Mixed condensation method

Acylation of the amine with the methoxime from aminothiazole-glyoxylate has a similar effect on broadening the antibacterial spectmm in the 3-methyl series. In this case, the amine group on the starting thiazole (21-3) is first protected by conversion to (28-2) by alkylation with thriphenylmethyl chloride. Condensation of the acid by the mixed anhydride method with 7-ADC A (26-6) leads to the corresponding amide. The trityl group is then removed to afford the antibiotic cefetamet (28-3) [34]. 

Figure 3.9 Co-condensation method (direct synthesis) employing TEOS and a terminal organotrialk-oxysilane (top) or TEOS and an organo-bridged silsesquioxane (bottom) as mixed precursors for the organic modification of mesoporous pure silica phases. R = organic functional group.

The condensation method makes it possible to obtain more highly dispersed systems than the dispersion method, and true lyophobic sols are always prepared by this method. Colloidal solutions are obtained by the condensation method as a result of chemical reactions of nearly all known types. But it should be noted that sols are by no means always formed, but only in the case of certain concentrations of the original substances, order of their mixing, temperatures of interaction, and a combination of several other conditions. The main method of preparing sols of heavy hydroxides is hydrolysis of solutions of salts, which takes place more completely and more rapidly at high temperatures and in dilute solutions. 

However, the method is not substantially better than the mixed anhydride method, the standard DCC method, the active ester method, or the newer procedures (HBTU, BOP, PyBroP, etc.), and it uses double the amount of N-protected annino acid to accomplish the condensation reaction. Although many synometrical anhydrides are isolable and stable,t l they are not commercially available. On the other hand, the use of preformed symmetrical anhydrides is very convenient. One needs only to add an annino acid ester to the protected amino acid anhydride in a nonreactive solvent and, upon completion of the condensation, destroy the excess anhydride and remove the acid components by extraction. 

In the case of the stepwise synthesis of peptide fragments starting from an amino acid without C-terminal protection, peptide bond forming methods are limited to the mixed anhydride method,the active ester method, and the azide methodJ l Although such peptide fragments can be directly used for the segment condensation reaction, the purification of the products after each coupling reaction is not so easy. 

A useful modification of the Knorr pyrrole synthesis was developed in the laboratory of J.M. Hamby for the construction of tetrasubstituted pyrroles. The necessary a-amino ketones were prepared from A/-methoxy-A/-methylamides of amino acids (Weinreb amides). These Weinreb amides were prepared by the mixed anhydride method and treated with excess methylmagnesium bromide in ether to afford the corresponding Cbz-protected a-amino ketones in excellent yield. The Cbz group is removed by catalytic hydrogenation in the presence of the active methylene compound (e.g., acetoacetic ester), the catalyst is then filtered and the resulting solution is heated to reflux to bring about the condensation. 

In order to determine whether a bridge containing at least two atoms is necessary for antifolate activity, Nair et al. [139] prepared V-[4-(2,4-diamino-6-pteridinyl)methyl]benzoyl-L-glutamate ( 9-nor-lO-deaza-AMT (IV. 160)). 1-Bromo-3-(4-methoxycarbonylphenyl)-2-propanone was converted by a series of standard reactions to the azido ketal acid (IV. 161), which was condensed with diethyl L-glutamate by the mixed anhydride method to form the diester (IV. 162). Reduction of the azido group followed by reaction with 2,4-diamino-... 

With keto-ester condensations the procedure of first converting the ketone to be acylated to its sodio derivative and then adding the acylating ester, employed previously with sodium amide (1) has generally not been satisfactory with sodium hydride, as considerable self-condensation occurs. The general method adopted for mixed condensations by sodium hydride consists in slowly adding the com-... 

Thus, increase of intensity of turbulent mixing allows production of fine systems "solid-liquid". Furthermore, reactions underlying the condensate method of their reception proceed fast. This determines expediency of studying of tubular turbulent apparatus application possibility in particular divergent-convergent design for preparation of homogeneous fine suspensions by condensate method under fast chemical reaction. 

Yet another area where liposomes are of interest is gene therapy (48, 92-97). Thus, on mixing lipids with DNA, compact complexes may be obtained, particularly for cationic lipids. More specifically, most DNA condensation methods yield similar particles, i.e. torus-shaped with a 40-60 nm outer and 15-25 nm inner diameter, or rods of about 30 nm in diameter and a length of 200-300 nm, although this naturally depends on a number of parameters, such as the lipid/DNA ratio (48). By... 

Incorporation of the Cu(II) complex to the mesopore surface was accomplished by the aforementioned co-condensation method using a methanolic solution of Cu(II) complex as a precursor. The solution was prepared by mixing copper(II) bromide and N-(2-aminoethyl)-aminopropyltrimethoxysilane (AAP-TMS). The measurements of... 

The introduction of azobenzene units in the side chains of poly(L-lysine) been achieved by means of various procedures and different azo-reagents. In some experiments, samples of poly(Lysine HCl) or poly(Lysine acetate) were reacted with p-phenyl azobenzoic acid in the presence of pivaloyl (trimethylacetyl) chloride (mixed anhydrides method). Although anhydrous conditions must be maintained during the preparation of the anhydride itself, the condensation reaction with the amino compound can be performed in aqueous medium. This is necessary in this case, as poly(Lysine) is insoluble in pure DMF and other organic solvents commonly used in peptide synthesis. 

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