Synthesis Study Of Homoeriodictvol-7-O-β-D-Glycoside And Its Diastereoisomer

As a treasure of the Chinese nation, Chinese medicine has inherited for thousands of years.Finding and exploring new drugs from Chinese medicine has become an important means of drug research and development.Shanghai Institute of Pharmaceutical Industry made a deep research on the treatment for angina caused by coronary heart disease by using mistletoe injection , to develop a new drug and acquire access to the Health Bureau production approval in 1979. But mistletoe injection has not been widely popularized and applied because of some historical reasons.Homoeriodictyol-7-O-β-D-Glycoside is the main component of mistletoe injection, with a wide range of pharmacological activity, but extracting it from mistletoe plants is very difficult because of its low content. In this paper, the first synthesis of Homoeriodictyol-7-O-β-D-Glycoside has been achieved. Our work provided material basis for further pharmaceutical investigation. At the same time, the synthesis of its diastereoisomer has been achieved, to provide a reference for the quality standards study of Homoeriodictyol-7-O-β-D-Glycoside.In this paper, the first synthesis of Homoeriodictyol-7-O-β-D-Glycoside and its diastereoisomer has been achieved, which was carried out by using phloroglucinol and D-glucose as the starting materials through Friedel-Crafts acylation, selective hydroxy protecting, aldol condensation, Michael addition, glycosylation under phase transfer catalytic condition and other reactions. What’s more, we optimized its related reactions and key intermediates.The main contents and achievements of this paper are as follows:(1) The first total synthesis of Homoeriodictyol-7-O-β-D-Glycoside was achieved with a total yield of 5.7% (with phloroglucinol).(2) Optimizing the reaction conditions of the key intermediate 7. Through adjusting the order of the reaction: first Michael addition in the molecule, then removed the MOM protection base from the intermediate 5, with 43% yield in the two steps. The method has not been reported in literature.(3) Exploring the equilibrium conditions of intermediates 5 and 5a. The optimal conditions were as follows: sodium acetate as base, anhydrous ethanol as solvent and reflux for 8 h. Obtaining white powder 5a by column chromatography with 46% yield.At the same time, not fully reacted intermediate 5 can be recycled, the rate of recovery is 40%.(4) The optimal deprotection order of the intermediate 13b was hydrolyzing first to remove the acetyl group to obtain a relatively pure intermediate 14b, then to prepare product lb with higher purity through catalytic hydrogenation.(5) The diastereomer of Homoeriodictyol-7-O-β-D-Glycoside la has no literature reported. In this paper, its first total synthesis was achieved with a total yield of 6.1%through 10 steps reactions (with phloroglucinol).In this paper, the first synthesis of Homoeriodictyol-7-O-β-D-Glycoside and its diastereoisomer has been achieved through the above research and optimization. The raw materials in this synthesis route are inexpensive, the work laid the foundation for large scale preparation of Homoeriodictyol-7-O-β-D-Glycoside to overcome the problem of inefficient extration. It not only provides a large number of samples for its pharmacological research, but also provides reference for other flavonoid glycosides’ synthesis.