Mulberry Branch Water Extract Objects In The Inhibition Of ¦Á-glucosidase Activity Of Constituents Of Two Polyhydroxy Piperidine And Pyrrolidine Compounds Of Synthetic Research

The branch of Morus alba L., a Chinese traditional drug, has been used in the treatment of ache and numbness of shoulders, arms and joints. Pharmacological studies reveal that the water extract of the branch has the remarkable activity of a-glucosidase inhibitor in recent years. In order to search for the biologically active principles from the extract, the water extract has been examined by following the activity. By precipitating with alcohol after concentrating the water extract, adsorbing with strongly acidic ion-exchange resin and eluating with 0.5N ammonia solution, the active part was confirmed.Eleven compounds were isolated from the active part by chromatogtaphy on ion-exchange resins or other methods and elucidated structures, including 1-deoxynojirimycin (1), N-methyl-1-deoxynojirimycin(2), fagomine(3), 1,4-dideoxy-1,4-imino-D-arabinitol (5), 2-O-(α-D-galactopyranosyl)-1 -deoxynojiri-mycin (9), 6-O-(β-D-glucopyranosyl)-1-deoxynojirimycin (17), 1,4-dideoxy-1,4-imino-(2-O-β-D-glucopyranosyl)-D-arabinitol (18),γ-aminobutyric acid (22), L-(+) asparaginic acid (23), 4-O-β-D-glucopyranosyl fagomine (24) and pipecolinic acid (25). Pharmacological studies on some compounds revealed that 1-deoxynojirimycin (1), N-methyl-1-deoxynojirimycin (2), fagomine (3) and 1,4-dideoxy-1,4-imino-D-arabinitol (5) are good inhibitors ofα-glucosidase. As the major polyhydroxylated alkaloid in the water extract of the branch (about 0.11% in the drug), and a potent inhibitor of a-glucosidase (IC₅₀<10^-8M), 1-deoxynojirimycin(1) was the principal active compound.In elucidating the structures of 1,4-dideoxy-1,4-imino-D-arabinitol (5) and L-(+) asparaginic acid (23), the reaction of the amino and imino groups with CO₂ was discussed.Three different routes were attempted to obtain the active compound 1,4-dideoxy-1,4-imino-D-arabinitol (5), and the first route starting from L-xylose was completed and optimized, the total yield was 28% and higher than other routes in previous reference. 1,4-Dideoxy-1,4-imino-L-xylitol was also synthesized from D-arabinose by a similar route. On the other hand, the other two routes were delved, and some key reactions were investigated. The generating mechanism of 2,3,5-tri-O-benzyl-Z-xylitol was studied.Starting from five-carbon sugars, the synthesis of the polyhydroxylated piperidine compounds fagomine and 5-epi-fagomine were attempted by cyano substituting and reducting to increase carbon chain. Three methods were used to reduce the cyano, and the method using BH₃·Me₂S was achieved. In order to simplify the reduction condition of the cyano, the protecting groups of the 4- hydroxy of 2, 3, 5-tri-O-benzyl-D-arabinitol were delved.Starting from amino acids, the synthesis methods of N-alkyl and acyl derivatives of polyhydroxylated alkaloids were founded.A total 57 compounds were synthesized, 41 of which are unreported.