A kind of preparation method of diacylphosphatidylethanolamine

Abstract

The invention provides a preparation method of diacyl phosphatidyl ethanolamine. The preparation method comprises the following steps: (1) under the action of a solvent and organic alkali / inorganic alkali, carrying out a substitution reaction on a compound as shown in a formula I and a phosphorus reagent to generate an intermediate I as shown in a formula a; (2) in a same reaction system, in the presence of the organic alkali / inorganic alkali of the intermediate 1, carrying out a substitution reaction on the intermediate 1 and 2-(N-fluorene methoxyl carbonyl amino) ethanol or N-Boc protected ethanolamine to generate an intermediate 2 as shown in a formula b; (3) in a same reaction system, carrying out an oxidization reaction on the intermediate 2 under the action of an oxidization reagentto generate a compound as shown in a formula II; and (4) under the action of a solvent and alkali, hydrolyzing a phospholipid head on the compound as shown in the formula II to obtain a compound III.The method has the advantages that a target product can be synthesized with only two steps, and the condition is controllable, the post treatment is simple, side reaction is few, the yield is high, and the demands of industrial production can be met.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a preparation method of diacylphosphatidylethanolamine. Background technique [0002] Phospholipid is a general term for a class of phosphorus-containing lipid compounds. It is the main component of cell membranes and has important physiological functions. Studies in molecular biology and pharmacology have found that phospholipids are involved in many important life activities in organisms, such as cell signal transduction, nerve cell information transmission, lipoprotein metabolism, etc. After years of development, phospholipids have been widely used in the fields of food, cosmetics, health products and pharmaceutical preparations, especially liposome technology. [0003] Among the phospholipids, phosphatidylcholine (also known as cephalin) has the most content, followed by phosphatidylethanolamine (also known as cephalin). Cephalin has a good reducing property, so it is a k...

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Problems solved by technology

[0004] About phosphatidylethanolamine (also known as cephalin), existing similar literature has reported its preparation method at present, as: Marie-Lyne Alcaraz, Ling Peng, Philippe Klotz, Maurice Goeldner et al. Photoactivatable Phospholipid DerivativesDesigned To Probe the Membrane-Associate Domains of Proteins" (J.Org.Chem.1996,61,192-201) proposes a method for preparing octadecyl-distearyl phosphatidylethanolamine: with octadecyl Glyceryl distearate is starting raw material, obtains target product octadecyl carbon distearoyl phosphatidylethanolamine through two-step reaction; The total yield of this synthetic route is 46.5%, is unfavorable for industrialized production, and reaction process is as follows figure 1 shown

But this reaction has the following disadvantages: (1) the first step of this reaction selects POCl 3 to introduce the phospholipid headgroup, POCl 3 Compared with phosphorus reagents, it is more dangerous, has a strong pungent smell, and smokes strongly in the air, while phosphorus reagents are milder; (2) The first step of the reaction is slow and takes a long time, requiring more than 20 hours, the production time is increased, uneconomical; (3) the first step reaction yield of this reaction is low, only 50%, although the productive rate of the second step hydrolysis is higher, there are 93%, but on the whole, the method Difficult to achieve industrial production

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