Acylations hydro

Another substitution reaction that is initiated by photochemical hydrogen abstraction is the replacement of the bromine atom in 2-bromo-8-methoxy-l, 4-naphthoquinone by an acyl group757. Irradiation of a solution in benzene of the quinone, butyraldehyde or capraldehyde and pyridine yields mixtures of acylated quinone and acylated hydro-quinone. In the first step, the excited quinone abstracts the aldehyde hydrogen atom and this is followed by bond formation between the acyl radical and C-2 of the quinone. The radical that is formed after departure of a bromine atom may either lose a hydrogen atom and yield acylated quinone or take up a hydrogen atom and become acylated hydro-quinone. 

A direct approach to a-amino phosphonic acids derivatives (594) has been developed by McDonald and Wang. Thus, copper-catalysed electrophilic amination of a-phosphonate zincates (592) with O-acyl hydro-xylamines (593) (Scheme 172) provided the first example of C-N bond formation which directly introduced acyclic and cyclic amines (592) to the a-position of phosphonates (591) in one step. ° ... 

Intramolecular acylation of suitably 1-substituted 1,2,3,4-tetra-hydro-/8-carbolines has been studied. It has been stated that... 

The side chain hydroxy group of 3-(2-hydroxyethyl)-2-methyl-9-methoxy-4//-pyrido[l,2-u]pyrimidin-4-one, and that of its 6,7,8,9-tetrahydro derivative was acylated with MeS02Cl in the presence of NEts in CH2CI2 at room temperature (95MIP4, 96MIP2). The hydroxy group of 2-[4-(4-hydro-xybenzoyl)benzyloxy]-3-methyl-4//-pyrido[l, 2-u]-pyrimidin-4-one, its 6-methyl derivative and 2-[4-(4-hydroxybenzoyl)benzylthio]-3-methyl-4//-pyrido[l, 2-u]pyrimidin-4-one was alkylated with 4-(2-chloroethyl)morpholine hydrochloride and 4-picolyl chloride hydrochloride (96EUP733633). 

Similarly in epimeric transformation of A/ -acyl derivatives of 1,3-diphenyl-3-aminopropanol, the formation was accepted of 5,6-di-hydro-l,3-4H-oxazines with a conformation similar to (61). 

Auch cyclische Acyl-thioharnstoffe vom 4-Oxo-2-thiono-imidazolidin- bzw. -te-tra(hexa)hydro-pyrimidin-Typ lassen sich selektiv an der Carbonyl-Gruppe zu den ent-sprechenden 2-Thiono- (mit Lithiumalanat) bzw. 4-Hydroxy-2-thiono-Verbindun-gen (mit Alkalimetallboranat) reduzieren z. B. ... 

Unlike alkylation, Friedel-Crafts acylation has been generally considered to be irreversible, but a number of instances of electrofugal acyl groups have been reported, especially where there are two ortho substituents, for example the hydro-de-benzoylation of 42. ... 

See Dawson, I.M. Hart, L.S. Littler, J.S. J. Chem. Soc., Perkin Trans. 2, 1985, 1601. This is the name for the para migration. For the ortho migration, the name is l/C-hydro,3/ 0-acyl-interchange. 

Basic Cleavage of P-Keto Esters and p-Diketones Hydro-de-acylation... 

The starting point for much of the work described in this article is the idea that quinone methides (QMs) are the electrophilic species that are generated from ortho-hydro-xybenzyl halides during the relatively selective modification of tryptophan residues in proteins. Therefore, a series of suicide substrates (a subtype of mechanism-based inhibitors) that produce quinone or quinonimine methides (QIMs) have been designed to inhibit enzymes. The concept of mechanism-based inhibitors was very appealing and has been widely applied. The present review will be focused on the inhibition of mammalian serine proteases and bacterial serine (3-lactamases by suicide inhibitors. These very different classes of enzymes have however an analogous step in their catalytic mechanism, the formation of an acyl-enzyme intermediate. Several studies have examined the possible use of quinone or quinonimine methides as the latent... 

Reduction of 3-benzyl-8-chloro-4-oxo-4//-pyrido[l,2- ]pyrimidine-2-carboxylate <2004W004/064741> and 2-methyl-4-oxo-4//-pyrido[l,2-tf]pyrimidine-3-carboxylate <2003T4123> with DIBAL-H afforded 2- and 3-formyl derivatives, respectively. Reduction of /V-(4-fluorobenzyl)-3-hydroxy-8-[methoxy(methyl)amino]-4-oxo-6,7,8,9-tetra-hydro-4//-pyrido[l,2- ]pyrimidine-2-carboxamide with Zn-dust in aqueous AcOH afforded the 8-methylamino derivative, which was acylated with AcOH in the presence of Hiinig s base, HOBt, and l-(3-dimethylaminopro-pyl)-3-ethylcarbodiimide-HCl <2004W004/058756>. 3-(Perhydropyrido[l,2- ]pyrimidin-2-yl)propylamine was obtained by catalytic hydrogenation of 2-(perhydropyrido[l,2- ]pyrimidin-2-yl)propionitrile over a Pt02 catalyst <2003FRP1275647>. 

The first disclosed natural product was cerulenin (15), an irreversible inhibitor of FabB. This hydrophobic epoxide locates itself in the hydro-phobic groove of the acyl site and reacts covalently with the active site cysteine [26]. However, 15 was also found to inhibit eukaryotic fatty acid synthase. 

Yang et al reeently reported on the meehanism of 4-chlorobenzoyl eoenzyme A dehalogenase, an enzyme that catalyzes the hydrolytic dehalogenation of 4-chlo-robenzoyl coenzyme A (4-CBA-CoA) to form 4-hydro-xybenzoyl coenzyme A (4-HBA-CoA). The mechanism involves attack of an active site carboxylate at C4 of the substrate benzoyl ring to form a Meisenheimer complex (shown above). Loss of chloride ion from this intermediate then forms an arylated enzyme intermediate that is hydrolyzed to free enzyme plus 4-HBA-CoA by the addition of water at the acyl carbon. In later work, Taylor et al examined the activation of the 4-CB A-CoA toward nucleophilic attack by the active site carboxylate group. 

In 1992, Sakai provided the first examples of highly enantioselective (>80% ee) hydro-acylations of olefins with aldehydes, the Rh(l)/BlNAP-catalyzed cyclization of 4-aUce-nals (Eq. 12) [14]. Additional work from the same laboratory established that certain 4-aryl-substituted substrates also undergo ring formation with good enantioselectivity... 

The presence of 4e as the predominant species during the catalysis is also in accord with the observed kinetic behavior of this catalyst with 1-octene and styrene as the substrates. The observation of this saturated acyl rhodium complex is in line with the positive dependence of the reaction rate on the hydrogen concentration and the zero order in alkene concentration. It was concluded previously that this saturated acyl complex is an unreactive resting state [18]. Before the final hydro-genolysis reaction step can occur, a CO molecule has to dissociate in order to form... 

Esters of A - hydro x y s u c c i n i in i d c are also used to carry out chemical modification of peptides, proteins, and other biological molecules by acylation of nucleophilic groups in these molecules. For example, detection of estradiol antibodies can be accomplished using... 

Benzofuranyl)butanoic acid readily forms the acid chloride, and this undergoes intramolecular Friedel-Crafts acylation on treatment with tin(IV) chloride in carbon disulfide at room temperature, providing 1,2,3,4-tetra-hydro-l-dibenzofuranone (54%). " This intermediate has been converted to dibenzofuran by lithium aluminum hydride reduction and subsequent dehydrogenation, to 1-methyldibenzofuran by Grignard reaction and dehydrogenation, and to 1-dibenzofuranol by reaction with iV-bromosuccinimide and subsequent dehydrobromination with pyridine. 

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