Uses of Acetobromo-α-D-glucuronic acid methyl ester

The IUPAC name of acetobromo-α-D-glucuronic acid methyl ester (C13H17BrO9) is methyl (2S,3S,4S,5R,6R)-3,4,5-triacetyloxy-6-bromooxane-2-carboxylate, with the CAS registry number 21085-72-3.

Acetobromo-α-D-glucuronic acid methyl ester is a white crystalline solid.

Due to the minimized cell entry of glucuronides, which affords a high ratio between the toxicity-related IC50 for the prodrug and the drug, and advantageous in that these typically afford a significantly enhanced aqueous solubility, a feature of high importance for hydrophobic drugs, acetobromo-α-D-glucuronic acid methyl ester is usually used for the synthesis of some non-toxic glucuronide prodrugs to improve some performance of drugs and drug delivery¹. Some examples are as follows:

Acetobromo-α-D-glucuronic acid methyl ester is used for the synthesis of HMR1098-S-glucuronide methyl ester, a new K-ATP-blocking agent being developed as a drug for prevention of sudden cardiac death.

Acetobromo-α-D-glucuronic acid methyl ester is used for the synthesis of water-soluble glucuronide derivatives of Camptothecin, which is used for cancer prodrug monotherapy and antibody-directed enzyme prodrug therapy (ADEPT)².

Acetobromo-α-D-glucuronic acid methyl ester is used for the synthesis of glucuronide prodrug compounds of Janus kinase (JAK) inhibitor tofacitinib, which could be cleaved by β-glucuronidase enzymes such as those produced by the microbiome in the gastrointestinal tract, thereby increasing levels of tofacitinib at the site of gastrointestinal inflammation and limiting the systemic exposure of tofacitinib when treating localized inflammatory diseases³.

Phosphorodiamidic mustards, such as cyclophosphamide and ifosfamide, are structurally-related anticancer agents that exhibit broad spectrum clinical efficacy. However, these compounds give rise to toxic byproducts that limit their therapeutic efficacy. Acetobromo-α-D-glucuronic acid methyl ester is used for the synthesis of glucuronate prodrug of phosphorodiamidic mustard. Using this approach, phosphoramide mustards can be delivered into cells to avoid toxicologic problems⁴.

Acetobromo-α-D-glucuronic acid methyl ester is used for the synthesis of curcumin β-D-glucuronide (curcumin monoglucuronide, CMG), which could be used as an anticancer agent without the serious side effects that most anticancer agents have⁵.

When you are using this chemical, please be cautious about it as the following:

Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust.

References

1.Walther, R.; Jarlstad Olesen, M. T.; Zelikin, A. N., Extended scaffold glucuronides: en route to the universal synthesis of O-aryl glucuronide prodrugs. Organic & biomolecular chemistry 2019, 17 (29), 6970-6974.
2.Leu, Y.-L.; Roffler, S. R.; Chern, J.-W., Design and Synthesis of Water-Soluble Glucuronide Derivatives of Camptothecin for Cancer Prodrug Monotherapy and Antibody-Directed Enzyme Prodrug Therapy (ADEPT). Journal of Medicinal Chemistry 1999, 42 (18), 3623-3628.
3.Long, D. D.; Wilton, D. A. A.; Loo, M. M. Glucuronide prodrugs of tofacitinib. 2018.
4.Ghosh, A. K.; Farquhar, D., A methyl glucuronate prodrug of phosphorodiamidic mustard. Tetrahedron Lett 1997, 38 (51), 8795-8798.
5.Ozawa, H.; Imaizumi, A.; Sumi, Y.; Hashimoto, T.; Kanai, M.; Makino, Y.; Tsuda, T.; Takahashi, N.; Kakeya, H., Curcumin beta-D-glucuronide plays an important role to keep high levels of free-form curcumin in the blood. Biological & Pharmaceutical Bulletin 2017, 40 (9), 1515-1524