1-Allenyl and η3-Propargylpalladium Complex

“…It is known that a carbapenam skeleton having a 1β-methyl group is both metabolically and chemically more stable than a nonsubstituented carbapenem skeleton, and attention has therefore been recently focused on its unique biological properties. A mixture of two diastereomers 13 (ratio of 1 to 1) was ozonolyzed to aldehyde 14 , and this was followed by reaction with lithium acetylide to give propargyl alcohol 15 . Three isomers were separated by column chromatography on silica gel, and isomer 15 - 1 β having a β-methyl group was silylated to give 16 .…”

Synthesis of 3-Alkoxycarbonyl-1β-methylcarbapenem by Using the Palladium-Catalyzed C−N Bond-Forming Reaction between Vinyl Halide and β-Lactam Nitrogen

“…At first, we investigated the reaction of amide nitrogen in the β-lactam ring with vinyl bromide having a silyloxymethyl group in palladium-catalyzed amidation. Vinyl bromide 6 was synthesized from 2-azetidinone 1 (Scheme ) to give Z -vinyl bromide 4 in 78% yield along with E -vinyl bromide in 13% yield.…”

Synthesis of 2-(Hydroxymethyl)-1β-methylcarbapenem. Chemoselective Organometallic Addition to 3-Substituted 4-[(R)-1-Carboxyethyl]azetidin-2-one

“…To date, only a limited number of methodologies for the synthesis of 2-(hydroxymethyl)-1β-methylcarbapenems have been published. − One representative method, developed at Merck, , involved the introduction of the hydroxy group α to the methyl ketone by oxidation of a lithium enolate using MoOPH reagent followed by Wittig cyclization (Scheme ). Another method, reported by a Shionogi group, described the construction of the hydroxymethyl ketone functionality from an azetidinone epoxide derivative,9a or preferably from a protected allylic alcohol by ozonolysis 9b. Unfortunately, none of these methods was suitable to meet our needs for large-scale synthesis due either to low chemical yield and poor reproducibility or to tedious separation of two diastereomers and lengthy synthetic sequences.…”