Rotundifolone , CAS No.3564-96-3

CAS: 3564-96-3 Cat. No.: R976985 Formula: C₁₀H₁₄O₂ Molecular Weight: 166.220

Storage

Room temperature

Specifications

Storage

Room temperature

Action Type

INHIBITOR

Names and Identifiers

Canonical Smiles

CC(=C1CC[C@]2([C@@H](C1=O)O2)C)C

IUPAC Name

(1S,6S)-6-methyl-3-propan-2-ylidene-7-oxabicyclo[4.1.0]heptan-2-one

InChIKey

AKASWINDKIEEBO-ZJUUUORDSA-N

INCHI

1S/C10H14O2/c1-6(2)7-4-5-10(3)9(12-10)8(7)11/h9H,4-5H2,1-3H3/t9-,10+/m1/s1

Molecular Weight

166.220

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Oxepanes

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Oxepanes
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Oxepanes
• Alternative Parents: Ketones Oxacyclic compounds Epoxides Dialkyl ethers Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aliphatic heteropolycyclic compounds
• Substituents: Oxepane - Ketone - Oxacycle - Ether - Oxirane - Dialkyl ether - Organic oxygen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Carbonyl group - Aliphatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as oxepanes. These are compounds containing an oxepane ring, which is a seven-member saturated aliphatic heterocycle with one oxygen and six carbon atoms.
• External Descriptors: Cyclic monoterpenes

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

Chemical and Physical Properties

• Molecular Weight: 166.220 g/mol
• XLogP3: 1.800
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 0
• Exact Mass: 166.099 Da
• Monoisotopic Mass: 166.099 Da
• Topological Polar Surface Area: 29.600 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 274.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 2
• 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 proprietary or validated bioassay protocols are provided for this item. Typical research uses include:

• GC–MS reference standard

  • Prepare a 1–10 mg/mL stock in hexane or ethyl acetate. Inject 0.2–1 µL with a nonpolar capillary column (e.g., 5% phenyl methylpolysiloxane). Use a temperature program suitable for monoterpenes (e.g., 50 → 220 °C at 3–5 °C/min). Determine retention index vs n-alkanes.

• Stock solutions for in vitro assays (general)

  • Dissolve in DMSO or ethanol to 100–1000 mM; vortex and sonicate if needed. Dilute into assay buffer/media ensuring final solvent ≤1% v/v. Due to hydrophobicity, include nonionic surfactant (e.g., 0.01–0.1% Tween 80) if precipitation occurs.

• Derivatization example

  • Epoxidation: Dissolve rotundifolone (1.0 equiv) in dry DCM (0.05–0.1 M), cool to 0 °C, add mCPBA (1.2 equiv) portionwise with NaHCO3 buffer. Stir 1–2 h, quench with saturated Na2S2O3/NaHCO3, extract, dry, and purify by flash chromatography (hexanes/EtOAc).

These are general literature-style procedures, not validated methods for this specific lot. Always optimize for your laboratory setup and consult the CoA/SDS prior to use.

Biological Roles

General literature context (not product-specific):

• Origin and biosynthesis

  • Rotundifolone is reported as a prominent constituent of essential oils from certain Mentha taxa (e.g., Mentha x villosa). Biosynthesized via the plastidial MEP (2-C-methyl-D-erythritol 4-phosphate) pathway, it derives from the universal monoterpene precursors geranyl pyrophosphate (GPP) through cyclization and subsequent oxidation/isomerization steps.

• Ecological function

  • Monoterpenes serve as allelochemicals and signaling agents in plant–insect interactions. Enone-containing monoterpenes can deter herbivory and exhibit antimicrobial effects in ecological contexts (literature), though such activities are not claimed for this product.

• Metabolism

  • In biological systems, phase I metabolism often includes reduction of the enone or epoxidation of the C=C, followed by phase II conjugation (glucuronidation/sulfation). Enzymes like aldo-keto reductases and cytochrome P450s are implicated (literature/general).

• Analytical/biochemical use

  • Employed as a reference standard for chemotaxonomic profiling of mint oils by GC–MS and as a substrate in studies of enone-reactive enzymes or glutathione conjugation (Michael acceptor) in vitro.

Note: Rotundifolone from Aladdin Scientific is supplied strictly for research use only. No biological efficacy or clinical performance is implied.

Buffer Applications

Not typically applicable. Rotundifolone is a hydrophobic monoterpene ketone and is not used as a buffering agent. For aqueous work, it is generally dissolved in a miscible co-solvent (e.g., ethanol, DMSO) and then diluted into buffered media if required for in vitro assays. Refer instead to Solvent Selection and Reaction & Applications for practical handling guidance.

Green Alternatives

Considerations are twofold: (a) greener solvents for handling rotundifolone and (b) greener routes if synthesizing or modifying it. The compound itself is a bio-based monoterpenoid and may be obtainable from renewable essential oils.

• Greener handling solvents (general)

  • Prefer bio-based ethanol or 2-methyltetrahydrofuran (2-MeTHF) over chlorinated solvents when compatible with the task.
  • Ethyl acetate and supercritical CO2 (for extraction) are greener alternatives to hexane/CH2Cl2.

• Example comparison (general guidance)

  • Chlorinated solvents (DCM): High solvency, easy workups; environmental and health concerns, halogenated waste.
  • Ethyl acetate: Good solvency for monoterpenes; biodegradable, lower toxicity; slightly higher boiling point.
  • 2-MeTHF: Biomass-derived, useful for conjugate additions; forms fewer peroxides than THF and has favorable phase behavior for extractions.
  • Heptane/isohexane: Lower toxicity vs hexane (n-hexane neurotoxicity concerns); good for nonpolar work.

• Synthesis/derivatization (general)

  • Biocatalysis (ene-reductases, Baeyer–Villiger monooxygenases) in aqueous/green media can transform the enone under mild conditions.
  • Photocatalytic methods under visible light (organophotocatalysts) can replace stoichiometric reagents for certain reductions or conjugate additions.

Trade-offs

• Greener solvents may alter selectivity or rates (e.g., 2-MeTHF vs THF in Michael additions). Validate with small-scale trials.
• Avoid excessive heating and use energy-efficient evaporation (rotary evaporators with good vacuum) to reduce energy footprint.

Pharmaceutical Uses

This product is for research use only. No clinical or therapeutic claims are made.

• General formulation context (literature/general)

  • Monoterpenes/enones like rotundifolone may be studied as flavor/fragrance components or penetration enhancers in non-therapeutic formulation research; however, rotundifolone is not a compendial excipient and has no established pharmacopeial monograph to our knowledge.
  • In preformulation-style studies, hydrophobic terpenoids are typically handled in ethanol, propylene glycol, PEG 400, or lipid vehicles. Solubility in purely aqueous media is poor; surfactant systems (e.g., polysorbates) can be used to disperse.

• Manufacturing/analytical aspects

  • As a reference standard for raw-material identity tests of Mentha-derived essential oils by GC–MS/GC–FID.

Item-specific status

• Pharmacopeia listing/grade: Not specified for this item; refer to CoA/Spec Sheet.
• Residual solvent/heavy metal specs: Not specified for this item; refer to CoA/Spec Sheet.

Physical Properties

Only limited item-specific physical data are provided for this catalog entry.

• Item-specific values (from Product Data)

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

• Typical physical properties (literature/general; not item specifications)

  • Physical state: Colorless to pale yellow liquid typical of monoterpene ketones.
  • Odor: Minty/camphoraceous, consistent with Mentha-derived monoterpenes.
  • Solubility: Low in water; miscible with common organic solvents such as ethanol, diethyl ether, dichloromethane, hexanes (literature).
  • Volatility: Moderate; behaves similarly to carvone/piperitenone-class monoterpenes (literature).
  • Refractive index and density: Typically in the range reported for monoterpene ketones; exact values vary with composition and temperature (literature). Not specified for this item; refer to CoA/Spec Sheet.
  • Boiling point and melting point: Reported in literature for rotundifolone; not established here as item specifications. Not specified for this item; refer to CoA/Spec Sheet.
  • LogP: Expected >2 reflecting hydrophobic monoterpene framework (literature). Not specified for this item; refer to CoA/Spec Sheet.

Notes

• All literature values are provided for general context only. For precise, lot-specific physical constants (e.g., refractive index, density), consult the CoA/Spec Sheet for SKU R976985.

Quality & Grades

• Item-specific quality data (from Product Data)

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

• Guidance on grades for monoterpenoid ketones (general)

  • Research grade: Suitable for exploratory synthesis, reference standards, and mechanistic studies. May have broader impurity profile than analytical grades.
  • Analytical/HPLC grade: Controlled UV background and impurity profile for chromatographic work; useful when rotundifolone is used as a calibration/reference material.
  • Natural product vs synthetic: Rotundifolone can be isolated from essential oils or prepared synthetically. Source impacts minor terpene impurities and enantiomeric composition. For chiral or trace-analysis work, request enantiomeric excess (ee) and source documentation.

• Quality attributes to review on the CoA/Spec Sheet (recommendations)

  • Identity confirmation: 1H/13C NMR, IR (C=O near 1670–1705 cm−1 typical), GC–MS with library match, HRMS.
  • Purity: GC or HPLC area% and reporting of related monoterpenes (e.g., piperitenone-class) if present.
  • Physical constants: Refractive index (nD), density at 20 °C, appearance, and odor description.
  • Stability: Any antioxidant/stabilizer use (e.g., BHT) should be declared if applicable; for this item, stabilizers are not specified and should be verified on the CoA.

Note: Where specific values are not stated in the Product Data, treat them as Not specified for this item; refer to CoA/Spec Sheet.

Reaction & Applications

As an α,β-unsaturated monoterpene ketone, rotundifolone is a versatile synthon and reference compound in natural products and terpene chemistry (literature/general). Typical research uses include:

• Conjugate (Michael) additions

  • Soft nucleophiles (thiols, malonates, amines) add at Cβ under base or Lewis acid catalysis. Copper or organocatalysts can promote 1,4-selectivity.

• Selective reductions

  • Chemoselective hydrogenation (Pd/C) reduces the C=C to saturated ketone; conjugate reduction (Stryker’s reagent, Hantzsch ester/photoredox) yields the enolate-derived products.
  • Carbonyl reduction (NaBH4, CBS, or SmI2 conditions) affords allylic alcohols; stereochemical outcomes depend on approach and ring conformation.

• Epoxidation and dihydroxylation

  • Peracids (mCPBA) epoxidize the enone C=C; subsequent ring opening gives β-hydroxy ketones. Enantioselective variants employ chiral dioxiranes (literature).

• Halogenation and conjugate additions

  • NBS under radical or ionic conditions furnishes allylic bromides; 1,4-addition of organocuprates extends the skeleton.

• Photochemistry and cycloadditions

  • Enone [2+2] photocycloadditions under UV furnish bicyclic adducts; Diels–Alder reactions with suitable dienes/dienophiles can remodel the terpene core.

• Applications in research

  • Calibration/marker for Mentha essential oils by GC–MS.
  • Starting point for semisynthesis of related natural products (e.g., piperitenone derivatives) and for SAR exploration of enone-containing scaffolds (non-clinical research).

Practical tips

• Minimize base strength and temperature to limit self-aldol/polymerization.
• Work under inert atmosphere for sensitive transformations; dry solvents improve reproducibility.
• For GC–MS quantitation, employ internal standards (e.g., isopropyl myristate or terpenes with distinct retention indices).

Reaction Conditions

Representative conditions for enone transformations of monoterpenoids (literature/general guidance; optimize for your system):

• Conjugate (Michael) additions

  • Nucleophiles: Malonates, thiols, amines, organocuprates
  • Catalysis: Cu(I) salts (e.g., CuBr·SMe2, 5–20 mol%), Lewis acids (BF3·OEt2, 0–5 °C), or secondary amine organocatalysts (10–20 mol%)
  • Solvents: THF, 2-MeTHF, toluene, DCM; 0 to 25 °C; 1–12 h

• Carbonyl reductions

  • NaBH4 (1–2 equiv) in MeOH/EtOH at 0–25 °C, 0.5–2 h to give allylic alcohol
  • Stereoselective: CBS catalyst (5–10 mol%) with borane in toluene/THF, −20 to 0 °C

• Conjugate reductions

  • Stryker’s reagent ([(Ph3P)CuH]6, 5–10 mol%) in toluene/THF, 0–25 °C; or Hantzsch ester (2–3 equiv) with Ir/Ru or organic photoredox catalyst under blue LEDs

• Epoxidation

  • mCPBA (1.1–1.5 equiv) in DCM at 0 °C to rt, 1–3 h; buffer with NaHCO3 to control acidity

• Baeyer–Villiger oxidation

  • mCPBA (2–3 equiv) or peracetic acid in DCM/CHCl3, 0–25 °C; or enzymatic BVMO in aqueous buffer with cosolvent

• Hydrogenation

  • Pd/C (5–10 wt%) in EtOH/EtOAc under 1–3 bar H2, rt to 40 °C, 2–8 h; monitor to avoid overreduction

• Photocycloaddition

  • UV-A (350–365 nm) in nonpolar solvent (cyclohexane/toluene), 0–25 °C, dilute (≤0.02 M) to suppress polymerization

Notes

• Use inert atmosphere when moisture/oxygen compromise selectivity.
• For scale-up, control exotherms with portionwise oxidant/reductant addition.
• Reported yields vary widely (50–90%) depending on substitution and conditions; verify by small-scale trials.

Safety & Handling

Safety data specific to this item are not provided in the Product Data. Handle according to good laboratory practice and consult the SDS for authoritative guidance.

• Item-specific hazard information (from Product Data)

  • Signal word: Not specified for this item; refer to SDS.
  • H-statements: Not specified for this item; refer to SDS.
  • GHS classification/pictograms: Not specified for this item; refer to SDS.

• General safety considerations for monoterpene enones (literature/general)

  • Flammability: Many monoterpenes are combustible liquids with low flash points; keep away from ignition sources, use in a fume hood.
  • Irritation/Sensitization: α,β-Unsaturated ketones may cause skin/eye irritation and can be sensitizers in susceptible individuals; avoid contact.
  • Inhalation: Volatile; avoid inhalation of vapors. Provide adequate ventilation.
  • Environmental: Avoid release to the environment; terpenoids can be toxic to aquatic organisms at sufficient concentrations.

• Incompatibilities and stability (general)

  • Incompatible with strong oxidizers, strong bases/acids (can promote unwanted aldol or polymerization pathways), and reducing agents.
  • Enones can undergo polymerization or Michael addition with nucleophiles; store in tightly closed containers to limit adventitious reactions.
  • Light/air: Prolonged exposure may promote oxidation; store protected from light and air where possible.

• PPE and first aid (general)

  • PPE: Lab coat, nitrile gloves, splash goggles. Consider organic vapor-rated fume hood.
  • First aid: Rinse skin/eyes with water for at least 15 minutes upon contact; remove contaminated clothing. If inhaled, move to fresh air. Seek medical attention as needed.

Note: Always defer to the specific SDS for SKU R976985 for definitive hazard classification, exposure limits, and response measures.

Solvent Selection

Rotundifolone is a nonpolar-to-moderately polar organic liquid (terpenoid enone). Solvent choice depends on application (isolation, reaction, analysis).

• Polarity and miscibility (literature/general)

  • Polarity class: Low polarity with a polarizable carbonyl; behaves similarly to carvone/piperitenone in solvent dependence.
  • Water: Sparingly soluble; not miscible.
  • Miscible/soluble in: Ethanol, methanol (good), acetone, ethyl acetate, diethyl ether, dichloromethane, toluene, and alkanes (hexanes) to varying extents.

• Use-case guidance

  • Preparative handling: Hexanes/ethyl acetate or pentane/ether systems suit flash chromatography of terpenoids.
  • Spectroscopy: CDCl3 or C6D6 for NMR; dilute solutions minimize self-association and polymerization. For IR, neat ATR or solution in hexane/CH2Cl2.
  • Synthesis: Polar aprotic solvents (THF, MeCN, DMSO) support conjugate addition; nonpolar solvents (toluene, heptane) are useful for selective oxidations or radical additions.
  • Analytical: GC–MS is preferred (volatile, thermally stable under typical GC conditions). For LC–UV, use MeCN/H2O with low % acidic modifier; monitor at 210–230 nm (enone absorbance) (literature guidance).

• Comparison (general)

  • Versus highly polar ketones (e.g., cyclohexanone): Rotundifolone requires less polar eluents and shows higher GC volatility.
  • Versus hydrocarbons (e.g., limonene): Increased solubility in polar aprotics and stronger UV response due to enone.

Storage & Reconstitution

• Item-specific storage conditions (from Product Data)

  • Storage: Room temperature.
  • Shipped in: Not specified for this item; refer to CoA/Spec Sheet.

• General storage guidance for monoterpene enones

  • Keep container tightly closed under an inert headspace (nitrogen/argon) if feasible to slow oxidation and evaporation.
  • Store in amber glass to protect from light; secondary containment helps contain odors and prevent cross-contamination.
  • Avoid prolonged exposure to air, heat, and moisture. If long-term storage is planned, consider refrigeration (2–8 °C) despite room-temperature stability to further preserve quality; verify no crystallization/precipitation occurs (usually a liquid).

• Reconstitution and handling

  • If provided neat, use as received. For stock solutions, prepare in dry organic solvents (e.g., ethanol, DMSO, ethyl acetate, hexane) at desired concentrations. Label with solvent, concentration, and date.
  • For analytical reference solutions (GC–MS), prepare 1–10 mg/mL in hexane or EtOAc and store at 2–8 °C in sealed vials; minimize headspace and limit freeze–thaw/evaporation cycles.

• Stability notes

  • Monitor by GC or 1H NMR for signs of oxidation/polymerization (new signals, broadened baselines). Discard if significant decomposition is observed.

Where a specific value or condition is not listed in Product Data, treat it as Not specified for this item; refer to CoA/Spec Sheet.

Structure & Identity

Brief overview: Rotundifolone is a plant-derived monoterpenoid ketone commonly reported as a major constituent of certain Mentha (mint) essential oils (literature). For this catalog item, only limited identifiers are specified.

• Item-specific identifiers (from Product Data)

  • SKU: R976985
  • Product name: Rotundifolone
  • CAS: 3564-96-3
  • CID (PubChem): 442497
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet. (Provided string “7558” is not a valid InChIKey.)
  • SMILES: 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.

• Structural features (general/literature description)

  • Class: Monoterpenoid (C10) bearing a conjugated enone (α,β-unsaturated ketone) within a cyclohexene framework (literature).
  • Functional groups: Enone (C=C–C=O), isopropenyl-like terpenoid side chain (literature). No heteroatoms beyond the carbonyl oxygen are typically present.
  • Stereochemistry: Reported rotundifolone can exhibit defined stereochemistry at ring junction carbons depending on biosynthetic origin; commercial materials may be racemic or enantiomerically enriched (literature). Specific stereochemical purity for this item: Not specified for this item; refer to CoA/Spec Sheet.

• 2D structure (verbal, literature-based)

  • A six-membered cyclohexene ring containing a carbonyl (enone) and a pendant isoprenoid substituent; conjugation runs across the ring double bond into the carbonyl, characteristic of monoterpene enones.

Synthetic Utility

Rotundifolone’s α,β-unsaturated ketone within a terpenoid scaffold enables diverse synthetic manipulations and SAR diversification (literature/general):

• Functional group interconversions

  • 1,2- vs 1,4-reduction control accesses allylic alcohols or saturated ketones; hydrogenation establishes stereocenters on the ring.
  • Baeyer–Villiger oxidation affords lactones; subsequent hydrolysis or reduction provides diols and hydroxyacids.

• Carbon–carbon bond formation

  • Organocuprate and conjugate addition of carbon nucleophiles at Cβ extends the carbon skeleton; tandem Michael–aldol sequences construct bicyclic frameworks.
  • Photoredox-mediated Giese additions to the enone enable late-stage functionalization under mild conditions.

• Electrophilic additions and rearrangements

  • Halofunctionalization (NBS/NCS) allows allylic/benzylic functionalization; rearrangements under acidic conditions can rearrange the terpene core (Wagner–Meerwein-type).

• Chiral pool/derivatization

  • If enantiomerically enriched, serves as a chiral pool synthon; auxiliary-controlled reductions or organocatalytic conjugate additions enable diastereodivergent outcomes.

• Analytical/synthetic benchmark

  • Useful as a GC–MS retention-index marker among monoterpene enones; aids in profiling Mentha chemotypes and validating isolation/synthesis workflows.

Practical notes

• Control temperature and base strength to avoid self-condensation/polymerization.
• Dry, oxygen-limited conditions often improve selectivity in conjugate additions and epoxidations.
• Protect the enone when needed (e.g., as ketal) to direct reactivity elsewhere on the molecule.

Target Specificity

Not applicable. Rotundifolone is a small-molecule monoterpenoid, not a biological targeting reagent or antibody. No antigen/epitope specificity, clone, isotype, or species reactivity applies to this product.