A Simple Preparation of 3-Benzylidene-2-azetidinones

Ru-catalyzed cross-metathesis (CM) reaction between β-arylated α-methylidene-β-lactams and terminal olefins was developed. The CM reaction is effectively catalyzed with Hoveyda-Grubbs second-generation catalyst affording corresponding α-alkylidene-β-aryl-β-lactams in good isolated yields (41-83%) with exclusive Z-selectivity. The developed protocol was successfully applied for stereoselective preparation of Ezetimibe, the commercial cholesterol absorption inhibitor.

show abstract

“…Column chromatography furnished 23 mg (66%) of the title compound as yellow needles. NMR data were in agreement with the reported values …”

Section: Methodssupporting

confidence: 92%

“…NMR data were in agreement with the reported values. 28 (Z)-1,4-Diphenyl-3-(4-cyanobenzylidene)azetidin-2-one (3ac). Following the general procedure (method B), the reaction was carried out with 1a (23 mg, 0.10 mmol) and 2c (0.026 mL, 0.20 mmol).…”

Section: Scheme 3 Synthesis Of (3r4s7s)-5 From (Ss)-3bomentioning

confidence: 99%

Stereoselective Synthesis of Ezetimibe via Cross-Metathesis of Homoallylalcohols and α-Methylidene-β-Lactams

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Subsequent to our initial biochemical evaluation of the 3-vinyl-β-lactam CA-4 analogues, a further series of 3-substituted β-lactams was prepared from 3-unsubstituted β-lactams by aldol type reaction with a suitable electrophile [54,55]. We were particularly interested in the introduction of modified alkene substituents at C-3, due to the exceptional biochemical activity displayed by the 3-vinyl β-lactam 7s .…”

Section: Resultsmentioning

confidence: 99%

3-Vinylazetidin-2-Ones: Synthesis, Antiproliferative and Tubulin Destabilizing Activity in MCF-7 and MDA-MB-231 Breast Cancer Cells

et al. 2019

View full text Add to dashboard Cite

Microtubule-targeted drugs are essential chemotherapeutic agents for various types of cancer. A series of 3-vinyl-β-lactams (2-azetidinones) were designed, synthesized and evaluated as potential tubulin polymerization inhibitors, and for their antiproliferative effects in breast cancer cells. These compounds showed potent activity in MCF-7 breast cancer cells with an IC50 value of 8 nM for compound 7s 4-[3-Hydroxy-4-methoxyphenyl]-1-(3,4,5-trimethoxyphenyl)-3-vinylazetidin-2-one) which was comparable to the activity of Combretastatin A-4. Compound 7s had minimal cytotoxicity against both non-tumorigenic HEK-293T cells and murine mammary epithelial cells. The compounds inhibited the polymerisation of tubulin in vitro with an 8.7-fold reduction in tubulin polymerization at 10 M for compound 7s and were shown to interact at the colchicine-binding site on tubulin, resulting in significant G2/M phase cell cycle arrest. Immunofluorescence staining of MCF-7 cells confirmed that β-lactam 7s is targeting tubulin and resulted in mitotic catastrophe. A docking simulation indicated potential binding conformations for the 3-vinyl-β-lactam 7s in the colchicine domain of tubulin. These compounds are promising candidates for development as antiproiferative microtubule-disrupting agents.

show abstract

Formation of Nitriles, Carboxylic Acids, and Derivatives by Alkylation, Acylation, and Substitution

Larock

Yao

2018

Comprehensive Organic Transformations

View full text Add to dashboard Cite

show abstract

A Simple Preparation of 3-Benzylidene-2-azetidinones

Cited by 11 publications

References 0 publications

Stereoselective Synthesis of Ezetimibe via Cross-Metathesis of Homoallylalcohols and α-Methylidene-β-Lactams

Stereoselective Synthesis of Ezetimibe via Cross-Metathesis of Homoallylalcohols and α-Methylidene-β-Lactams

3-Vinylazetidin-2-Ones: Synthesis, Antiproliferative and Tubulin Destabilizing Activity in MCF-7 and MDA-MB-231 Breast Cancer Cells

Formation of Nitriles, Carboxylic Acids, and Derivatives by Alkylation, Acylation, and Substitution

Contact Info

Product

Resources

About