Synthesis of Sialidase Detection Agent(X-Neu5Ac)†

doi:10.7503/cjcu20160811

Abstract

Abstract:

The sialic acid methyl ester was synthesized via the methanol esterification of sialic acid under the catalysis of concentrated sulfuric acid, and yield increased by 20% compared with all previously reported literatures. In the following acid chloride reaction, the yield of compound 4 increased from 86.4% to 98.9%. Compound 4 was condensed with compound 6 in the presence of sodium hydride in tetrahydrofuran(THF) and then was hydrolyzed by MeONa to obtain the target product(X-Neu5Ac). The process adopted the catalytic method of concentrated sulfuric acid to get compound 2. The results indicate that the accessible raw material and safe operation avoided the use of expensive resin and the exist of dangerous diazomethane. Meanwhile, the one-pot method in acid chloride reaction benefited the reaction of acetyl protection and chlorination. As the key intermediate, the synthesis condition of compound 7 was optimized by single factor experiment to obtain the optimal reaction condition: the reaction temperature of 25 ℃, reaction concentration of 200 mL solvent per 10 g substrate, the reaction time of 10 h. By detecting the active ingredient in X-Neu5Ac, the stability and color sensitivity of products met relevant requirement and its structural properties were characterized by means of ¹H NMR, ESI-MS and HPLC-MS.

Key words: Sialic acid, X-Neu5Ac, Key intermediate, Chromogenic reaction

CLC Number:

O621.25

TrendMD:

LEI Xiong, ZHU Chenhui, GUO Hongyao, WANG Xiaojing, HU Weiyue, WANG Feng, LI Wenhong. Synthesis of Sialidase Detection Agent(X-Neu5Ac)^†[J]. Chem. J. Chinese Universities, 2017, 38(3): 398.

Figures/Tables 7

Scheme 1 Synthetic route of target compound X-Neu5Ac

Scheme 2 Synthesis route of compound 7

Scheme 3 Chromogenic reaction of compound X-Neu5Ac

Table 1 Effect of temperature on the reaction yield

T/℃	0	10	25	40	50	60
Yield(%)	21	51	61	60	59	45

Table 2 Effect of the volume of solvent on the reaction yield

V/mL	10	20	50	100	200	300
Yield(%)			27	65	80	80

Table 3 Effect of reaction time on the reaction yield

t/h	0.5	1	2	4	8	10	12
Yield(%)	15	25	31	54	78	80	80

Fig.1 Activity of positive(A)—(E) and negative(F) of X-Neu5Ac experiment chromogenic reaction results

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