Synthesis Of Bis-glycosylguanidino-Benzene And Cyclizing Products Of Glycosylamidothioureas

Substituted guanidines are found in many compounds of medicinal interest. For example, they have shown a strong antihypertensive effect, decline blood sugar and antimicrobial activity; some containing thiazole have been reported to show antitubercular, antimalarial. Recently, guanidine-containing sugar have attracted the attention of pharmaceutical industry, guanidine-containing sugar have exhibited anti-influenza and anti-HIV. In order to broaden the synthesis and activity research of glycosylguanidine, we have synthesized a series of new glycosylguanidine compounds, containing bisglycosyl, bisbenzothiazolyl and bisguanidyl.1,3,4-Oxadiazoles are broadly used as herbicides, growth hormone, bactericides, effective insecticides and antiphlogistic. The sulfonamide group R1SO2–NHR2 is a common pharmacophore found in various biologically active molecules, enzyme inhibitors and receptor antagonists. The introduction of sugar core into medicine can lower the toxicity and make the medicine, containing sugar core, more biodegradable in body. Therefore, we expect to realize reinforcement of physiological activities by means of combining the glycosyl and sulfonamide with 1,3,4-oxadiazoles.The structure of All compounds synthesized was conformed by data of 1H NMR, IR, MS (ESI), and elemental analysis.The mainly works in this paper:1. The O-protected glycosyl isothiocyanate was refluxed with 1,4-diaminobenzene in CHCl3 to give 1,4-bis(N-glycosyl)thioureylenebenzene. Then 1,4-bis[N-(4/6-substituted benzothiazole-2-yl)-N′-glycosylguanidino]benzenes were obtained by reaction of 1,4-bis(N-glycosyl)thioureylenebenzene with 2-amino-4/6-benzothiazoles and HgCl2 in the present of TEA in DMF.2. N-glycosyl-N′-amidothioureas were synthesized by the reaction of N-p- toluenesulfonyl-L-α-amino acid hydrazides with glycosyl isothiocyanates. Then the N-glycosyl-N′-amidothio- ureas were cyclized under the system of Hg(OAc)2/EtOH to afford a series of new compounds, 2- p-toluenesulfonylaminoalkyl-5-glycosylamino-1,3,4-oxadiazoles.The innovations of the thesis are based on the follows:1. The reaction of glycosyl isothiocyanates with 1, 4-diaminobenzene give rise to 3 novel 1, 4-bis(N-glycosyl)thioureylenebenzenes. 15 novel 1,4-bis[N-(4/6-substituted benzothiazole-2-yl)-N′-glycosylguanidino]benzenes were obtained by reaction of 1, 4-bis(N-glycosyl)thioureylenebenzenes with 2-amino-4/6-benzothizoles. 2. 9 novel N-glycosyl-N′-amidothioureas were synthesized. 9 novel 1, 3, 4-Oxadiazole derivatives containing glycosyl and sulfonamido, which were unreported in the literatures, were obtained by cyclization of the N-glycosyl-N′-amidothioureas.