((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) (ALC‑0315) is a synthetic ionizable amino lipid that plays a critical role in the formation of lipid nanoparticles (LNPs) for mRNA vaccine delivery. As a component of the Pfizer/BioNTech BNT162b2 (Comirnaty®) SARS‑CoV‑2 mRNA vaccine, ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) ensures efficient vaccine assembly, protects the mRNA from premature degradation, and promotes the release of the nucleic acid into the cytoplasm for further processing after endocytosis. Structurally, ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) features four branched saturated alkyl tails linked via biodegradable ester bonds to a central ionizable amine headgroup, endowing it with a cone‑shaped molecular geometry that facilitates endosomal membrane destabilization. In LNP formulations, ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) is combined with DSPC, cholesterol, and PEG‑lipid (ALC‑0159) at a molar ratio of 46.3:9.4:42.7:1.6 to produce the commercial vaccine.
|
Parameter |
Specification |
|
Product Name |
((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) |
|
CAS Number |
2036272-55-4 |
|
Molecular Formula |
C₄₈H₉₅NO₅ |
|
Molecular Weight |
766.27 g/mol |
|
Appearance |
Colorless to yellowish liquid |
|
Boiling Point |
760.6±55.0 °C at 760 mmHg (predicted) |
|
Density |
0.919±0.06 g/cm³ (predicted) |
|
Solubility |
DMSO: 50 mg/mL; Ethanol: 80–100 mg/mL; Chloroform: 50 mg/mL |
|
Storage Condition |
2-8°C, protect from light |
|
pKa |
15.11±0.01 |
((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) is one of only three ionizable cationic lipids currently in clinically approved RNA therapeutic products, serving as the functional ionizable lipid component of the Pfizer/BioNTech BNT162b2 (Comirnaty®) SARS‑CoV‑2 mRNA vaccine. Its proven safety and efficacy in billions of administered doses validates its performance for mRNA delivery.
The tertiary amine headgroup in ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) is neutral at physiological pH, minimizing non‑specific toxicity, but becomes positively charged in acidic endosomes (pH ~5.0–6.5). This pH‑dependent protonation triggers endosomal membrane destabilization, enabling efficient cytosolic release of encapsulated nucleic acid payloads.
The four branched saturated alkyl tails linked via ester bonds to a central ionizable amine headgroup in ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) create a cone‑shaped molecular geometry. This shape promotes the formation of inverse hexagonal (H₂) phases within endosomal membranes—a structural feature directly correlated with enhanced endosomal escape and transfection potency.
Beyond SARS‑CoV‑2 vaccines, ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) has been successfully employed in preclinical studies for influenza mRNA vaccines, personalized cancer vaccines, and gene therapy applications. Its validated performance across diverse nucleic acid payloads (mRNA, saRNA, circRNA, siRNA) makes it a preferred ionizable lipid for next‑generation LNP therapeutics.
Cosperpharm supplies ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) with full analytical characterization—including HPLC purity, ¹H NMR, MS, water content, and residual solvent analysis. DMF‑ready documentation packages, stability summaries, and custom quality agreements are available to support your IND, NDA, or ANDA filings.
The synthesis of ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) (ALC‑0315) has been described in the literature, and a simplified two‑step route has recently been proposed for economic manufacturing.
2‑Hexyldecanoic acid is reacted with a fourfold excess of 1,6‑dibromohexane in DMF in the presence of potash (K₂CO₃). The reaction mixture is stirred at room temperature for three days. The condensation reaction product is isolated by chromatography on silica gel with 85% yield. Dibromohexane recovery rate is 52%.
The bromoalkyl ester intermediate is then reacted with 4‑aminobutanol in the presence of a reducing agent (e.g., sodium triacetoxyborohydride) to form the final tertiary amine structure. The target product is purified by chromatography on a silica gel column using a methanol gradient in methylene chloride to yield ALC-0315.
Each batch undergoes:
● Gas chromatography (GC) – purity ≥97.0%
● Non‑aqueous titration – purity ≥97.0%
● Refractive index – confirmatory analysis
● ¹H NMR – structural verification
● Appearance – colorless to light yellow to light orange clear liquid
A comprehensive COA, MSDS (with full GHS information), and certificate of origin accompany every shipment.
Ready to secure your supply of ALC‑0315 for mRNA vaccine development or commercial manufacturing? Cosperpharm delivers consistent quality, regulatory‑ready documentation, and flexible volumes from R&D to commercial scale. Contact our team today to discuss your requirements, request a quote, or schedule a technical consultation.
Address
No. 2 Yangguang 3rd Road, Duodao Chemical Cycle Industrial Park, Jingmen City, Hubei Province, China
Tel
![1-[2,3-Bis[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]propyl]pyrrolidine](/upload/8820/1-2-3-bis-9z-12z-octadeca-9-12-dien-1-yloxy-propyl-pyrrolidine-349384.webp "1-[2,3-Bis[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]propyl]pyrrolidine")
![1,2,4-Triazolo[4,3-a]pyridin-3(2H)-one](/upload/8820/1-2-4-triazolo-4-3-a-pyridin-3-2h-one-440735.webp "1,2,4-Triazolo[4,3-a]pyridin-3(2H)-one")
