High-efficiency preparation method of D-dencichine

Abstract

The invention relates to a high-efficiency synthesis method of a hemostasis compound D-dencichine, comprising the following steps: firstly enabling D-serine to react with di-tert-butyl dicarbonate ester to generate Boc-D-serine, then generating Gabriel reaction with hydroxy of methylsulfonyl chloride activated Boc-D--serine to obtain N-alpha-Boc-D-alpha, beta-diaminopro, finally condensing with oxalate mono-methyl ester sylvite then performing hydrolytic acidification to obtain a dencichine crude product, and purifying to obtain a dencichine competitive product, with the product content reaching more than 99.8%. Compared with existing D-dencichine synthesis methods, the reaction condition is more mild, the operation is simple and convenient, the material cost is relatively low, and the hemostasis compound D-dencichine is environment-friendly, is suitable for industrial production, and solves the problem of resource for later development of clinical trial of D-dencichine.

Description

technical field [0001] The invention is a high-efficiency preparation method of the hemostatic compound D-notoginsin (ie β-N-diacetyl-D-α, β-diaminopropionic acid). Background technique [0002] Panax notoginseng, also known as Tianqi, belongs to the dry root of Panax notoginseng belonging to the genus Panax notoginseng of Araliaceae. It is used for hemoptysis, hematemesis, epistaxis, blood in the stool, metrorrhagia, traumatic bleeding, tingling pain in the chest and abdomen, and swelling and pain from tumbling. "Compendium of Materia Medica" records: Hemostasis, dispersing blood and relieving pain, for golden blade arrow wounds, falling stick sores, and bleeding, chew and apply it, or mix it at the end, the blood will stop immediately, mainly vomiting blood, epistaxis, and bleeding Bloody dysentery, metrorrhagia, persistent menstrual flow, postpartum hemorrhage, pain in blood circulation, red eyes and carbuncle, tiger bites and snake bites. "Compendium of Materia Medica S...

AI Technical Summary

Problems solved by technology

Among them, p-toluenesulfonyl chloride is used as a raw material for amino protection, which has a strong taste, bromine and hydrogen bromide, very polluting, waste water, waste gas, environmental pollution problems are relatively large, and industrial production is more difficult.

CN105439883 reported a synthetic method of D-notoginseng, using D-asparagine as raw material, Fmoc protection, using PIFA for Hoffman degradation, after de-Fmoc protection, condensation with monomethyl oxalate potassium salt to obtain D - Panax notoginsin, among which the Fmoc protective agent and PIFA are relatively expensive, and piperidine is required to deprotect Fmoc, which is toxic and belongs to the precursor raw material, and it is difficult to purchase, thus limiting industrial production

CN105061247 reported a synthesis method of L-notoginsin, using iodobenzenediacetic acid as raw material to perform Hoffmann degradation to obtain N-α-Boc-L-α, β-diaminopropionic acid, which was obtained in 1,4-diaminopropionic acid Oxyhexane is condensed with oxalyl chloride and then quenched to obtain L-notoginseng. Iodobenzenediacetic acid is more expensive and because N-α-Boc-L-α, β-diaminopropionic acid has a higher solubility in organic solvents Poor, there will be incomplete reaction during the reaction, such shortcomings as difficulty in stirring, and the oxalyl chloride has a very pungent odor, is volatile and deteriorates, and has a high reactivity, and is easy to produce by-products. After the reaction, it will release a lot of heat and Hydrogen chloride is released, the pollution is relatively large, and it is not conducive to the scale-up of production

Images