Study On The Synthesis Of The Intermediates Of L-borneol 2-O-β-D-apiofuranosyl(1â†'6)-β-D-glucopyranoside Against Myocardial Ischemia In Radix Ophiopogonis

l-Borneol 2-O-β-D-apiofuranosyl(1â†'6)-β-D-glucopyranoside is a kind of characteristic ingredient against myocardial ischemia in Radix Ophiopogonis. Its low content makes it difficult to be extracted. Up to date, there is no report about the synthesis of l-borneol2-O-β-D-apiofuranosyl(1â†'6)-β-D-glucopyranoside. The thesis will explore total synthesis route to obtain l-borneol 2-O-β-D-apiofuranosyl(1â†'6)-β-D-glucopyranoside, aiming at promoting the research on material basis of Radix Ophiopogonis and the study on pharmacological activity of l-borneol 2-O-β-D-apiofuranosyl(1â†'6)-β-D-glucopyranoside. The context is as follows:1. This thesis reviewed the synthesis method of glucosides similar to l-borneol 2-O-β-Dapiofuranosyl(1â†'6)-β-D-glucopyranoside, then designed a route to synthesize l-borneol2-O-β-D-apiofuranosyl(1â†'6)-β-D-glucopyranoside: attaching l-borneol to glucose, then attaching apiose to glucoside.2. To synthesis intermediate p-tolyl 2,3,5-tri-O-acetyl-1-thio-D-apiofuranoside. D-mannose was raw material, through protection by acetone, aldol condensation, selectively deprotection of acetone, reduction by sodium borohydride, oxidation by sodium periodate, gave2,3-O-isopropylidene-D-apiose. Then through acetylation, forming thioglycoside, deprotection of acetone, acetylation again, p-tolyl 2,3,5-tri-O-acetyl-1-thio-D-apiofuranoside was obtained. To increase efficiency and reduce the costing, the paper improved synthesis process on the basis of the traditional method.3. To synthesis the other intermediate l-borneol 2-O-2,3,4-tri-O-acetyl-β-D-glucopyranoside.2,3,4,6-tetra-O-acetyl-β-D-glucose and trichloroacetonitrile reacted to give 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl trichloroacetimidate. l-Borneol and 2,3,4,6-tetra-O-acetyl-β-Dglucopyranosyl trichloroacetimidate reacted to generate l-borneol 2-O-2,3,4,6-tri-O-acetyl-β-D-glucopyranoside through nucleophilic substitution reaction. Then it was deprotected acetyl in methanol solution of sodium methoxide to obtain l-borneol 2-O-β-D-glucopyranoside. The primary hydroxyl group was selectively protected by trityl, followed by acetylation of the secondary hydroxyl groups with acetic anhydride. Next step, detritylation was performed to give l-borneol 2-O-2,3,4-tri-O-acetyl-β-D-glucopyranoside. The optimized reaction conditions of each step were obtained.4. To explore the coupling action of two above intermediates. On the basis of the designed route, the coupling product deprotected acetyl to give final product. NIS/TMSOTf and NIS/AgOTf have been examined, but no expected product was obtained.In conclusion, we have synthesized two key intermediates, p-tolyl 2,3,5-tri-O-acety-1-thioD-apiofuranoside and l-borneol 2-O-2,3,4-tri-O-acetyl-β-D-glucopyranoside. The reaction conditions of each step have been optimized. The following work is to investgate the diferrent catalyst, solvent to obtain l-borneol 2-O-β-D-apiofuranosyl(1â†'6)-β-D- glucopyranoside.