22457-89-2

crystals

Biotamin,Sankyo

Vitamin B1 analog. Synthetic S-acyl derivative of Thiamine (T344185).

ChEBI: A thioester that is a synthetic analogue of thiamine obtained by acylative cleavage of the thiazole ring and O-phospohorylation.

28.6 g 84% phosphoric acid was heated to temperature about 270°C. After cooling to 100°C 4 g thiamine hydrochloride (vitamin B1 hydrochloride) was added and left at temperature 100°C before an isolation of HCl was ended. After adding of an ice water and acetone, phosphate ester of vitamin B1 was fallen. The precipitate was dissolved in 17 ml 1 N HCl and stood at ambient temperature 7 days for a hydrolysis. Then a solution was with acetone diluted and the mixture was cooled, whereupon vitamin B1 monophosphate hydrochloride was isolated.
The solution of 4.3 parts vitamin B1 monophosphate hydrochloride in 16 parts of water was diluted with 11 parts 15% NaOH, 2.1 parts benzoyl chloride was dropwise added with stirring and cooling. The obtained mixture was neutralized, evaporated in vacuum, acidified with concentrated HCl to pH 3.5- 4, whereupon a crude S-derivative of vitamin B1 monophosphate ester was precipitated. The product was suspended in water, was bringing with NaOH to pH 7 and was acidified to pH 4. 3.4 g refined S-benzoylthiamine Omonophosphate was prepared; MP: 165°C (with decomposition).

Analgesic

S-Benzoylthiamine O-monophosphate (Benfotiamine) is a therapeutic agent. It helps in the prevention of diabetic complications such as, retinopathy, neuropathy and nephropathy. Benfotiamine inhibits the synthesis of glycation end products (AGEs) in diabetes. Benfotiamine is considered as a nutraceutical product for the prevention of diabetic neuropathy.

Benfotiamine was synthesized starting from thiamine chloride hydrochloride via the key intermediate thiamine monophosphate[1]. Crude benfotiamine was purified and crystallized using methanol and sodium dithionite, or recrystallized from various solvents such as methanol and tert-amyl alcohol to yield pure crystalline forms[1].

[1]Hanganu, A., Maximov, M., Maximov, O.-C., Popescu, C. C., Sandu, N., Florea, M., Mirea, A. G., Gârbea, C., Matache, M., & Funeriu, D. P. (2024). Insights into Large-Scale Synthesis of Benfotiamine. Organic Process Research & Development, 28(11), 4069–4078. https://doi.org/10.1021/acs.oprd.4c00351