- Method for synthesizing glutamic acid-1-methyl ester-5-tert-butyl ester
-
The invention discloses a method for synthesizing glutamic acid-1-methyl ester-5-tert-butyl ester. The method comprises the following steps: generating dimethyl glutamate by using glutamic acid as aninitial raw material in methyl alcohol under the effect of thionyl chloride; reacting the dimethyl glutamate with triphenylchloromethane to generate dimethyl glutamate with triphenylmethyl protected amino; taking off methyl ester on the 5 position of the dimethyl glutamate with triphenylmethyl protected amino under the effect of sodium hydroxide to generate triphenylmethyl-glutamic acid-1-methyl ester; reacting the triphenylmethyl-glutamic acid-1-methyl ester-5-tert-butyl ester with trichloroacetic imine tert-butyl ester to generate triphenylmethyl-glutamic acid-1-methyl ester-5-tert-butyl ester, adding a small amount of triisopropylsilane into the triphenylmethyl-glutamic acid-1-methyl ester-5-tert-butyl ester in a low-concentration dichloromethane trifluoroacetate solution to take off triphenylmethyl to generate the glutamic acid-1-methyl ester-5-tert-butyl ester. The method is simple in operation, has few byproduct which can be extremely easy to treat and high product yield, and cansolve the problem of large operation difficulty in an existing synthesizing method.
- -
-
Paragraph 0027; 0029
(2019/04/13)
-
- Antiviral and tumor cell antiproliferative SAR studies on tetracyclic eudistomins-II
-
In a search for the minimum pharmacophore of the naturally occurring tetracyclic eudistomins, five structural analogues (4-8) were evaluated for their in vitro antiviral and tumor cell antiproliferative activities. For the synthesis of these derivatives both intra- and intermolecular Pictet-Spengler reactions have been used. Opening of the P-carboline annulated 7-membered D-ring in 6 and 7 resulted in a complete loss of activity. On the other hand, replacement of either the oxygen atom or the sulfur atom in the 7-membered ring by a methylene group in 5 and 8, respectively, is allowed. These results combined with previous SAR data underline the crucial importance of the D-ring in eudistomins as a scaffold for the correct positioning of both basic nitrogen atoms. Also bioisosteric replacement of the bicyclic indole system with a dimethoxyphenyl group, to give the isoquinoline skeleton, is allowed. The tricyclic isoquinoline derivative 4 is, so far, the most promising antiviral analogue; it combines a high potency (MIG at 100 ng/ mL (340 nM)) with high MCC/MIC ratios (ranging from 1000 to 5000 against HSV-1, HSV-2, vaccinia virus, and vesicular stomatitis virus).
- Van Maarseveen, Jan H.,Scheeren, Hans W.,De Clercq, Erik,Balzarini, Jan,Kruse, Chris G.
-
p. 955 - 970
(2007/10/03)
-