214491-07-3

Usage

Uses

Used in Pharmaceutical Industry:
Kotalanol is used as an antidiabetic agent for its potent inhibitory activity against sucrase, which helps in managing blood sugar levels and improving the overall metabolic health of individuals with diabetes.
Used in Drug Development:
Kotalanol is used as a key component in the development of new drugs targeting diabetes and related metabolic disorders due to its effectiveness in inhibiting α-glucosidase, a crucial enzyme involved in carbohydrate metabolism.
Used in Research and Development:
Kotalanol serves as an important compound in research and development for understanding the mechanisms of diabetes and the potential of natural products in the treatment and management of the disease. Its potent inhibitory activity against sucrase makes it a valuable tool for studying the enzyme's role in carbohydrate metabolism and the development of novel therapeutic strategies.

Upstream product

• 1228577-25-0 3,6-O-isopropylidene-1,2,4-tri-O-methoxymethyl-D-glycero-D-galacto-heptitol-5,7-cyclic sulfate 
• 635316-05-1 (2R,3S,4S)-3,4-bis((4-methoxybenzyl)oxy)-2-(((4-methoxybenzyl)oxy)methyl)tetrahydrothiophene 
• 1228577-27-2 C₄₅H₆₄O₁₈S₂ 
• 1143516-41-9 2,3,5-tri-O-p-methoxybenzyl-1,4-dideoxy-1,4-[[2S,3S,4R,5R,6S]-5,7-benzylidene-2,4,6-tri-O-p-methoxybenzyl-3-(sulfooxy)heptyl]-(R)-epi-sulfoniumyIidine-D-arabinitol 
• 1187860-97-4 2,3,5-tri-O-p-methoxybenzyl-1,4-dideoxy-1,4-[(2S,3S,4R,5R,6S)-5,7-benzylidene-2,4,6-tri-O-p-methoxybenzyl-3-(sulfooxy)heptyl]-(R)-epi-sulfoniumylidine-D-arabinitol inner salt 

Relevant academic research and scientific papers

SALACINOL AND PONKORANOL HOMOLOGUES, DERIVATIVES THEREOF, AND METHODS OF SYNTHESIZING SAME

Salacinol and ponkoranol homologues, derivatives thereof and methods of synthesizing and using said homologies and derivatives. The derivatives include stereoisomers, de-O-sulfonated compounds and congeners of the naturally occurring homologues. Some of the derivatives exhibit enhanced glucosidase inhibitory bioactivity in comparison to the naturally occurring compounds which have been isolated from salacia reticulata.

Synthesis of a biologically active isomer of kotalanol, a naturally occurring glucosidase inhibitor

The syntheses of an isomer of kotalanol, a naturally occurring glucosidase inhibitor, and of kotalanol itself are described. The target compounds were synthesized by nucleophilic attack of PMB-protected 1,4-anhydro-4-thio-d-arabinitol at the least hindered carbon atom of two 1,3-cyclic sulfates, which were synthesized from d-mannose. Methoxymethyl ether and isopropylidene were chosen as protecting groups. The latter group was critical to ensure the facile deprotection of the coupled products in a one-step sequence to yield kotalanol and its isomer. The stereoisomer of kotalanol, with the opposite stereochemistry at the C-6′ stereogenic centre, inhibited the N-terminal catalytic domain of intestinal human maltase glucoamylase (ntMGAM) with a Ki value of 0.20 ± 0.02 μM; this compares to a Ki value for kotalanol of 0.19 ± 0.03 μM. The results indicate that the configuration at C-6′ is inconsequential for inhibitory activity against this enzyme.

METHODS FOR SYNTHESIZING KOTALANOL AND STEREOISOMERS AND ANALOGUES THEREOF, AND NOVEL COMPOUNDS PRODUCED THEREBY

Compounds having the general formula (I): wherein X is S, Se or NH, and stereoisomers thereof, and de-O-sulfonated analogues of all of the foregoing, but excluding naturally occurring kotalanol and de-O-sulfonated kotalanol, and methods for synthesizing same. The compounds are useful as glycosidase inhibitors, and may be used in the treatment of diabetes. The synthetic compounds may also be used as standards in the calibration or grading of natural or herbal remedies produced from natural sources of glycosidase inhibitors such as kotalanol.

Structure proof and synthesis of kotalanol and de-O-sulfonated kotalanol, glycosidase inhibitors isolated from an herbal remedy for the treatment of type-2 diabetes

Kotalanol and de-O-sulfonated-kotalanol are the most active principles in the aqueous extracts of Salacia reticulata which are traditionally used in India, Sri Lanka, and Thailand for the treatment of diabetes. We report here the exact stereochemical structures of these two compounds by synthesis and comparison of their physical data to those of the corresponding natural compounds. The candidate structures were based on our recent report on the synthesis of analogues and also the structure-activity relationship studies of lower homologues. The initial synthetic strategyrelied on the selective nucleophilic attack of p-methoxybenzyl (PMB)-pr otected 4-thio-D-arabinitol at the least hindered carbon atom of two different, selectively protected 1,3-cyclic sulfates to afford the sulfonium sulfates. The protecting groups consisted of a methylene acetal, in the form of a seven-membered ring, and benzyl ethers. Deprotection of the adducts yielded the sulfonium ions but also resulted in de-O-sulfonation. Comparison of the physical data of the two adducts to those reported for de-O-sulfonated natural kotalanol yielded the elusive structure of kotalanol by inference. The side chain of this compound was determined to be another naturally occurring heptitol, D-perseitol (D-glycero-D-galacto-heptitol) with a sulfonyloxy group at the C-5 position. The synthesis of kotalanol itself was then achieved by coupling PMB-protected 4-thio-D-arabinitol with a cyclic sulfate that was synthesized from the naturally occurring D-perseitol. The work establishes unambiguously the structures of two natural products, namely, kotalanol and de-O-sulfonated kotalanol.