TY - DATA T1 - 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 PY - 2009/04/22 AU - Kumarasamy Jayakanthan AU - Sankar Mohan AU - B. Mario Pinto UR - https://acs.figshare.com/articles/journal_contribution/Structure_Proof_and_Synthesis_of_Kotalanol_and_De_i_O_i_sulfonated_Kotalanol_Glycosidase_Inhibitors_Isolated_from_an_Herbal_Remedy_for_the_Treatment_of_Type_2_Diabetes/2862355 DO - 10.1021/ja900867q.s001 L4 - https://ndownloader.figshare.com/files/4560181 KW - nucleophilic attack KW - benzyl ethers KW - sulfonium ions KW - Kotalanol KW - compound KW - stereochemical structures KW - carbon atom KW - side chain KW - Structure Proof KW - Glycosidase Inhibitors KW - adduct KW - PMB KW - synthesis KW - candidate structures KW - kotalanol KW - cyclic sulfate KW - Herbal Remedy KW - sulfonyloxy group KW - methylene acetal KW - sulfonium sulfates KW - data KW - Salacia reticulata KW - Sri Lanka N2 - 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 strategy relied on the selective nucleophilic attack of p-methoxybenzyl (PMB)-protected 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. ER -