Synthesis Of Phlorizin Analogues And 1-Deoxynojirimycin(DNJ)

Phlorizin was firstly isolated from the bark of the apple tree. Phlorizin’s principal pharmacological action is to produce renal glycosuria and block glucose absorption through inhibition of the sodium-glucose co-transporters (SGLTs) located in the proximal renal tubule and mucosa of the small intestine.There are two important SGLT isoforms, SGLT1 and SGLT2. SGLT1 is located primarily in small intestinal cells. Besides, it is also present in the kidney and the heart. SGLT2 is located exclusively in the early proximal convoluted tubule (SI segment). Ninety percent of filtered glucose is reabsorbed by SGLT2; the other 10% is reabsorbed by SGLT1 in the late proximal straight tubule (S3 segment).Therefore, blocking the function of SGLT2 selectively would inhibit the reabsorbtion of glucose in the kidney and the glucose is excreted in the urine. Because of this, blood sugar is lowered. SGLT2 inhibitors are the most likely to cure type 2 diabetes mellitus (T2DM).The clinical applicability of phlorizin is limited by poor oral bioavailability, lack of selectivity for SGLT2 and susceptibility to glucosidase degradation with oral administration. Phlorizin also inhibits SGLT1, which has the potential to cause significant side effects in the gastrointestinal tract. At present, a number of SGLT2 inhibitors (phlorizin analogues) are under development.1-Deoxynojirimycin (DNJ) principally exists in the mulberry leaves and is a kind of antidiabetic agents with no harm. As a kind of strong inhibitor of a-glucosidase, DNJ has demonstrated interesting antidiabetic, antiviral, antimetastatic properties, and so on. The content of DNJ in nature is very low which results in being isolated hardly. The DNJ’s structure of chiral centers brings the challenge regarding to its synthesis.This study consists of two parts. In the first part, the phlorizin analogues were synthetized via click reaction between the substituted benzyl azides and alkynyl propyl products based on cheap glucose. All phlorizin analogues have not been reported in the papers. In the second part, DNJ was successfully synthesized based on methyl-a-D-glucopyranoside via oxidation, ammoniation open-loop, reductive amination et al. The products were characterized by’H-NMR, 13C-NMR, MS et al.