P-Amination

Schiller, P., Amin, J., Ananthan, J., Brown, M.E., Scott, W.A., Voellmy, R. (1988). Cis acting elements involved in the regulated expression of human hsp70 gene. J. Mol. Biol. 203, 97-105. 

Collignon, N., Fabre, G., Varlet, J.-M., and Savignac, P., Amination reductrice d aldehydes phosphoniques, un reexamen, Phosph. Sulf, 10, 81, 1981. 

This mechanism is of importance in radical induced amino acid damage catalyzed by copper ions. The study of the decomposition of transients with a metal-carbon -bond containing two potential leaving groups (both an amine and a carboxylate group) at the p position of the carbon centered radical is of special interest. It was reported that the intermediate formed with the amino acid 2-methylalanine with cupric ions decomposes via p-carboxyl elimination whereas the intermediate formed with cuprous ions decomposes via p-amine elimination (102). 

P,y-Diamino analogues 49 of statine are prepared stereoselectively starting from the O-methyl hydroxamate derivative of N-protected statine. The reaction sequence involves the formation of a p-lactam intermediate obtained by internal cyclization under Mitsunobu conditions.184 Alternatively, direct amination of either a p-oxo ester 31 followed by reduction of the resulting enamine 50, 85 or by reduction of the corresponding ,p-unsaturated ester, 88 gives an enantiomeric mixture of the corresponding unprotected p-amine, which is protected by a carbamate prior to chromatographic separation (Scheme 20). 

Carboxy terminal amino acid or peptide thiols are prepared from various p-amino alcohols by conversion into a thioacetate (R2NHCHR1CH2SAc) via a tosylate followed by saponification.Several methods have been used to prepare N-terminal peptide thiols, the most common procedure is the coupling of (acetylsulfanyl)- or (benzoylsulfanyl)alkanoic acids or add chlorides with a-amino esters or peptide esters, followed by deprotection of the sulfanyl and carboxy groups. 8 16 Other synthetic methods include deprotection of (trit-ylsulfanyl)alkanoyl peptides, 1718 alkaline treatment of the thiolactones from protected a-sulfanyl acids, 19 and preparation of P-sulfanylamides (HSCH2CHR1NHCOR2, retro-thior-phan derivatives) from N-protected amino acids by reaction of P-amine disulfides with carboxylic acid derivatives, followed by reduction. 20,21 In many cases, the amino acid or peptide thiols are synthesized as the disulfides and reduced to the corresponding thiols by the addition of dithiothreitol prior to use. 

A more detailed study [6] showed the P-amination of an unsaturated ketone and the formation of adduct 2 (Scheme 4.1) to be the first stage of this reaction. Later the general character of the interaction between 0-PDA and substituted ketones or their vinylogs was established [7, 8]. Unsuccessful attempts [7] to synthesize aromatic dihydrobenzodiazepine derivatives from 1,2-diaminoan-thraquinone, 4-nitro-, 4-nitrile-4,6-dichlor- and TV-phenyl-substituted 0-PDAs were also reported. Condensation of 0-PDA with 0r /z0-hydroxychalcone 5... 

Further search for inverse substrates other than /7-amidinophenyl esters has been carried out and it has been found that esters derived from p-amin omcthylphcnol and /7-guanidinophenol were also eligible as a substrate of trypsin and trypsin-like enzymes 75 86). We have also found that trimethylaminobutanoic acid p-nitrophenyl ester is an inverse substrate for butyrylcholinesterase 87-88(. Application of the inverse concept to thiol enzymes was also successful p-amidinophenyl esters were found to be substrates for clostripain 74), a thiol enzyme with trypsin-like specificity. Although the design of inverse-type substrates seems not always possible for a variety of hydrolytic enzymes, this new concept could provide potential means for certain enzymes to both fundamental study and application. 

Sayari et al. [209-212] followed another path to the synthesis of mesolamellar aluminophosphates. They used AI2O3, H3PO4 and primary or tertiary amines as surfactants in aqueous media. The surfactant was found to be protonated while acting as template. Effects of synthesis parameters such as Al/P, P/amine, P/H2O ratios were studied systemically by XRD and Al and P NMR. The connectivity between Al and P was found to be dependent on the synthesis parameters. 

The equivalent 14-aminodihydrocodeinone (20a) can be reached by direct hydrogenation of (13) (Scheme 4) [11, 14], giving an overall yield for the thebaine to 14 p - amin odihydrocodeinone conversion in the range 50-60%. A more direct... 

The transformation of the PPB group to a more readily cleaved benzyl group has been exploited in carbohydrate synthesis. This transformation is accomplished with 4,4 -di-f-butylbiphenylide (LDBB). Since the 4-ClBn group (PCB) is less reactive to Pd-catalyzed substitution with an amine, the PPB group can be selectively converted to a p-amine derivative which may then be cleaved with SnCLi, dichloroacetic acid, TFA, ZnCl2, TiCLt or CAN. After derivatization of the alcohol as a propyl ether, the PCB group was removed similarly. 

More modem, much faster responding liquid crystalline displays use ferroelectric liquid crystals such as p-decyloxybenzylidine-p -amine-2-methylbutylcinnamate, which can be switched between two stable states by application of an external field. Such properties may also be useful in optical data storage. 

Phenol or phenol ethers with other functional groups are listed in Sections 5.P (amines) and 5.Q (sulfur compounds). 

Specific decarboxylases are known for a majority of the amino acids, and several are prime targets for inactivation by virtue of their substantial medicinal importance. These include aromatic-amino-acid decarboxylase, which is responsible for the production of dopamine (DOPA) orithine decarboxylase, which supplies the p amine putrescine and glutamate decarboxylase, which converts glutamate to the inhibitory neurotransmitter y-aminobutyric acid (GABA). The accepted mechanism of these enzymes involves decarboxylation of the amino acid to yield a resonance-stabilized carbanion at the a-carbon of the substrate. The intermediate is then protonated with retention of configuration to yield product (Walsh, 1979, p. 800). 

Halcrow, M. Phillips, S. Knowles, P. Amine oxidases and galactose oxidase. In Subcellular Biochemistry, Vol. 35 Enzyme-Catalyzed Electron and Radical Transfer Holzenburg, A. Scrutton, N. S., Eds., Plenum New York, 2000 pp 183-231. 

A later-developed method to obtain amines from azides consists in their reduction with propane-1,3-dithiol,employing ethyldiisopropylamine as a base. The transformations reported proceeded rapidly and resulted in, 2-trans selectivity. Unverzagt described the reduction of the azido heptasaccharide 221 by this dithiol method, to give exclusively the p amine 222. In contrast, reduction of 221 by Raney nickel resulted in both anomers 222 and 223, with p a = 7 3. A corresponding reduction of the azido octasaccharide gave a 52% yield however, a low yield of 35% was observed in the reduction of the thio sugar azide 68 with propane-1,3-dithiol... 

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