α-Methylene-γ-butyrolactone

• CAS: 547-65-9
• Catalog Number: ACM547659
• Category: Main Products
• Molecular Weight: 98.1g/mol
• Molecular Formula: C5H6O2
• Synonyms: 3-Methylenedihydro-2(3H)-furanone, Tulipane, alpha-Methylene-gamma-butyrolactone
• IUPAC Name: 3-methylideneoxolan-2-one
• InChI: InChI=1S/C5H6O2/c1-4-2-3-7-5(4)6/h1-3H2
• InChI Key: GSLDEZOOOSBFGP-UHFFFAOYSA-N
• Boiling Point: 86-88 °C
• Density: 1.119 g/mL at 25 °C (lit.)
• Solubility: 1.53 M
• Complexity: 115
• Covalently-Bonded Unit Count: 1
• EC Number: 208-931-6
• Exact Mass: 98.036779g/mol
• Formal Charge: 0
• H-Bond Acceptor: 2
• H-Bond Donor: 0
• Heavy Atom Count: 7
• Monoisotopic Mass: 98.036779g/mol
• NSC Number: 205367
• Rotatable Bond Count: 0
• UNII: 362Y256BOL
• XLogP3: 0.8

Case Study

α-Methylene-γ-butyrolactone: A Covalent Scaffold for Novel NF-κB-Targeted Anticancer Agents

Rana, Sandeep, et al. Journal of medicinal chemistry 59.10 (2016): 5121-5127.

The discovery of new anticancer agents that effectively inhibit the pro-survival NF-κB signaling pathway remains a significant challenge in oncology. A promising strategy involves designing small molecules that covalently bind to key pathway components, such as IKKβ. This study highlights α-Methylene-γ-butyrolactone as a critical pharmacophoric core, serving as an electrophilic Michael acceptor that enables the development of potent, covalent NF-κB inhibitors.
In this drug discovery program, a focused library of compounds featuring the α-methylene-γ-butyrolactone motif was synthesized and screened for their ability to inhibit TNFα-induced NF-κB activity in cancer cells. Structure-activity relationship (SAR) studies systematically explored various substitutions and structural rigidifications to optimize potency and stability, leading to the identification of advanced spirocyclic analogues.
Key Performance of Optimized Analogues:
· Potent Pathway Inhibition: The lead spirocyclic analogue 19, incorporating the rigidified α-methylene-γ-butyrolactone core, achieved approximately 75% inhibition of NF-κB activation in cellular assays, matching the activity of a known control inhibitor (ML-120B).
· Confirmed Covalent Mechanism: Chemical proteomics confirmed that analogue 19 exerts its activity through covalent binding to both IKKβ and NF-κB, validating the design strategy centered on the reactive lactone core.
· Effective Antitumor Activity: In preclinical models, analogue 19 demonstrated single-agent efficacy by inhibiting ovarian tumor growth and showed a synergistic effect when combined with cisplatin. A subsequent optimized compound, 29, exhibited improved potency, inhibiting cancer cell growth with low-micromolar (µM) activity.

α-Methylene-γ-Butyrolactone: Enabling Novel, Broad-Spectrum Agricultural Fungicides

He, Hong-Wei, et al. Pest Management Science 79.12 (2023): 5015-5028.

Protecting crops from destructive fungi and oomycetes requires effective fungicides, yet resistance development and environmental concerns drive the need for new chemical scaffolds. In this research, the α-methylene-γ-butyrolactone group-a reactive electrophilic motif-was synthetically fused with a salicylaldehyde-derived fragment to create a novel series of hybrid molecules. This strategic design aimed to combine potential bioactivities into a single agent. The fungicidal performance of these compounds was rigorously evaluated in vitro and in vivo against key plant pathogens, including Rhizoctonia solani, Valsa mali, and Phytophthora capsici.
Key Performance of Lead Compound C3:
· Potent and Broad-Spectrum Activity: The lead compound C3 exhibited excellent in vitro efficacy, with an EC50 of 0.65 μg/mL against R. solani, outperforming pyraclostrobin (EC50 = 1.44 μg/mL) and approaching the potency of carbendazim. It also showed strong activity against V. mali (EC50 = 0.91 μg/mL) and P. capsici (EC50 = 1.33 μg/mL).
· Effective In Vivo Protection: In live plant tests, C3 provided 84.1% protective efficacy at 100 μg/mL against R. solani, superior to pyraclostrobin (78.4%). In pot experiments, its 74.8% efficacy at 200 μg/mL was comparable to the established fungicide validamycin.
· Multi-Target Mechanism of Action: Studies indicated C3 acts by disrupting fungal cell membranes, damaging ultrastructure, and binding to complex III to impair respiratory metabolism. It also effectively inhibited sclerotia germination and formation.

Chemoselective Ring-Opening Polymerization of α-Methylene-γ-butyrolactone for Sustainable and Recyclable Polyester Materials

Shen, Yong, et al. CCS Chemistry 3.1 (2021): 620-630.

This study highlights the application of α-methylene-γ-butyrolactone as the foundational building block in the first organocatalytic, chemoselective ring-opening polymerization (ROP) to produce unsaturated, fully recyclable polyesters. The key innovation was employing a binary catalyst system consisting of an organophosphazene superbase (CTPB) and a selected urea cocatalyst (U4). This system was finely tuned to activate the lactone ring for ROP while simultaneously suppressing the competing vinyl-addition polymerization, with reaction temperature being a critical control parameter.
Key Performance:
· Perfect Chemoselectivity: Under optimized conditions (CTPB/U4 catalyst, THF solvent, -50 °C), the polymerization achieved exclusive ring-opening polymerization (50% conversion) with 0% vinyl-addition byproduct, producing pure P(MBL)ROP polyester.
· Controlled Polymer Characteristics: The process yielded polymers with controlled molecular weights (e.g., Mn = 5.9 kDa) and relatively narrow dispersity (Ð = 1.29), indicating a well-controlled chain-growth mechanism.
· Complete Chemical Recyclability: The resulting polyester, P(MBL)ROP, demonstrated quantitative and selective depolymerization back to its original MBL monomer under mild chemolytic conditions, establishing a closed-loop lifecycle.
· Retained Polymer Functionality: The unsaturated exocyclic methylene group in the polymer backbone remained accessible for efficient post-polymerization modification (e.g., via thiol-ene click chemistry), enabling property tuning.