N-methylamides

R. J. Loncharich, B. R. Brooks, and R. W. Pastor. Langevin dynamics of peptides The frictional dependence of isomerization rates of N-acetylalanyl-N -methylamide. Biopolymers, 32 523-535, 1992. 

The importance of ring size holds also for tautomerism of -pyrrol-5-ones and. d -dihydro-6-pyridones. While the former compounds behave as cyclic 1-methyl-2-alkyl-2-hydroxy-5-pyrrolidones 179) (76) [or, on distillation, as the dehydrated l-methyl-2-alkyl-J -pyrrolones (77)], the latter compounds exist as acyclic N-methylamides of 8-oxo-acids (78) [as shown by infrared spectroscopy (/80)j. The dehydration of 78 during distillation to form l-methyl-2-alkyl-. -dihydro-6-pyridones (79) is achieved only with difficulty. 

The same nonpolar conformation can be achieved by conversion to bicyclic structures. 1,4-Cyclo-addition of ethylene to anthracene-9-carboxylic acid gives acid 68. Successive conversion to the N-methylamide, via the acid chloride, followed by reduction with lithium aluminum hydride produced... 

B. Theoretical Studies of Aqueous iV-Acetyl-L-alanine N-Methylamide. 172... 

Diketopiperazine formation is a reaction that occurs specifically at the N-terminus of peptides and leads to cleavage of the first two residues. Glycylgly-cine N-methylamide (6.56) has proven to be particularly useful as a model compound in investigations of the mechanism and kinetics of the reaction as compared to the reactivity of analogues 6.40, 6.43, and 6.45 discussed in Sect. 

The energetics of Phe provide an excellent example of this phenomenon. In our molecular dynamics simulation of vasopressin, we found that Phe underwent conformational transitions between three regions of conformational space the 7 (, = -80, -1-80), a, (, i/i = -E80, -80) conformations(64). These conformations in the isolated residue, taken as the N-acetyl, N -methylamide blocked phenylalanine, are well separated energetically as can be seen in Table I. The C7 is 3.1 Kcal more stable than the 7 , and 4.7 Kcal more stable than the a,. In order to compare the relative stabilities of these phenylalanine conformations in the... 

N-Acetylalanyl N -methylamide, 2ll3f Aclacinomycin A, 8i1,87f Acridine orange intercalator, 125f Adrenocorticotropic hormone (ACTH) D-amino acids and activity, 155-58 biological and physicochemical properties, 158-62 chain length and... 

Walpole, C., Ko, S. Y., Brown, M., Beattie, D., Campbell, E., Dickenson, F., Ewan, S., Hughes, G. A., Lemaire, M., Lerpiniere, J., Patel, S., Urban, L. 2-Nitrophenylcarbamoyl-(S)-prolyl-(S)-3-(2-naphthyl)alanyl-N-benzyl-N-methylamide (SDZ NKT 343), a potent human NK1 tachykinin receptor antagonist with good oral analgesic activity in chronic pain models, J. Med. Chem. 1998b, 41, 3159-3173. 

The rates of hydrolysis and carbonyl-oxygen exchange of 0-labeled N-benzyl-N-methylamides 34 (R=H, CD3 and CD2CH3) were carefully measured at several temperatures in 83 0 (18). The activation parameters, found by plotting... 

Ammonium formate Phenylalanine-N-methylamide Formaldehyde Dicyclohexylcarbodiimide... 

The [4-hydroxy-2R-isobutyl-3-ethenylsuccinyl]-L-phenylalanine-N-methylamide (400.0 mg, 1.16 mmol) was dissolved in thiophenethyol and the mixture stirred in the dark under nitrogen at 60°C for 2 days. Ether was added to the cooled reaction mixture and the precipitated product collected by filtration. 

The solid was washed with large volumes of ether and dried under vacuum to give the [4-N-hydroxy-2R-isobutyl-3S-(thienylthiomethyl)succinyl]-L-phenylalanine-N-methylamide (320.0 mg, 0.73 mmol, 63%), melting point 184°-186°C. 

The [4-N-hydroxy-2R-isobutyl-3S-(thienylthiomethyl)succinyl]-L-phenylalanine-N-methylamide and hydroxy benztriazole were dissolved in DCM/DMF (4 1) and the mixture cooled to 0°C before adding N-(dimethylaminoethyl)-N -ethylcarbodiimide and N-methylmorpholine. The mixture was stirred at 0°C or 1 h to ensure complete formation of the activated ester. Hydroxylamine hydrochloride and NMM were dissolved in DMF then this mixture added dropwise to the cooled solution of the activated ester. After 1 h the reaction was poured into ether/water (1 1) whereupon the desired product precipitated as white crystals. These were collected by filtration, further washed with ether and water then dried under vacuum at... 

C. So the [4-(N-hydroxyamino)-2R-isobutyl-3S-(thienylthiomethyl) succinyl]-L-phenylalanine-N-methylamide was obtained, melting point 236°-238°C (recrystallised from methanol/ water 1 1). 

Figure 3.1 Dihedral angles and i/r for tyrosyl dipeptide analogue (a-acetylamino-tyrosyl-N-methylamide, TDA).

Tetra-p-methoxyphenylporphyrin Tetra-p-sulfophenylporphyrin Glycylglycyl-l-histidine-N-methylamide jV,A"-Ethylenebis(2-hydroxypropiophenoneimine) Hexafluoroacetylacetone The tripeptide of a-aminoisobutyric acid cis-1,2-Dicy anoethylene-1,2-dithiolato Al-(4-Imidazolylmethylidyneimine)-N -(2-hydroxy-5-chlorobenzyliphenoneiminelphenylene Tetra-n-butylammonium 5,10,15,20-Tetra-p-chlorophenylporphyrin 1,4-Bis( 1 -oxa-4,10-dithia-7-azacyclododecan-7 -y lmethyl Ibenzene Bis[AlA/ -bis(2-... 

The identification of the A-methylamine (XXVII) and the N-methylamide (XXVIII) during the reductive hydrolysis of AIC raised the prospect that these byproducts might be avoided if the reduction step was separated from the hydrolysis step. 

M. P. Sibi, Chemistry of N-Methoxy-N-Methylamides. Applications in Synthesis, Org. Prep. Proced. Int. 1993, 25, 15 10. 

Table VII (polyester-polyamide) shows that in our series the polyamides have glass temperatures which are 100 °C. or higher than those of polyester. Probably the differences of glass temperatures of 100 °C. between polyamides and analogous polyesters are caused not only by the hydrogen bridges but also by polarity. It can be assumed that the polyamide with the N-methylamide structure (no H bridges) has a higher glass temperature than the analogous polyester.

Leiserowitz, L. and Tuval, M. (1978). Molecular packing modes N-methylamides. Acta Crystallogr. B34, 1230. 

Jalkanen K, Suhai S (1996) N-Acetyl-L-alanine N -methylamide a density functional analysis of the vibrational absorption and vibrational circular dichroism spectra Chem Phys 208 81-116... 

In Table I we report the thermodynamics describing the equilibrium between a series of conformations of N -acetyl-(alanyl)3-N methylamide. The potential energy of this molecule, as given by equation (2), was minimized with respect to the cartesian coordinates of all atoms in the molecule. Four initial "helical" conformations were minimized, C7ea, C7ax, < r and cu. (These conformations are shown in Figure 4 for the nonapeptiae). 

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