Mitsunobu Reaction
Synthesis of Selective β-lactam Derivatives
Thu, 2013-02-14 23:00 — Iyad AliIn this work, the mild conditions of Mitsunobu reaction were used to convert the hydroxyl group of 6-triphenylmethylaminopenicillanyl alcohol to amines by using different nuleophiles such as phthalimide, di-tert-butyliminodicarboxylate and potassium cyanate. The existence of the β-lactam carbonyl group increased the instability towards nucleophilic attack of refluxing methanol and the four-membered ring was opened. Treating 3-Di-tert-Butoxycarbonylaminomethyl-6-triphenylmethylamino - penicillanate with 50% trifluoroacetic acid in dichloromethane, resulted in the cleavage of triphenylmethyl group and one tert-butyl group. While the removal of both triphenylmethyl groups as well as di-tert-butylamino carbonyl group occurred when 75% trifluoroacetic acid was used. The significance of this study is to synthesize β-lactam derivatives that might to be more resistant to degradation by β-lactamase and hence, therapeutically more effective.
Facebook
Google
LinkedIn
TwitterSynthesis of a Novel β-lactamase Hydrolysis Resistant Penicillin Analog
Sun, 2011-02-27 11:35 — Iyad AliIt has been suggested that Lys234 residue participates in -lactamase catalysis by acting as an electrostatic anchor for the C-3 carboxylate of penicillin. The aim of the present work is to test the role of the carboxylate group at C-3 in binding with the enzyme. A novel penicillin derivative, 3-aminomethyl-6-phenylacetamidopenicillanate, was prepared in which the carboxylic acid group at C-3 was replaced by an amino group. This was achieved by the reduction of a mixed anhydride of penicillin G to obtain 6-phenylacetamidopenicillanyl alcohol. The behavior of the alcoholic function in reacting with acidic components, following Mitsunobu reaction, was investigated, and 3-di-tert-butoxycarbonylaminomethyl-6-phenylacetamidopenicillanate was prepared as a crude product. After purification using column chromatography, the crude product undergoes deprotection of the amino group to produce the desired compound 3-aminomethyl-6-phenylacetamidopenicillanate. The hydrolysis of this compound by β-lactamase and the altered β-lactamase was determined and studied. The alteration in -lactamase was done by changing the lys234 residue to glutamic acid residue using site specific mutagenesis.
