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The synthesis and structure-activity relationship (SAR) of thiophene-C-glucosides have been explored, and the human sodium-dependent glucose cotransporter 2 (hSGLT2) inhibitory activities and rat urinary glucose excretion (UGE) effects of 3a-f were evaluated. As a result, they showed good hSGLT2 inhibitory activities and rat UGE effects. In particular, the chlorothiophene derivative 3f showed remarkable inhibitory activity against hSGLT2.

Plasma glucose is continuously filtered through the glomerulus and then is reabsorbed via the transcellular transport system of proximal tubules in the kidney. The glucose reabsorption system in the kidney is mediated by sodium-dependent glucose cotransporters (SGLTs). Most of filtered glucose is reabsorbed by the low affinity, high capacity SGLT2 located in the proximal renal tubule. SGLT2 inhibitors, such as T-1095, enhance urinary glucose excretion and consequently lower blood glucose levels independent of insulin action. The principle behind SGLT inhibition involves the amelioration of diabetic conditions without increasing body weight and the risk of hypoglycemia. A number of SGLT2 inhibitors are being developed for the treatment of diabetes. This review offers the summary of structure-activity relationships (SARs) and pharmacological profiles of T-1095 and diverse SGLT2 inhibitors.

The seven-membered S- and Y-ring systems of maitotoxin (1) were stereoselectively synthesized based on the rearrangement-ring expansion of the six-membered ethers having the mesylate group on the α-side chain.

The 7, 7-membered CD ring system of hemibrevetoxin B was stereoselectively synthesized. The crucial steps involve the Sharpless asymmetric epoxidation, cyclization to the 6-membered ether, and double rearrangement of the 6, 6-membered bicyclic ether with the simultaneous ring expansion.

Six- and seven-membered ether rings were stereoselectively synthesized based on the rearrangement of the cyclic ether with the simultaneous ring expansion. Treatment of ether having a mesylate or bromide group as the leaving group on the side chain with Zn(OAc)2 or AgOAc stereoselectively produced the ring expanded ether in good yield.

The seven-membered S- and Y-ring systems of maitotoxin (1) were stereoselectively synthesized based on the rearrangement-ring expansion of the six-membered ethers having the mesylate group on the α-side chain.