Acetylepipodophyllotoxin , CAS No.1180-35-4

CAS: 1180-35-4 Cat. No.: A946597 PubChem CID: 14160030

Storage

Room temperature

仕様

保管条件

Room temperature

アクションタイプ

INHIBITOR

名前と識別子

カノニカル・スマイル

CC(=O)OC1C2COC(=O)C2C(C3=CC4=C(C=C13)OCO4)C5=CC(=C(C(=C5)OC)OC)OC

IUPAC Name

[(5S,5aR,8aR,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-5-yl] acetate

InChIKey

SASVNKPCTLROPQ-QWIYEXKTSA-N

INCHI

1S/C24H24O9/c1-11(25)33-22-14-8-17-16(31-10-32-17)7-13(14)20(21-15(22)9-30-24(21)26)12-5-18(27-2)23(29-4)19(6-12)28-3/h5-8,15,20-22H,9-10H2,1-4H3/t15-,20+,21-,22+/m0/s1

異性体SMILES

CC(=O)O[C@H]1[C@H]2COC(=O)[C@@H]2[C@@H](C3=CC4=C(C=C13)OCO4)C5=CC(=C(C(=C5)OC)OC)OC

代替CAS番号

1180-35-4

PubChem CID

14160030

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Lignans, neolignans and related compounds
    • 分類 Lignan lactones
      • Subclass Podophyllotoxins

• Kingdom: Organic compounds
• Superclass: Lignans, neolignans and related compounds
• 分類: Lignan lactones
• Subclass: Podophyllotoxins
• Intermediate Tree Nodes: Not available
• Direct Parent: Podophyllotoxins
• Alternative Parents: Aryltetralin lignans Furanonaphthodioxoles Tetralins Benzodioxoles Methoxybenzenes Phenoxy compounds Anisoles Alkyl aryl ethers Gamma butyrolactones Dicarboxylic acids and derivatives Tetrahydrofurans Carboxylic acid esters Acetals Oxacyclic compounds Organic oxides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Podophyllotoxin - 1-aryltetralin lignan - Linear furanonaphthodioxole - Naphthofuran - Tetralin - Benzodioxole - Phenoxy compound - Anisole - Methoxybenzene - Phenol ether - Alkyl aryl ether - Gamma butyrolactone - Monocyclic benzene moiety - Dicarboxylic acid or derivatives - Benzenoid - Tetrahydrofuran - Carboxylic acid ester - Lactone - Acetal - Oxacycle - Carboxylic acid derivative - Organoheterocyclic compound - Ether - Organic oxygen compound - Carbonyl group - Organic oxide - Organooxygen compound - Hydrocarbon derivative - Aromatic heteropolycyclic compound
• 説明: This compound belongs to the class of organic compounds known as podophyllotoxins. These are tetralin lignans in which the benzene moiety of the tetralin skeleton is fused to a 1,3-dioxolane and the cyclohexane is fused to a butyrolactone (pyrrolidin-2-one).
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

化学的性質と物理的性質

• 分子量: 456.400 g/mol
• XLogP3: 2.600
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 9
• Rotatable Bond Count: 6
• Exact Mass: 456.142 Da
• Monoisotopic Mass: 456.142 Da
• Topological Polar Surface Area: 98.800 Ų
• Heavy Atom Count: 33
• Formal Charge: 0
• Complexity: 729.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 4
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1

Application Protocols

No application protocols are specified for this product. This compound is supplied for general research use in chemical synthesis and analytical method development.

General handling protocols (literature/practice):

• Stock solution preparation: Dissolve in anhydrous DMSO to 10–50 mM; vortex and, if needed, gently warm (<40 °C). Filter (PTFE, 0.22 μm) for assay use.
• Analytical method development: Use reversed-phase HPLC (C18) with water/acetonitrile or water/methanol gradients, monitoring at 220–290 nm. Adjust gradient to resolve acetylated vs deacetylated congeners.
• Reaction monitoring: TLC (hexanes/EtOAc) with UV detection; confirm by LC–MS.

For specialized applications (e.g., glycosylation, acyl exchange), refer to the Reaction Conditions tab and the primary literature for detailed procedures.

Biological Roles

Context (literature/general): Epipodophyllotoxin is a plant-derived aryltetralin lignan. O-Acetylation of the phenolic OH gives acetylepipodophyllotoxin, which is commonly used as a protected intermediate in semisynthesis. While O-acetylation generally reduces phenolic reactivity, the core scaffold retains the structural motifs associated with interactions of related lignans with biomacromolecules.

• Structural motifs: benzodioxole ring, multiple methoxy substituents, and a trans-fused lactone contribute to planarity and hydrogen-bond acceptor capacity; masking of the phenol (acetate) reduces hydrogen-bond donation.
• Biochemical relevance (literature, non-clinical): The epipodophyllotoxin framework underlies several research probes that interact with topoisomerase II or microtubule-associated targets; O-acylation modulates solubility and permeability but typically serves as a protecting group rather than a bioactive enhancement per se.
• Metabolic lability: Aryl acetates can undergo esterase-mediated hydrolysis in biological milieus (literature generality), regenerating the phenolic parent; rate depends on environment and substitution.

Use note: This product is designated For research use only (from Product Data). No medical, diagnostic, or therapeutic uses are intended or implied. Any biological evaluation should be conducted under appropriate institutional approvals and safety oversight.

Buffer Applications

This small-molecule lignan ester is not a buffer component and does not serve as a pH buffering agent. It is hydrophobic and poorly soluble in aqueous buffers without co-solvent.

Practical guidance (general):

• To introduce the compound into aqueous assays, prepare a concentrated DMSO stock and dilute into the buffer with vigorous mixing, keeping final DMSO content within assay tolerances (commonly ≤0.5–1% v/v).
• If precipitation occurs, consider including a small percentage of a water-miscible co-solvent (DMSO or ethanol) and/or use surfactant systems validated for the assay. Adjust only after ensuring no interference with assay readouts.

If you require actual buffering capacity, select appropriate biological buffers (e.g., phosphate, HEPES, MOPS) independent of this compound.

Green Alternatives

While the molecule itself is fixed, greener choices can be made for its handling and transformations (literature/general guidance):

• Preferred solvents for workup/chromatography: Replace dichloromethane with ethyl acetate or 2-methyltetrahydrofuran (2-MeTHF) where solubility permits.
• Reaction media: Consider 2-MeTHF or CPME instead of THF/DCM for acylations and glycosylations; polar aprotic bio-based solvents (e.g., Cyrene) may substitute for DMF/DMSO in some coupling protocols after feasibility tests.
• Reagents: Choose carbodiimide-free acylation when possible (e.g., acid anhydrides with catalytic DMAP) to reduce urea waste; employ catalytic acyl transfer (NHC or enzymatic methods) where compatible.

Comparison snapshot (literature/general):

• DCM vs EtOAc: EtOAc offers lower toxicity and better biodegradability, though with higher boiling point and potentially slower evaporation.
• DMF vs Cyrene: Cyrene can mimic DMF polarity with improved environmental profile; viscosity and substrate solubility must be evaluated.
• THF vs 2-MeTHF: 2-MeTHF resists peroxide formation better and is sourced from renewables; minor differences in Lewis acid solvation may impact glycosylation selectivity.

Operational tips:

• Validate alternative solvent effects on glycosylation promoters (e.g., TMSOTf) and on lactone stability.
• Implement microscale solvent screening to balance yield, selectivity, and sustainability.

Pharmaceutical Uses

No excipient or pharmacopeial status is specified for this item; refer to CoA/Spec Sheet. This product is For research use only and is not intended for human or veterinary use.

Manufacturing and process chemistry context (literature/general):

• Semisynthetic precursor: Acetyl protection at the 4′-oxygen of the epipodophyllotoxin core is frequently employed during multistep syntheses to control chemoselectivity, notably in routes toward glycosylated derivatives used as research materials.
• Process considerations: The acetate improves handling by reducing phenolic acidity, aiding crystallization and chromatographic behavior. Downstream deprotection is typically achieved under mild conditions (alcoholic base or acid catalysis) to avoid lactone opening.
• Analytical control: In process development, monitoring the acetylated vs deacetylated species by HPLC/DAD and LC–MS ensures stepwise conversions and impurity tracking.

Regulatory note: Any application in cGMP manufacturing would require full specification, impurity profiling, and validated analytical methods—none of which are provided here. Consult your QA/QC group and the CoA for suitability.

Physical Properties

Item-specific specifications (this catalog entry):

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet.

Literature/general properties for acetylated epipodophyllotoxin derivatives (not product specifications):

• Physical state: typically a crystalline solid (literature).
• Solubility: sparingly soluble in water; soluble in polar aprotic organic solvents such as DMSO and DMF; moderately soluble in EtOAc, acetone, and CHCl3; limited solubility in lower alcohols (literature).
• LogP: expected in the moderate-to-high range due to multiple aryl/alkoxy groups and limited ionizable functionality (literature qualitative assessment).
• pKa: no strongly acidic/basic centers; phenolic OH is masked as an acetate ester (literature). Compound is largely neutral across physiological pH.
• UV characteristics: conjugated aromatic system exhibits UV absorbance in the 200–300 nm region; exact cutoffs/ε not specified here (literature).
• Melting point, boiling point, density, refractive index: Not specified for this item; refer to CoA/Spec Sheet. (Consult primary literature/CoA for definitive numeric values.)

Practical notes:

• Dissolve first in anhydrous DMSO or DMF to prepare concentrated stocks, then dilute with assay media/solvent as needed.
• Avoid prolonged exposure to strong base or strong acid in protic media to limit ester hydrolysis.

Quality and Grades

Item-specific quality information:

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.

Guidance on typical grades for small-molecule library compounds (general):

• Research grade: Suitable for discovery chemistry, screening, and method development. Purity typically ≥95% by HPLC/LC–MS (literature expectation), but confirm on the item’s CoA.
• Reference/analytical grade: Emphasis on identity confirmation (NMR, HRMS) and tight impurity profiles; often accompanied by detailed analytical data. If your application involves quantitative structure–activity relationships or spike-recovery studies, request the full analytical package.

Stabilizers/additives:

• None are specified for this item. If present, stabilizers would be listed on the CoA; absence is typical for neutral, solid lignan esters.

What to check on receipt:

• Identity: 1H/13C NMR consistent with the epipodophyllotoxin core and acetyl resonances; HRMS [M+H]+ consistent with the expected formula (consult CoA for exact values).
• Purity: HPLC with a diode-array detector (DAD) can exploit the strong UV absorbance of the aromatic system for impurity profiling.
• Water/peroxide/metal content: Not specified for this item; refer to CoA/Spec Sheet.

Reaction and Applications

As an O-acylated epipodophyllotoxin, this compound is primarily used as:

• Semisynthetic intermediate: The 4′-O-acetyl group serves as a protecting/activating handle for subsequent transformations on the epipodophyllotoxin core (literature). It can be selectively removed (neutral/acidic methanolysis) or displaced in glycosylation sequences.
• Reference standard: Useful in analytical method development to differentiate protected vs deprotected epipodophyllotoxin congeners (HPLC/LC–MS, DAD-based profiling).

Reaction families where it is commonly involved (literature/general):

• O-Deacylation: Mild basic (Na2CO3/MeOH) or acidic (catalytic H2SO4/MeOH) conditions to regenerate the phenolic OH; monitor to avoid lactone opening.
• Glycosylation at 4′-O: Koenigs–Knorr or modern glycosyl donors (trichloroacetimidates, thioglycosides) with promoters (TMSOTf, BF3·OEt2) to access 4′-O-glycosides on the epipodophyllotoxin scaffold.
• Chemoselective acyl migrations and re-acylations: Use of acyl chlorides/anhydrides with DMAP/Et3N for derivatization; ensure exclusion of water to prevent competitive hydrolysis.
• Oxidation/reduction at side-chain positions: Careful use of mild reagents (e.g., Dess–Martin, NaBH4) to avoid impacting the sensitive lactone and benzodioxole moieties.

Practical guidance:

• Maintain anhydrous conditions for acylation/glycosylation steps; the benzodioxole can be sensitive to strong Lewis acids—optimize promoter loading and temperature control.
• Track reactions by TLC with UV; aromatic chromophores provide strong detection. Consider LC–MS for rapid mass confirmation.

Reaction Conditions

General literature guidance for common operations on acetylated epipodophyllotoxin scaffolds (not product specifications):

• O-Deacetylation:

  • Solvent: MeOH or MeOH/CH2Cl2.
  • Reagents: NaOMe (0.05–0.2 equiv) or catalytic H2SO4 (trace) at 0–25 °C.
  • Time: minutes to a few hours; closely monitor to prevent lactone opening.

• O-Glycosylation (after deprotection or via in situ activation):

  • Donors: trichloroacetimidates or thioglycosides bearing protected sugars.
  • Promoters: TMSOTf (0.1–0.5 equiv) or BF3·OEt2 at −30 to 0 °C in dry CH2Cl2, toluene, or 2-MeTHF.
  • Notes: Control temperature and promoter loading to protect benzodioxole and lactone.

• Re-acylation/derivatization:

  • Reagents: Ac2O or acyl chlorides (1.1–1.5 equiv) with DMAP (0.05–0.1 equiv) and Et3N in CH2Cl2 or EtOAc at 0–25 °C.
  • Workup: Aqueous NaHCO3, then brine; avoid strong base.

• Oxidation of benzylic alcohols (if present in analogs):

  • Reagent: Dess–Martin periodinane in CH2Cl2 at 0–25 °C; quench with Na2S2O3/NaHCO3.

Yields and selectivity are substrate- and condition-dependent; consult primary literature for the specific derivative and scale. Always conduct small-scale trials to optimize equivalents, temperature, and time for your substrate and equipment.

Safety and Handling

Authoritative safety information resides in the SDS; always review the SDS before use.

Product-specific hazard details (as provided):

• Signal Word: Not specified for this item; refer to SDS.
• H-Statements: Not specified for this item; refer to SDS.
• GHS Classification: Not specified for this item; refer to SDS.
• Pictograms: Not specified for this item; refer to SDS.

General laboratory safety guidance for polyoxygenated lignan esters (literature/general):

• Likely harmful if swallowed or inhaled; may cause skin/eye irritation. Handle in a fume hood.
• PPE: lab coat, safety glasses, and suitable chemical-resistant gloves (e.g., nitrile). Avoid aerosol formation and dust.
• Incompatibilities: strong bases and strong acids (risk of ester hydrolysis), strong oxidizers (risk of degradation), reactive acyl-transfer catalysts in storage.
• Thermal stability: aromatic esters are generally stable at ambient temperature; avoid overheating and open flames. Decomposition may emit irritating fumes.
• First aid (overview; follow institutional protocols):
  • Inhalation: move to fresh air; seek medical attention if symptoms persist.
  • Skin/eye contact: rinse with plenty of water for at least 15 minutes; remove contaminated clothing; seek medical attention as needed.
  • Ingestion: do not induce vomiting; rinse mouth; obtain medical advice.
• Waste: Collect organic waste containing this compound as halogen-free organic waste unless mixed otherwise; dispose according to local regulations.

Storage conditions (from Product Data): Room temperature. Protect from moisture and prolonged light exposure to minimize hydrolysis/photo-degradation (general best practice).

Solvent Selection

Solubility profile (literature/general for acetylated epipodophyllotoxin derivatives):

• Highly soluble: DMSO, DMF, NMP.
• Moderately soluble: ethyl acetate, acetone, dichloromethane, chloroform, acetonitrile (warm).
• Poorly soluble: water, alkanes, very nonpolar solvents.

Polarity and handling:

• Neutral, moderately lipophilic aromatic ester; lacks strong ionizable groups. Choose polar aprotic solvents for stock solutions and reactions involving acylation, glycosylation, or coupling steps.

Practical tips:

• Prepare concentrated DMSO stocks (e.g., 10–50 mM, literature practice) and dilute into assay buffers with vigorous mixing; keep final DMSO below assay tolerance (commonly ≤0.5–1% v/v).
• For chromatography, start with hexanes/EtOAc or toluene/EtOAc gradients; consider adding 0.1–1% Et3N only if tailing is observed due to trace phenolate formation.

Comparative solvent guidance:

• DMSO vs DMF: DMSO offers better biocompatibility for screening additions; DMF may provide improved solubility for scale-up reactions but is harder to remove.
• EtOAc vs DCM: EtOAc is a greener choice and often dissolves lignans adequately; DCM provides faster evaporation and stronger elution but with higher environmental burden.
• ACN: useful for LC–MS methods; solubility may require mild warming and slow addition.

Storage and Reconstitution

Storage conditions (from Product Data):

• Store at room temperature. As general best practice for esterified lignans, keep container tightly closed, protected from moisture and prolonged light exposure.

Reconstitution and stock solutions (general guidance):

• Solvents: DMSO or DMF for concentrated stocks; ethyl acetate or acetone for preparative operations.
• Suggested stock concentrations: 10–50 mM in DMSO (literature practice). Adjust to your assay’s solubility/tolerance limits.
• Procedure: Allow vial to equilibrate to room temperature before opening to minimize moisture ingress. Weigh quickly, reseal promptly, and purge headspace with inert gas if frequent access is expected.

Stability notes (general):

• Avoid strong acids/bases and extended exposure to aqueous media to limit ester hydrolysis.
• For long-term storage of solutions, keep at −20 °C in amber vials; minimize freeze–thaw by aliquoting. Inspect for precipitation or discoloration before use.

Shipping:

• Shipped In: Not specified for this item; refer to CoA/Spec Sheet.

Research Use Note:

• For research use only (from Product Data). Not for human or veterinary use.

Structure and Identity

Brief overview: Acetylepipodophyllotoxin is an acylated aryltetralin lignan derived from the epipodophyllotoxin scaffold; it is widely used as a semisynthetic intermediate and reference compound in lignan chemistry.

• SKU: A946597
• Product Name: Acetylepipodophyllotoxin
• CAS: 1180-35-4 (literature association with acylated epipodophyllotoxin derivatives)
• CID: 14160030 (literature)
• InChIKey: 331070 (as provided; not a standard InChIKey format)
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Formula: Not specified for this item; refer to CoA/Spec Sheet. (Note: literature reports for acetylated epipodophyllotoxin derivatives commonly cite C24H24O9.)
• Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet. (Note: literature MW for acetylated epipodophyllotoxin derivatives is often ~456.4 g/mol.)

Structural features (literature description):

• Core aryltetralin lignan with a trans-fused lactone (butyrolactone) ring.
• A 1,3-benzodioxole (methylenedioxyphenyl) moiety on the aromatic A-ring.
• Multiple oxygenated substituents (methoxy/alkoxy) on the aromatic system.
• The “acetyl-” designation refers to O-acylation of a phenolic hydroxyl (commonly the 4′-OH) on the epipodophyllotoxin scaffold, yielding an aryl acetate ester.
• Stereochemistry: epipodophyllotoxin framework contains defined stereocenters at the tetralin/lactone junction (literature), typically maintained during O-acetylation. In 2D, the structure can be depicted as a substituted tetralin bearing a lactone on the side-chain, fused to an aromatic ring substituted with a benzodioxole and methoxy groups, with an acetyl ester on the phenolic oxygen.

Synthetic Utility

Key functional elements (literature/general):

• Protected phenolic oxygen (aryl acetate) enables selective O-chemistry while suppressing undesired phenolate reactivity.
• Lactone ring and benzodioxole motif are sensitive to harsh acid/base; conditions must be tuned for chemoselectivity.

Typical transformations from acetylepipodophyllotoxin:

• O-Deacetylation to epipodophyllotoxin using MeONa/MeOH or catalytic acid in MeOH; short reaction times, low temperatures to preserve the lactone.
• Formation of 4′-O-glycosides via activation with Lewis acids (e.g., TMSOTf) using trichloroacetimidate or thioglycoside donors; acetate can be displaced after in situ deprotection or via pre-deacetylation followed by glycosylation.
• Diversification through re-acylation: Installation of tailored acyl groups (e.g., pivaloyl, benzoyl) with acid chlorides/anhydrides and DMAP to modulate lipophilicity and stability.
• Late-stage oxidation/reduction: Site-selective manipulation of benzylic positions with mild reagents (Dess–Martin, TEMPO-based systems, or NaBH4 where compatible) to generate analogs.

Retrosynthetic value:

• Serves as a masked-phenol building block that preserves the stereochemical integrity of the epipodophyllotoxin core while enabling convergent attachment of O-substituents.

Tips:

• Use anhydrous, aprotic solvents; rigorously exclude water for acylation/glycosylation.
• Monitor by TLC/LC–MS; aromatic UV bands aid visualization (254 nm).

Target Specificity

No antibody, protein, or target-binding specificity is provided for this item, and none is implied. This is a small-molecule lignan ester intended for chemical research.

• Target/antigen: Not applicable.
• Clone/isotype/species reactivity: Not applicable.

If your research involves biochemical targeting (e.g., enzyme inhibition assays), establish target engagement empirically using appropriate controls and orthogonal assays.