5-O-(beta-Hydroxyethyl)diosmin
[CAS# 115960-14-0]

Identification

• Classification: API >> Blood system medication >> Platelet proliferative drug
• Name: 5-O-(beta-Hydroxyethyl)diosmin
• Synonyms: Hidrosmin; 5-(2-hydroxyethoxy)-2-(3-hydroxy-4-methoxyphenyl)-7-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-[[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxymethyl]oxan-2-yl]oxychromen-4-one
• Molecular Formula: C₃₀H₃₆O₁₆
• Molecular Weight: 652.60
• CAS Registry Number: 115960-14-0
• SMILES: C[C@H]1[C@@H]([C@H]([C@H]([C@@H](O1)OC[C@@H]2[C@H]([C@@H]([C@H]([C@@H](O2)OC3=CC4=C(C(=C3)OCCO)C(=O)C=C(O4)C5=CC(=C(C=C5)OC)O)O)O)O)O)O)O

Properties

• Solubility: Practically insoluble (0.044 g/L) (25 °C), Calc.^*
• Density: 1.63±0.1 g/cm³ (20 °C 760 Torr), Calc.^*
• Boiling point: 962.7±65.0 °C 760 mmHg (Calc.)^*
• Flash point: 311.1±27.8 °C (Calc.)^*
• Index of refraction: 1.689 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Discovery and Applications

5-O-(beta-Hydroxyethyl)diosmin is a semi-synthetic flavonoid derivative obtained from diosmin, a naturally occurring flavone glycoside primarily found in citrus species. Chemically, it is characterized by the addition of a hydroxyethyl group at the 5-O position of diosmin, a modification designed to enhance water solubility and improve pharmacokinetic properties compared to the parent compound. This structural modification allows better absorption and distribution, addressing the limited bioavailability often associated with natural flavonoids.

The discovery of 5-O-(beta-Hydroxyethyl)diosmin arose from efforts to develop more effective and bioavailable flavonoid derivatives for vascular and circulatory health. Diosmin itself has been traditionally used for its venotonic, vasoprotective, and anti-inflammatory effects, and the hydroxyethyl modification was introduced to optimize these therapeutic benefits while improving its pharmacological profile.

Pharmacologically, 5-O-(beta-Hydroxyethyl)diosmin retains and often enhances the biological activities of diosmin. It exhibits potent venotonic effects, promoting venous tone and reducing venous capacitance, which is particularly beneficial in chronic venous insufficiency and varicose vein conditions. The compound also demonstrates capillary-protective activity, reducing capillary permeability and fragility, which can mitigate edema and bruising associated with vascular insufficiencies.

In addition to vascular benefits, 5-O-(beta-Hydroxyethyl)diosmin shows anti-inflammatory properties by modulating pathways involved in leukocyte adhesion, cytokine production, and oxidative stress. This contributes to its efficacy in conditions such as hemorrhoidal disease, where inflammation and microcirculatory disturbances are prominent. The compound also exhibits antioxidant activity, scavenging reactive oxygen species and protecting endothelial cells from oxidative damage, which supports long-term vascular health.

Pharmacokinetic studies indicate that the hydroxyethyl modification enhances solubility and absorption, allowing the compound to achieve more consistent plasma levels compared to unmodified diosmin. This improved bioavailability facilitates its oral administration and therapeutic efficacy, making it suitable for use in dietary supplements and pharmaceutical formulations targeting venous and microcirculatory disorders.

Clinically, 5-O-(beta-Hydroxyethyl)diosmin has been employed as a venotonic agent and in combination with other flavonoids for the management of chronic venous insufficiency, hemorrhoids, and related vascular conditions. Its safety profile is favorable, with low toxicity and minimal adverse effects reported in preclinical and clinical evaluations. The compound is well tolerated in long-term use, making it suitable for chronic therapeutic regimens.

Overall, 5-O-(beta-Hydroxyethyl)diosmin is a semi-synthetic flavonoid derivative with enhanced pharmacokinetic and pharmacodynamic properties compared to diosmin. Its venotonic, anti-inflammatory, capillary-protective, and antioxidant activities make it a valuable compound for managing venous disorders and supporting vascular health. Continued research on its mechanism of action, clinical efficacy, and potential applications is likely to expand its role in therapeutic and nutraceutical contexts.

References

2020. Phlebotonics for venous insufficiency. The Cochrane Database of Systematic Reviews, 11(11).
DOI: 10.1002/14651858.cd003229.pub4

2016. Phlebotonics for venous insufficiency. The Cochrane Database of Systematic Reviews, 4.
DOI: 10.1002/14651858.cd003229.pub3

1992. Therapeutic effects of hidrosmin on chronic venous insufficiency of the lower limbs. Current Medical Research and Opinion, 12(8).
DOI: 10.1185/03007999209111529