Studies on lactams. Part XVI. Stereochemistry of β-lactam formation

Synthesis and Evaluation of Azetidinone Analogues of Combretastatin A-4 as Tubulin Targeting Agents

“…-Lactam compounds 15-17 were prepared using a modified procedure at room temperature as they were not successfully obtained by the usual conditions of the Staudinger reaction (Scheme 2, Route II). Failure to form β-lactams with 4-nitrophenylacetyl chloride under standard Staudinger conditions has previously been reported 42 . The stereochemistry of the -lactam products obtained in Staudinger reactions depends on numerous factors, including the reaction conditions, the order of addition of the reagents and the substituents present on both the imine and on the acid chloride 33,43 .…”

Synthesis, evaluation and structural studies of antiproliferative tubulin-targeting azetidin-2-ones

“…This was obtained as a yellow oil by reaction of furan-3-carbaldehyde and 4-(4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)azetidin-2-one (9) in 50.2% yield; IR (NaCl film) m max : 1740.12 cm À1 (C@O, b- 4.1.14.3. 3-(Hydroxythiophen-3-yl-methyl)-4-(4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)azetidin-2-one (33). This was obtained from thiophene-3-carbaldehyde and 4-(4-methoxyphenyl)-1-(3,4,5-trimethoxy-phenyl)azetidin-2-one (9) as a yellow powder (43.6% yield) by the above method; Mp: 69°C; IR (NaCl film) m max : 1745.08 cm À1 (C@O, b- Pyridinium chlorochromate (10 mmol) was suspended in anhydrous dichloromethane (15 mL).…”

“…b-Lactam 19 was obtained in 48% yield using milder conditions with overnight stirring at room temperature (Scheme 3, route II). 33 The b-lactam ring scaffold could also be generated directly from the appropriately substituted acetic acid and imine precursors using an acid-activating agent in a one-step reaction, without generation and isolation of the acid chloride (Scheme 3, route III). Many acid-activating agents are known in literature, for example, Mukaiyama's reagent, p-toluene-sulfonyl chloride and various phosphorous derived reagents.…”

Synthesis, biochemical and molecular modelling studies of antiproliferative azetidinones causing microtubule disruption and mitotic catastrophe

“…A modified Staudinger method (method II, Scheme 1) requiring overnight reaction was used to obtain bromo-containing β-lactam 34 as method I was unsuccessful [17]. Where the appropriate α-bromoacetate precursor was available, the Reformatsky reaction was used for azetidinone synthesis (26, Scheme 1, method III).…”