(S)-Higenamine hydrobromide , CAS No.105990-27-0

CAS: 105990-27-0 Cat. No.: S1440537 Formula: C₁₆H₁₈BrNO₃ Molecular Weight: 352.22 PubChem CID: 12313508

Storage

Store at -20°C,Desiccated

Shipped In

Ice chest + Ice pads

Overview

(S)-Higenamine ((S)-Norcoclaurine) hydrobromide, a S-enantiomer of Higenamine, is the entry compound in benzylisoquinoline alkaloid biosynthesis. (S)-Higenamine hydrobromide is produced by the condensation of dopamine and 4-hydroxyphenylacetaldehyde (4-HPAA) by norcoclaurine synthase (NCS).

Specifications

Storage

Store at -20°C,Desiccated

Shipped In

Ice chest + Ice pads

This product requires cold chain shipping. Ground and other economy services are not available.

Names and Identifiers

Canonical Smiles

C1CNC(C2=CC(=C(C=C21)O)O)CC3=CC=C(C=C3)O.Br

IUPAC Name

(1S)-1-[(4-hydroxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinoline-6,7-diol;hydrobromide

InChIKey

KNUKFIRMGSQPEM-UQKRIMTDSA-N

INCHI

1S/C16H17NO3.BrH/c18-12-3-1-10(2-4-12)7-14-13-9-16(20)15(19)8-11(13)5-6-17-14;/h1-4,8-9,14,17-20H,5-7H2;1H/t14-;/m0./s1

Isomeric SMILES

C1CN[C@H](C2=CC(=C(C=C21)O)O)CC3=CC=C(C=C3)O.Br

PubChem CID

12313508

Molecular Weight

352.22

Application Protocols

No validated in-house protocols are provided for this item. The following are general, non-binding research guidelines; adjust to your laboratory’s SOPs.

• Preparation of aqueous stock (general):
  1. Equilibrate vial to room temperature in a desiccator.
  2. Dissolve to 10–50 mM in degassed water or buffer (pH 5.5–7.0). If needed, include 0.1–1 mM ascorbate to limit oxidation.
  3. Filter through 0.22 µm for sterile applications; aliquot to minimize freeze–thaw.
• Preparation in DMSO or ethanol (general):
  1. Prepare 10–100 mM stocks under nitrogen.
  2. Store aliquots at −20°C protected from light; warm and mix before use.
• Analytical reference standard (general):
  • Dry the material under vacuum over P2O5 or in a desiccator if moisture pickup is suspected.
  • Prepare calibration curves freshly; verify peak identity by MS (positive ESI) and retention time matching.

Item-specific tested applications, recommended dilutions, and positive controls: Not specified for this item; refer to CoA/Spec Sheet.

Biological Roles

(S)-Higenamine is a benzyltetrahydroisoquinoline alkaloid encountered in several plant genera (e.g., Aconitum, Nandina) and is part of the broader benzylisoquinoline alkaloid biosynthetic network (literature). The hydrobromide is a laboratory salt form for research use.

• Biosynthetic context (literature):
  • Derived from L-tyrosine via dopamine and 4-hydroxyphenylacetaldehyde precursors through Pictet–Spengler-type enzymatic steps forming the tetrahydroisoquinoline core.
  • Intermediary role in pathways leading to diverse alkaloids; enzymatic O-methylations and oxidations diversify substitution patterns.
• Molecular features relevant to biology:
  • Catechol motif and phenolic hydroxyls underpin redox behavior and potential interactions with oxidative enzymes.
  • Protonatable amine influences transport and distribution in biological matrices (pH-dependent ionization).
• Research usage (non-clinical):
  • Employed as a reference analyte in metabolomic/natural product profiling.
  • Investigations of structure–property relationships of benzyltetrahydroisoquinolines (binding, permeability, stability) in vitro.

No medical or clinical claims are made here. All mentions are for biochemical and phytochemical research contexts only.

Buffer Applications

This product is not a buffering agent. However, as a hydrobromide salt of a basic amine, it is typically formulated for research as aqueous or mixed aqueous-organic stock solutions.

Practical guidance (general):

• Stock preparation: Dissolve in deionized water or buffer at neutral to slightly acidic pH (e.g., pH 5.5–7.0) to maintain stability of the catechol moiety. Avoid alkaline conditions that promote oxidation.
• Concentration: Prepare concentrated stocks in water, ethanol, or DMSO as appropriate for your assay, then dilute into the working buffer immediately before use.
• Antioxidants: If oxidation/discoloration is observed, include minimal amounts of an antioxidant (e.g., ascorbic acid 0.1–1 mM) in the buffer and minimize air exposure (sparge with nitrogen) (literature practice).
• Filtration: For sterile applications, pass through a 0.22 µm filter; avoid prolonged contact with reactive plastics.

Item-specific buffer compatibility and stability data: Not specified for this item; refer to CoA/Spec Sheet.

Green Alternatives

As a solid research reagent, the "greenness" considerations focus on solvent and reagent choices during handling and derivatization of (S)-higenamine hydrobromide rather than on the compound itself.

Greener solvent choices (literature/general):

• Replace chlorinated solvents with:
  • Ethyl acetate or 2-MeTHF for extractions and medium-polarity reactions
  • Methanol or ethanol for dissolution and crystallization where compatible
• For protective group chemistry on phenols:
  • Use greener bases (e.g., K2CO3) instead of strong bases where possible
  • Prefer carbonate forming reagents or enzymatic esterifications under mild conditions
• Oxidation control:
  • Employ aqueous buffers with ascorbate or minimal headspace nitrogen sparging instead of large excesses of non-green antioxidants.

Example comparison (general):

• DMSO vs ethanol for stock solutions:
  • DMSO: excellent solubilizer but persistent, difficult to remove; higher environmental burden.
  • Ethanol: renewable, lower toxicity, easy to remove but may have lower solubility limits.

Waste minimization:

• Micro-scale reactions, in-line analytical monitoring (UPLC), and solvent recycling decrease environmental footprint.

Note: These are process recommendations. No changes to the item’s composition are implied.

Pharmaceutical Uses

No pharmacopeial grade or excipient status is provided in the Product Data. This product is supplied strictly for research use only.

Research/manufacturing context (general guidance):

• Analytical reference standard: Can be used to qualify analytical methods and calibrate assays in QC environments studying benzyltetrahydroisoquinolines.
• Process development: Serves as a model substrate for developing phenolic protection/deprotection strategies or ionic salt handling protocols.
• Salt selection studies: Hydrobromide provides a comparison point for evaluating counterion effects on solubility and stability relative to HCl or sulfate salts.

Regulatory note: Absent explicit USP/EP/JP monograph or GMP statements, this material should not be used for clinical manufacturing, human administration, or diagnostic procedures.

Any claims about dosage, efficacy, or therapeutic indication are outside the scope of this research reagent and are not provided.

Physical Properties

Item-specific physico-chemical specifications are not provided in the current listing. Consult the CoA/Spec Sheet for lot-specific values.

General/literature characteristics for higenamine salts (contextual, not item-specific):

• Physical state: Typically a crystalline solid for mineral acid salts (e.g., HCl, HBr); hygroscopic tendencies are common among amine salts.
• Solubility: Hydrobromide salts of benzyltetrahydroisoquinolines are generally freely soluble in water and polar protic solvents (e.g., methanol, ethanol) and poorly soluble in nonpolar solvents.
• pKa (conjugate acid of the amine, free base reported in literature): typically in the range of 8–10 for benzyltetrahydroisoquinoline secondary amines; salt form is fully protonated in neutral water.
• LogP/logD (literature expectations): Free base moderately polar; hydrobromide salt exhibits low logD at neutral pH due to ionization.
• UV/Vis (literature): Aromatic rings and catechol motif give absorbance in the UV; exact λmax depends on ionization and medium.

Do not use the above as product specifications. For BP/MP, density, refractive index, water content, or UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.

Quality & Grades

Grade/purity is not specified in the Product Data for this catalog entry. For exact assay method, purity basis (e.g., HPLC, qNMR), counterion stoichiometry, and residual solvent content, please refer to the CoA/Spec Sheet.

Guidance on interpreting grade (general knowledge):

• Research grade: Typically suitable for exploratory synthesis, screening, and analytical reference work. Purity often reported by HPLC with area%—confirm the method and detection wavelength when comparing lots.
• Chiral designation: The product is the (S)-enantiomer. If enantiomeric excess (ee) or optical rotation is critical to your application (e.g., chiral pharmacology or asymmetric synthesis), confirm ee and [α]D values on the CoA.
• Salt content: Hydrobromide salts may be mono- or multiequivalent depending on the basic sites; confirm exact stoichiometry (e.g., 1.0 eq HBr) on the CoA for precise molarity calculations.
• Stabilizers: None stated. If stabilizers or antioxidants are used to protect phenolic motifs, they will be declared on the CoA. Absence here does not imply absence in product; verify as needed.

UV cutoffs, metal content, water content, and residual solvents: Not specified for this item; refer to CoA/Spec Sheet.

Reaction & Applications

This molecule is a versatile benzyltetrahydroisoquinoline scaffold bearing three phenolic OH groups and a secondary amine (present as a protonated ammonium in the hydrobromide). These features enable diverse transformations and research uses.

• Typical research applications (general/literature):
  • Analytical reference standard for identity/purity testing in natural product studies and QC of related materials.
  • Probe or ligand in receptor-binding or transport studies in vitro (non-clinical, research only), where enantiopurity can be critical.
  • Starting point for SAR via O-acylation/alkylation of phenols and N-alkylation to tune basicity and lipophilicity.
• Transformations enabled by functionality:
  • Phenolic chemistry: Selective protection (Boc2O/DMAP for carbonate, benzylation, silylation) to manage catechol reactivity; subsequent acylations, etherifications, or oxidative coupling to biaryls.
  • Amine derivatization: Formation of amides, ureas, or quaternary ammonium salts; reductive amination at the benzylic position is also a strategic handle in related scaffolds.
  • Oxidation state control: Catechol can undergo oxidation to o-quinone; chemoselective oxidation or in situ antioxidants (e.g., ascorbate) can be leveraged.
• Practical tips:
  • Minimize exposure to air and base to avoid catechol oxidation; perform manipulations under nitrogen/argon when feasible.
  • For coupling reactions, protect phenols first to prevent side reactions and improve solubility in organic media.
  • Track enantiomeric integrity if chiral centers are at risk (e.g., under strong acid/base or high temperature).

All uses are for laboratory research; no clinical or diagnostic use is intended.

Reaction Conditions

General literature guidance for manipulating benzyltetrahydroisoquinoline catechols like (S)-higenamine (conditions are illustrative; optimize per application):

• Liberation of free base: Dissolve the hydrobromide in water, basify to pH ~10 with NaHCO3/Na2CO3, extract with EtOAc, dry (Na2SO4), and use immediately under inert atmosphere to limit oxidation.
• O-Protection (phenols):
  • Benzylation: BnBr (1.2–2.0 eq), K2CO3, DMF or acetone, 0–25°C, 2–12 h; hydrogenolysis for deprotection.
  • Silylation: TBSCl (1.5–2.0 eq per OH), imidazole, DMF, 0–25°C; deprotect with TBAF or acid.
  • Carbonates/carbamates: Boc2O or chloroformates with DMAP, 0–25°C.
• N-Acylation: Acyl chloride or HATU-mediated coupling in DMF/CH2Cl2 with base (DIPEA), 0–25°C; protect phenols first to improve selectivity.
• Oxidation control: Add 0.1–1.0 equiv ascorbate or employ deoxygenated solvents; maintain pH ≤7 during aqueous manipulations.
• Analytical monitoring: LC–UV at phenolic/aromatic wavelengths; MS in positive mode due to protonatable amine.

Typical yields (literature ranges): O-protection and N-acylation steps often provide moderate to high yields (60–90%) when moisture/oxygen are controlled and phenols are differentially protected. These values are general and not item-specific specifications.

Safety & Handling

No GHS hazard classification is provided in the current Product Data. Always consult the SDS for authoritative safety information.

• GHS signaling, pictograms, H/P statements: Not specified for this item; refer to SDS.
• General laboratory precautions (good practice):
  • Wear appropriate PPE: lab coat, safety glasses, and chemical-resistant gloves.
  • Handle powders carefully to minimize dust generation; use a fume hood when weighing/dispensing.
  • Avoid contact with strong oxidizers; phenolic compounds can undergo oxidation, especially under basic or aerobic conditions.
• Incompatibilities (general):
  • Strong bases (may accelerate phenolic oxidation and cause discoloration)
  • Strong oxidizing agents (risk of exothermic reactions/oxidation of catechol moiety)
  • Moisture (amine salts can be hygroscopic; follow desiccated storage)
• First-aid overview (general guidance; defer to SDS):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin/eye contact: Rinse with water for at least 15 minutes; remove contaminated clothing; seek medical advice if irritation persists.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Fire-fighting (general): Organic solids may burn; use water spray, CO2, dry chemical, or foam; wear self-contained breathing apparatus.
• Waste disposal: Dispose according to institutional, local, and national regulations; avoid release to the environment.

Research use only. Not for human or veterinary use.

Solvent Selection

(S)-Higenamine hydrobromide is an ionic organic salt; solvent choice should reflect its polarity and functional group sensitivity.

• Polarity/miscibility (literature/general):
  • Expected to be freely soluble in water; also soluble in polar protic solvents (methanol, ethanol) and some polar aprotics (DMSO).
  • Poorly soluble in nonpolar solvents (hexanes, toluene) in the salt form.
• Practical recommendations:
  • For biological assays or stock solutions: Use water or buffer at neutral pH; filter-sterilize if needed. Avoid basic pH that can promote catechol oxidation.
  • For organic synthesis or derivatization: Dissolve in MeOH, EtOH, or DMSO. If the free base is required for organic-phase reactions, liberate it by basification and extract into a suitable organic solvent (e.g., ethyl acetate), then dry and use immediately to minimize oxidation.
  • For LC methods: Aqueous mobile phases with acid modifiers (e.g., 0.1% formic acid) aid retention/reproducibility and suppress on-column oxidation.
• Comparison notes:
  • Hydrobromide vs free base: The salt offers superior aqueous solubility and handling, whereas the free base may be preferred for reactions in less polar media.
  • Methanol vs DMSO: MeOH is greener and volatile (facilitates removal); DMSO allows high-concentration stocks but is higher boiling and more persistent.

Always test solubility with your specific lot; item-specific solubility is not provided here.

Storage & Reconstitution

Follow item-specific storage instructions to maintain integrity of the catechol-containing, amine salt.

• Storage (from Product Data): Store at −20°C, desiccated.
• Shipping (from Product Data): Shipped in ice chest with ice pads.
• Container handling: Reseal promptly after use; purge headspace with inert gas if practical. Protect from moisture and prolonged exposure to air.
• Light/oxidation: Catechol groups are susceptible to oxidation; store in amber vials or protected from light. Inclusion of oxygen scavengers/desiccants in secondary packaging is advisable.
• Reconstitution (general guidance):
  • Aqueous: Dissolve in cold, degassed water or buffer at pH 5.5–7.0 with gentle mixing. For long-term aqueous storage, prepare aliquots, flush with nitrogen, and freeze.
  • Organic: For high-concentration stocks, use ethanol or DMSO; aliquot and store at −20°C.
• Freeze–thaw: Minimize cycles; prefer single-use aliquots. Inspect solutions for discoloration or precipitate; discard if significant changes are observed.
• Stability data (item-specific): Not specified for this item; refer to CoA/Spec Sheet for any available shelf-life or retest date.

Research Use Only: Not for human or veterinary use.

Structure & Identity

Chiral benzyltetrahydroisoquinoline alkaloid presented as the hydrobromide salt of the (S)-enantiomer.

• Product name: (S)-Higenamine hydrobromide
• SKU: S1440537
• CAS: 105990-27-0
• Category: Small molecule compound (alkaloid salt)
• Enantiomeric form: (S) configuration at the benzylic stereocenter (literature)
• Structural features (literature):
  • Core: 1,2,3,4-tetrahydroisoquinoline ring system
  • Substituents: 6,7-dihydroxy pattern on the isoquinoline A-ring; benzyl substituent bearing a para-hydroxy group
  • Functional groups: secondary amine (protonated in the hydrobromide), three phenolic OH groups
  • Salt form: hydrobromide (protonated amine with Br− counterion)
• 2D description (literature): A tetrahydroisoquinoline fused bicyclic scaffold with two adjacent phenolic hydroxyls (catechol motif) and a benzylic side chain terminating in a p-hydroxyphenyl ring; the benzylic carbon is stereogenic and in the (S) configuration.

Item-specific identifiers:

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

Note: Literature commonly refers to “higenamine” as the free base; salt properties differ from the free base. Always match identifiers to the hydrobromide salt and (S)-enantiomer when ordering or comparing data.

Synthetic Utility

(S)-Higenamine hydrobromide is a chiral, polyfunctional scaffold useful for exploring structure–activity relationships and for constructing more complex alkaloid derivatives.

Key reactivity handles (literature/general):

• Three phenolic OH groups: Enable selective O-protection (benzyl, silyl, carbonate), O-alkylation, and ester formation; differential protection allows orthogonal manipulations.
• Secondary amine: Amenable to N-acylation, N-alkylation, and quaternization; salt form facilitates handling/solubility for aqueous-phase transformations.
• Benzylic stereocenter: Retains (S) configuration under mild conditions; racemization risk increases under strong acid/base or elevated temperature—monitor with chiral HPLC.

Strategic transformations:

• Convert hydrobromide to free base for nonpolar reactions; protect catechol as acetonide or silyl ethers to suppress oxidation and improve solubility in aprotic solvents.
• Build biaryl or diaryl ethers via oxidative coupling of protected phenols (e.g., hypervalent iodine reagents) to access higher-order alkaloid frameworks.
• Install reporter tags (fluorophores, biotin) through amide or carbamate linkages for probe development.

Utility in retrosynthesis:

• Serves as a late-stage intermediate for libraries of benzyltetrahydroisoquinolines, allowing rapid diversification at O- and N-sites while conserving the chiral core.

Target Specificity

This product is a small-molecule alkaloid, not an antibody or affinity reagent. No target specificity, clone, isotype, or species reactivity data apply.

• Item-specific target/binding data: Not specified for this item; refer to primary literature for in vitro binding studies if relevant to your research.

Frequently Asked Questions

How should this product be stored?

Store at ?20 °C, desiccated. Keep the container tightly closed with desiccant — the material is moisture-sensitive.

How is this product shipped?

This product ships in an insulated container with ice pads. Unpack on arrival and transfer it to the storage condition stated above.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 105990-27-0, the molecular formula is C16H18BrNO3, and the molecular weight is 352.22 g/mol. InChIKey KNUKFIRMGSQPEM-UQKRIMTDSA-N.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.