Product name: 6''-O-Malonyldaidzin
Synonym name: Malonyldaidzin;Daidzin 6''-O-malonate
Catalogue No.: BP4547
Cas No.: 124590-31-4
Formula: C₂₄H₂₂O₁₂
Mol Weight: 502.428
Botanical Source:
Type of Compound: Isoflavones

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

The product could be supplied from milligrams to grams
Inquire for bulk scale.

For Reference Standard and R&D, Not for Human Use Directly.

NMR of 6''-O-Malonyldaidzin

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Isoflavones, as a class of secondary metabolites widely present in leguminous plants, have attracted much attention due to their diverse biological activities. Among them, soy isoflavones and their derivatives have shown great potential in preventing and improving chronic diseases, especially those related to hormone metabolism. 6 '' - O-Malonyldaidzin (CAS: 124590-31-4) is a malonylated derivative of daidzin and one of the main naturally occurring forms of isoflavone glycosides in soybeans and their products. Compared to its deacetylated product Daidzein or glycosidic daidzein, 6 '' - O-malonyldaidzein is more abundant in plants, but its physicochemical properties are unstable and prone to de esterification or glycoside hydrolysis during processing, storage, or in vivo metabolism, which poses certain challenges for its research. In recent years, with the advancement of analytical techniques and the deepening of pharmacological research, the unique estrogenic regulatory activity of this compound and its potential application value in osteoporosis, menopausal syndrome, cardiovascular disease, and cancer prevention have gradually been revealed. This article aims to systematically review the chemical structure, plant origin, pharmacological activity, mechanism of action, pharmacological evaluation, and clinical application prospects of 6 '' - O-propanediol daidzein, in order to provide comprehensive scientific references for the in-depth research and development of this natural product.

Chemical structure and physicochemical properties

The chemical name of 6 '' - O-propanediol daidzein is 7-hydroxy-3- (4-hydroxyphenyl) -4H-1-benzopyran-4-one 7-O - β - D-glucopyranosyl-6 '' - O-propanedioate. Its molecular formula is C24H22O12 and its molecular weight is 502.4280. Structurally, its parent nucleus is daidzein (7,4 '- dihydroxyisoflavone), which is connected to a β - D-glucosyl group via an O-glycosidic bond on the C-7 hydroxyl group. The 6 '' - hydroxyl group of the glucose group further undergoes esterification reaction with malonic acid to form a malonyl group (- O-CO-CH2-COO -), which is the key structural feature that distinguishes it from daidzin and acetylated daidzin.

This unique malonylation modification profoundly affects its physicochemical properties. Firstly, the introduction of malonyl groups significantly increases the polarity and water solubility of the molecule. Its topological polar surface area (TPSA) is as high as 193.19 Å ², the calculated LogP value is only 0.2905, and the predicted water solubility is 1.6410 mg/mL, indicating its good hydrophilicity, which is consistent with its storage form in plant cell vacuoles. However, the malonyl bond is highly sensitive to heat, acid, base, and enzymes such as β - glucosidase and esterase. During heating, fermentation, or gastrointestinal digestion, this compound is highly susceptible to deprotonation to produce daidzein, or further hydrolysis to produce daidzein. This instability is a key consideration factor in the fluctuation of its content in processed foods and in the study of its bioavailability in vivo. In addition, based on its molecular weight and polarity parameters, its ability to penetrate the blood-brain barrier is predicted to be low, suggesting that the direct action of the central nervous system may be limited. The preliminary in vitro safety assessment shows that the hERG channel inhibition risk is negative, and the Ames test result is 0.6 (usually considered negative if it is less than 2), indicating that its potential mutagenic risk is low and has a safety basis for further development.

Plant sources and extraction methods

6 '' - O-propanediol daidzein is mainly found in leguminous plants, especially in soybean (Glycine max) seeds where it is most abundant. It is the main storage form of natural isoflavones in soybeans, and its content is usually much higher than its corresponding non acylated glycosides (such as daidzein) and aglycones (daidzein). There are significant differences in the content of soybean among different varieties, tissue parts, and growth stages. In addition, other traditional medicinal plants such as Pueraria lobata also contain a certain amount of malonylated isoflavone glycosides.

Due to the instability of 6 '' - O-malonyldaidzein to thermal and chemical environments, mild conditions are required for its extraction, separation, and purification to avoid degradation. The conventional extraction methods include:
1. Solvent extraction method The most commonly used method is to use a 70% -80% methanol or ethanol aqueous solution for extraction or ultrasound assisted extraction at room temperature or lower temperatures (such as 4 ° C). High concentration organic solvents can effectively precipitate proteins while maximizing the extraction of polar isoflavone glycosides. Acidic solvents (such as those containing small amounts of acetic acid) are sometimes used to inhibit the oxidation of phenolic substances, but the pH needs to be strictly controlled to avoid hydrolysis of malonyl groups.
2. Solid phase extraction (SPE)The crude extract is often subjected to preliminary enrichment, desalination, and decolorization using a C18 solid-phase extraction column. Different ratios of methanol water gradient elution are used to preliminarily separate isoflavone components of different polarities.
3. Chromatographic separation technology Further purification relies on preparative high-performance liquid chromatography (HPLC). Usually, a reverse phase C18 chromatography column is used, with acetonitrile water system containing low concentrations of formic acid or acetic acid as the mobile phase for gradient elution. Operating at low temperatures and processing samples as soon as possible is key to maintaining compound integrity. In recent years, liquid-liquid distribution chromatography techniques such as high-speed countercurrent chromatography (HSCCC) have also been used to prepare high-purity malonylated isoflavones due to their advantages of avoiding irreversible adsorption and high recovery rate.
4. Identification Method: The structural identification of this compound mainly depends on the UV spectrum (UV, characteristic absorption of isoflavones), mass spectrometry (MS, especially the electrospray ionization mass spectrometry ESI-MS can provide molecular ion peaks and characteristic fragment ions, such as fragments that lose malonyl and glucose groups), and nuclear magnetic resonance (NMR, especially 1H NMR and 13C NMR, can accurately assign protons and carbon signals on sugar and malonyl groups).

Pharmacological activity research

A large number of in vitro and partially in vivo studies have shown that 6 '' - O-malonyldaidzein exhibits various pharmacological activities through its prototype or metabolites, with the core revolving around its estrogenic/regulatory effects.

1. Estrogen like and selective estrogen receptor modulation (SERM) activity 6 '' - O-propanediol daidzein itself and its metabolite daidzein can bind to estrogen receptors (ER α and ER β), but its binding affinity is much lower than that of endogenous estrogen estradiol. It is worth noting that they exhibit relatively higher selectivity towards ER β. This selective binding property enables it to simulate the beneficial effects of estrogen in certain tissues such as bone and cardiovascular system, while in tissues such as breast and endometrium, it may produce anti estrogen effects or weak effects, thereby exerting functions similar to selective estrogen receptor modulators (SERMs). Animal experiments have shown that soybean extract rich in malonyl isoflavones can effectively prevent bone density decline in ovariectomized rats, improve blood lipid abnormalities and endothelial function in menopausal model animals.
2. Regulation of hormone related enzyme systems：
   • Aromatase (CYP19A1) inhibition Research has shown that daidzein and its related compounds can mildly inhibit aromatase activity, which is responsible for converting androgens into estrogens. This inhibition may have a regulatory effect on the pathological environment of estrogen dependent diseases.
   • Regulation of sex hormone binding globulin (SHBG)Isoflavones may upregulate the synthesis of SHBG in the liver. Elevated levels of SHBG can reduce the concentration of free sex hormones in the blood, indirectly regulating the bioavailability of hormones.
3. The impact on the hypothalamic pituitary gonadal axis There are studies suggesting that isoflavones may play a subtle regulatory role in reproductive endocrine by affecting the secretion of follicle stimulating hormone (FSH) and luteinizing hormone (LH), but the specific mechanism and direct contribution of 6 '' - O-malonyldaidzein still need to be clarified.
4. Antioxidant and anti-inflammatory activities As a phenolic compound, 6 '' - O-malonyldaidzein has a certain ability to scavenge free radicals and can inhibit the expression of inflammatory factors (such as TNF - α, IL-6) by regulating signaling pathways such as NF - κ B and MAPK, which is related to its cardiovascular protection and potential anti-cancer adjuvant effects.
5. Other potential activities Preliminary studies also suggest that it may be beneficial in improving insulin resistance, protecting nerves, and other aspects, but these activities are mostly related to its metabolites daidzein or intestinal metabolite estrol.

Mechanism of action and molecular targets

The pharmacological effects of 6 '' - O-malonyldaidzein are mainly mediated by its metabolites, but its prototype may also be involved in some direct effects. Its core mechanism involves the coordinated regulation of multiple targets and pathways.

1. Classical genomic pathway (nuclear receptor pathway)Metabolite daidzein acts as a ligand and binds to estrogen receptors ER α (ESR1) and ER β (ESR2) in the nucleus. Compared with estradiol, its affinity for ER β is relatively high. After dimerization of ligand receptor complexes, they bind to estrogen response elements (ERE) in the promoter region of target genes, recruiting co activators or co repressors to regulate transcription of specific genes. For example, in osteoblasts, upregulation of osteogenic related genes (such as collagen and alkaline phosphatase) through this pathway promotes bone formation; Upregulation of nitric oxide synthase (eNOS) expression in endothelial cells promotes vasodilation.
2. Non genomic pathway (membrane initiation signaling pathway)Isoflavones and their derivatives can also bind to membrane associated estrogen receptors (such as GPER1) or rapidly activate the intracellular second messenger system through other membrane receptors, such as activating the PI3K/Akt and MAPK/ERK signaling pathways. The activation of these pathways occurs within minutes to hours, mediating the rapid vasodilation effect of estrogen, cell survival signaling, and cross talk with other growth factor signaling.
3. Key molecular target interaction network：
   • Estrogen receptors (ESR1/ESR2)Core target, mediating most estrogen like effects.
   • Androgen receptor (AR)Daidzein can serve as a weak antagonist of AR and may have positive implications for prostate diseases.
   • Progesterone receptor (PGR)May affect progesterone signaling through ER mediated indirect pathways or cross talk.
   • Aromatase (CYP19A1)Inhibit enzyme activity and reduce local estrogen synthesis.
   • Sex hormone binding globulin (SHBG)By affecting its synthesis, regulate the levels of free hormones in the blood.
   • Gonadotropin receptor (FSH/LHB)May affect the secretion of pituitary hormones through feedback regulation.
4. Epigenetic regulation Recent studies have found that isoflavones can also regulate gene expression in the long term by affecting epigenetic modifications such as histone acetylation and DNA methylation, which may be one of the mechanisms underlying their cancer chemopreventive effects.

Evaluation of drug properties and pharmacokinetics

As a natural product, the drug like and pharmacokinetic (PK) properties of 6 '' - O-malonyldaidzein are key factors in evaluating its development potential.

1. absorb Due to its strong hydrophilicity and large molecular weight, the passive transmembrane absorption of intact 6 '' - O-propanedioyl daidzein in the intestine is poor. After oral administration, it is mainly metabolized in the upper small intestine and large intestine through the action of gut microbiota and brush border enzymes in intestinal mucosal cells. Firstly, malonyl groups are easily hydrolyzed by esterases to produce daidzein; Subsequently, daidzein hydrolyzes the glucose group under the action of β - glucosidase, releasing the aglycone daidzein. Daidzein is the main absorbed form, with high lipid solubility, and can enter intestinal epithelial cells through passive diffusion.
2. distribution After absorption, daidzein undergoes phase II metabolism (glucuronidation and sulfation) in the liver, forming more water-soluble complexes that enter the bloodstream. Therefore, plasma mainly exists in the form of bound metabolites. Due to the polarity of their prototypes and aglycones, they are distributed to most tissues, but as mentioned earlier, their ability to penetrate the blood-brain barrier is limited.
3. Metabolism The liver is the main site of metabolism, involving binding reactions of enzyme systems such as UGT and SULT. In addition, gut microbiota metabolism is crucial. The gut microbiota of some individuals (approximately 30-50% of Asians) can further convert daidzein into the more active estrogen (S-Equol), which has a higher affinity for ER β and stronger antioxidant activity, and is considered a key contributor to many health effects of isoflavones. Individual microbiota differences lead to significant individual variations in the biological effects of isoflavones.
4. excretion Isoflavones and their metabolites are mainly excreted through the kidneys with urine, and some enter the enterohepatic circulation through bile.
5. Challenges and Strategies in Drug Development：
   • challenge The oral bioavailability of the prototype compound is extremely low; The in vivo effects mainly rely on unstable intestinal metabolites, with significant individual differences; Strong water solubility but poor chemical stability.
   • Strategy：
     • Prodrug design Improve its stability or alter metabolic pathways through chemical modification, such as developing more stable malonyl analogues or preparing phospholipid complexes or cyclodextrin inclusion complexes to enhance absorption and stability.
     • Formulation technology Using microencapsulation, nanoemulsion, solid dispersion and other formulation technologies to protect it from premature degradation by gastric acid and upper gastrointestinal enzymes, achieving colon targeted delivery and releasing active ingredients under the action of colon microbiota.
     • Joint probiotics: Used in combination with specific probiotics that can produce β - glucosidase and estradiol, such as lactobacilli and bifidobacteria, to improve their biotransformation efficiency and consistency of effects.

Clinical application prospects and prospects

Based on its extensive pharmacological activity and good safety foundation, 6 '' - O-propanediol daidzein and its natural extracts rich in it have potential application value in multiple fields.

1. Alternative therapies for menopausal syndrome: As a phytoestrogen, it can be used to alleviate the vasomotor symptoms such as hot flashes, night sweats, heart palpitations, and may have a lower risk of breast cancer and endometrial cancer than traditional hormone replacement therapy (HRT). One of the research directions is to develop standardized extracts rich in malonyl isoflavones.
2. Prevention and Adjuvant Treatment of Osteoporosis Through its selective estrogen like effect, it inhibits osteoclast activity and promotes osteoblast function, helping to maintain bone density in postmenopausal women and reduce the risk of fractures.
3. Cardiovascular Health: It can prevent atherosclerosis by improving blood lipid profile (reducing LDL-C, increasing HDL-C), enhancing vascular endothelial function, anti-oxidation and anti-inflammatory.
4. Cancer chemoprevention: Especially for hormone related cancers (such as breast cancer and prostate cancer), it may play a preventive role through a variety of mechanisms (anti proliferation, apoptosis promotion, anti angiogenesis, hormone regulation). However, its role in cancer patients is controversial and requires careful evaluation.
5. Other fields It also has research and exploration in improving skin aging (promoting collagen synthesis) and assisting in the management of type 2 diabetes.

Future prospects and research directions：
1. In depth mechanism research More research is needed to clarify whether the prototype of 6 '' - O-propanedioyl daidzein has unique biological activity independent of its hydrolysis products and its direct molecular targets.
2. Individualized nutrition and healthcare Strengthen research on the phenotypic differences between "estradiol producers" and "non producers", and develop personalized supplementation recommendations based on gut microbiota testing to improve intervention effectiveness.
3. Innovative drug delivery system As mentioned earlier, developing novel delivery systems to improve their stability, targeting, and bioavailability is key to transforming them from dietary components into drugs.
4. High quality clinical evidence Currently, most of the evidence comes from epidemiological observations, in vitro and animal experiments. It is urgent to design rigorous, large-scale, and long-term randomized controlled clinical trials (RCTs) to confirm their preventive and therapeutic effects on specific diseases, and to clarify the optimal dosage and medication cycle.
5. Re evaluation of safety Although overall safe, attention should still be paid to the potential effects on thyroid function and reproductive system development (especially during perinatal exposure) under high-dose, long-term use.

Conclusion

6 '' - O-propanediol daidzein, as a rich but unique natural isoflavone glycoside in soybeans, is one of the key chemical entities connecting soybean dietary consumption with various health benefits. It exerts a comprehensive pharmacological effect of multi-target estrogen regulation, antioxidant, anti-inflammatory, etc. through complex metabolic transformation, mainly in the form of its aglycone daidzein and secondary metabolite estrone, showing broad prospects in improving menopausal symptoms, maintaining bone and cardiovascular health, and preventing chronic diseases. However, its inherent chemical instability, low oral bioavailability, and significant individual metabolic differences are the main challenges that constrain its transition from "dietary components" to "standardized drugs". Future research should focus on revealing its prototype activity, innovating delivery strategies, elucidating the mechanisms of individual response differences, and verifying its efficacy and safety through solid clinical studies. With the deepening of precision nutrition and natural product drug development, 6 '' - O-propanediol daidzein is expected to play a more important role in the fields of preventive medicine and alternative therapies.