Transamidation reactions

The transamidation reaction can be performed with a large variety of bases, but no systematic investigation has been undertaken. Examples of bases are potassium 3-aminopropylamide in 1,3-diaminopropane (=KAPA) [3] [4], quinoline [5], NH3 in a sealed tube [6], KOtBu in different solvents [7], NaOC2H5 in toluene [7], K0H/CH30H/H20 [7] [8], and KF in dimethylformamide/[18]-crown-6 [9]. Under acidic conditions, p-toluolsulfonic acid is a proper catalyst [10]. 

The smallest ring which has been enlarged by this method was the four-mem-bered one. Thus, the N-(haloalkyl)-derivatives VI/11 were prepared from 4- 

1) Even without any additional reagents VI/4 converts to its isomer, VI/9, after one year in a sealed tube. 

This proved that the seven-membered compound, VI/16, with a tertiary lactam nitrogen atom is more stable than the eleven-membered azalactam, VI/17 with a secondary lactam nitrogen atom. This result seems to be contradictory to the 

2) Depending on their structural details, bicyclic amidines and amidinium salts hydrolyzed by K0H/H20 give ring-enlarged or ring-contracted lactams when hydrolyzed by K0H/H20 [8]. 

Since the initial work in 1996 from Venton and coworkers on the dynamic screening (under conditions in which both hydrolysis and synthesis occurred in the presence of proteases) of a peptide library for the discovery of novel peptides that bind to fibrinogen [3], many efforts have been made to perform amide exchange in 

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Recently, such a procedure has been used by Wu and Shanks [22] upon a preparation of partially hydrophobized polyacrylamide (PAAm). In this work, the transamidation reaction has been employed to convert amide groups of the parent polymer to the alkylamide groups of the modified PAAm. Scheme 2 shows the reaction chart for the case of the N-isopropylamide derivative. 

Another degradation reaction observed in suspension was the formation of covalent insulin dimers [134][136], These involve isopeptide links between two insulin molecules, that result from a transamidation reaction mainly between the B-chain N-terminus of one insulin molecule, and one of the four amide side chains in the A-chain (principally AsnA21) of the second insulin molecule. 

Table 2 contains the characteristics of the amic ester-aryl ether copolymers including coblock type, composition, and intrinsic viscosity. Three series of copolymers were prepared in which the aryl ether phenylquinoxaline [44], aryl ether benzoxazole [47], or aryl ether ether ketone oligomers [57-59] were co-re-acted with various compositions of ODA and PMDA diethyl ester diacyl chloride samples (2a-k). The aryl ether compositions varied from approximately 20 to 50 wt% (denoted 2a-d) so as to vary the structure of the microphase-separated morphology of the copolymer. The composition of aryl ether coblock in the copolymers, as determined by NMR, was similar to that calculated from the charge of the aryl ether coblock (Table 2). The viscosity measurements, also shown in Table 2, were high and comparable to that of a high molecular weight poly(amic ethyl ester) homopolymer. In some cases, a chloroform solvent rinse was required to remove aryl ether homopolymer contamination. It should also be pointed out that both the powder and solution forms of the poly(amic ethyl ester) copolymers are stable and do not undergo transamidization reactions or viscosity loss with time, unlike their poly(amic acid) analogs.

Cefoxitin Cefoxitin, 3-(hydroxymethyl)-8-oxo-7-methoxy-7-[(2-thienylacetyl)amino]-5-thia-l-azabicyclo[4.2.0]oct-2-en-2-carboxylic acid carbamate (32.1.2.30), is synthesized in various ways starting from cefamicin C-7)3-(D-5-amino-5-carboxyvaleramido)-3-aminocarbonylhydroxymethyl-7-methoxy-3-cefem-4-carboxylic acid, in which a methoxy group is initially present at C, and the task of making the desired drug essentially consists of a transamidation reaction. 

The molecular weight increases with increasing conversion. Regulation of the molecular weight can be achieved by adding small amounts of substances (e.g., benzoic acid) that can react with the polyamide chains by transamidation. Because of the transamidation reaction and hydrolysis of amide bonds, an equilibrium molecular-weight distribution is finally attained (see Sect. 4.1). 

The action of bases on caprolactam or amide groups of the polymer molecule is not limited to the disproportionation and transamidation reactions which are directly involved in the polymerization mechanism. A more detailed study of the polymerization kinetics has shown that the... 

Although transesterification and transamidation reactions of simple carbonyl ligands are usually associated with the involvement of a co-ordinated nucleophile, there are some well-documented processes which unambiguously involve attack by an external nucleophile upon a co-ordinated electrophile. Dithiocarbamate complexes contain a chelated. S, 5"-bonded dithioamide ligand and undergo facile transamination reactions upon treatment of the copper complexes with amines (Fig. 3-22). 

The degradation products of interlayers can be adjusted to the purposes of FR by including FR-active elements such as phosphorus (P) into the surface modifier molecule [26], The reactive formation of such interlayer around CNT has been performed by a transamidation reaction, shown in Scheme 13.3. 

Although a structure was published for VI/1, it was not crystallized, despite many attempts at purification. By TLC, samples of oncinotine always seemed to contain some iso-oncinotine (VI/3). Subsequently, it was learned that the crude oncinotine contained another isomer, VI/2, neo-oncinotine, but no iso-oncinotine. During the purification attempts, it appeared that VI/2 was converted to VI/3 (Scheme VI/1) [2]. This reaction has been the starting point of a series of investigations in the field of transamidation reactions. 

Aminoamides such as VI/4 are instable they rearrange under acid or base (shown) catalysis to VI/91. The mechanism of this reaction is shown in Scheme VI/2 [3]. The driving force of this transamidation reaction seems to be the formation of the anion VI/8, which is resonance stabilized and so more attractive than the alternative anion VI/5. 

Using this transamidation reaction, it is possible to introduce three to six ring members in one step, which means that the intermediate ring (see Scheme VI/2) can be five- to eight-membered [6] [7] [11]. The preferred ring size is five to seven eight-membered intermediates seem to occur only if a /1-lactam is used as starting material [6]. 

Scheme VI/2. Mechanism of the base catalyzed transamidation reaction [3].

Scheme VI/4. Ring contraction by transamidation reaction [7]. a) KAPA.

Further transamidation reactions are depicted in Scheme VI/6. In some respects, even the Gabriel synthesis, [15] [16] [17]3), a method for preparation of primary amines from N-substituted phthalimides by treatment with hydrazine,... 

Transamidation reactions of open chained systems have been known for many years. Treatment of acetamide with aniline leads to acetanilide and ammonia [18]. Similar reactions with hydrazine [19] [20], and with other amines [21] [22] have been described. 

One of the great advantages of the transamidation reaction is that it can be repeated. If the 13-membered lactam, VI/35, (R=H) with a 7-amino-4-azahep-tyl substituent located at the lactam nitrogen atom is treated with the KAPA reagent, the intermediate VI/36 should be formed first, see Scheme VI/7. 

Scheme VI/7. The transamidation reaction as a repeatable ring expansion process [30].

The coumarin derivative, VI/41, can be similarly converted into the 14-mem-bered lactam VI/43 [35]. The first step in this transformation is probably the conjugate addition of a primary amino group of l,9-diamino-3,7-diazanonane (VI/42) to the a,/ -unsaturated lactone, VI/41, followed by lactone aminolysis and two transamidation reactions (Scheme VI/9). For additional results see ref. [36]. 

The transamidation reaction has been successfully applied to the syntheses of a number of natural polyamino alkaloids. These alkaloids contain principally spermidine or spermine as the basic skeleton [37],... 

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