A novel and practical synthesis of iclaprim

A novel and facile synthesis of iclaprim was reported. Started from Trimethoprim (TMP), the amino-protection and Friedel-Crafts acetylation with acetic anhydride were simultaneously completed in CH2Cl2 with SnCl4 as catalyst. The Knoevenagel condensation of 2,4-diamino-5-(2-acetyl-3-hydroxy-4,5-dimethoxybenzyl)pyrimidine with cyclopropyl carboxaldehyde followed by the intramolecular Michael addition in the buffer system (pyrrolidine and acetic acid) installed the key framework (chromanone 13). The dehydration was catalyzed by H2SO4 so that the formation of 5-cyclopropyl-2,3-dimethoxy-4,5,6,6a,7,12-hexahydronaphtho[1,8-bc]pyrimido[5,4-f]azepin-9-amine, an impurity of iclaprim reported at the first time, could be minimized. In the end, iclaprim was obtained in a total yield of 21%.

Simple, Efficient, and Selective Synthesis of Phthaloylserine and Phthaloylthreonine

An amino protection method was developed in which phthalic anhydride was used as the amino protection group, N,N-dimethylformamide (DMF) as solvent, L-threonine and L-serine with hydroxyl groups in side chain as the protected amino acids.The structures of products were confirmed by IR、1H NMR and 13C NMR. It is an efficient and simple protection method of amino acids with a hydroxyl group in the side chain.In addition, the synthetic method avoids the side reaction and significantly improves reaction yields(over 90%).

Approaches to α-amino acids via rearrangement to electron-deficient nitrogen: Beckmann and Hofmann rearrangements of appropriate carboxyl-protected substrates

The titled approaches were effected with various 2-substituted benzoylacetic acid oximes 3 (Beckmann) and 2-substituted malonamic acids 9 (Hofmann), their carboxyl groups being masked as a 2,4,10-trioxaadamantane unit (an orthoacetate). The oxime mesylates have been rearranged with basic Al2O3 in refluxing CHCl3, and the malonamic acids with phenyliodoso acetate and KOH/MeOH. Both routes are characterized by excellent overall yields. Structure confirmation of final products was conducted with X-ray diffraction in selected cases. The final N-benzoyl and N-(methoxycarbonyl) products are α-amino acids with both carboxyl and amino protection; hence, they are of great interest in peptide synthesis.

The Preparation of O-Carboxymethyl-Chitosan and its Particles

The active site of chitosan is protected basing on amino reaction method of reaction between benzaldehyde and chitosan to form Schiff. The O-carboxymethyl chitosan is obtained by the method that taking chloroactic acid to hydroxyl of chitosan as modifier in alkaline conditions to form amino protection and then remove the protection in acid conditions. The O-carboxymethyl chitosan particles with particle size distribution of 15-50μm is prepared by emulsification cross- linking method.