Paolo Linda

Aromaticity of Heterocycles

Publisher Summary This chapter discusses aromaticity of heterocycles. At a time when the validity of the concept of aromaticity is questioned, increasingly, it seems appropriate to review various definitions in common use and to survey their applications in heterocyclic chemistry. From a qualitative viewpoint the characteristics of an aromatic compound are easy to define. A compound is said to be aromatic if it is cyclic and unsaturated with an enhanced stability over simple olefinic compounds. The characteristic aromatic reactivity of the type described is clearly a matter of degree and is difficult to assess quantitatively. From a simple consideration of pyridine, which reacts less readily with electrophiles but more readily with nucleophiles at the ring carbon atoms than does benzene, it soon becomes apparent that attempts to discuss even relative aromatic character using kinetic criteria is fraught with difficulties; this is apart from the fundamental objection that chemical reactivity is not solely a function of ground-state stability.

Stability and activity of immobilised penicillin G amidase in ionic liquids at controlled aw

Despite the great interest in ionic liquids as novel solvents for biocatalysis, there is still no clear idea of their influence on the stability and the activity of enzymes. Here we analysed the activity and stability of PGA in six different ionic liquids, having different cations ([bmim] and [omim]) and anions (CH3OSO3−, PF6− and BF4−). To be active in ionic liquids, PGA-450 requires an acceptable hydration (aw > 0.60), as in organic solvents. PGA is highly stable in [bmim][PF6] and [bmim][BF4], and catalytic activity, assayed by studying the synthesis of the amide of L-phenylglycine methyl ester with methyl phenylacetate, in these ILS is comparable to that obtained in toluene.

d-Phenylglycine and d-4-hydroxyphenylglycine methyl esters via penicillin G acylase catalysed resolution in organic solvents

Abstract Penicillin G acylase in organic solvents catalyses specifically the acylation of the l -enantiomers of methyl esters of phenylglycine and 4-hydroxyphenylglycine. Hydrolytic reactions are prevented by controlling the water activity of the system and no excess of acylating agent is required. The process leads to the facile isolation of the enantiomerically pure d -enantiomer, which is of practical use for the preparation of β-lactam antibiotics. Electrospray mass spectroscopy has been applied to the study of the enantioselectivity of the enzyme.

CONTROL OF ENZYME HYDRATION IN PENICILLIN AMIDASE CATALYSED SYNTHESIS OF AMIDE BOND

Penicillin amidase catalyses the synthesis of amide bond in very high yield (>98%), using equimolar concentrations of the amine and the phenylacetic components. In situ hydrated phosphates were employed for controlling the water activity in a benzene/water system (97:3 v/v), where the water is taken up by the salt with formation of the hydrated species.

Relative reactivities of some furan and thiophene derivatives in the iodine- and tin tetrachloride-catalysed acetylations with acetic anhydride in dichloroethane☆

Abstract The reactivities of furan and thiophene in the catalysed acetylation by acetic anhydride, have been compared using a competitive procedure. Furan is more reactive than thiophene by a factor 9·3 or 11·9 according to the catalyst used (iodine or tin tetrachloride, respectively). This appears to be the first quantitative comparison of the reactivities of these two heterocyclic rings in an electrophilic substitution in which a proton is displaced. The rates of acetylation of 2-methylthiophene, 2-chlorothiophene and anisole relative to thiophene have been also determined and discussed.

Penicillin G amidase in low-water media: immobilisation and control of water activity by means of celite rods

Abstract Penicillin G amidase (PGA) adsorbed on Celite rods (Celite R-640 from Fluka) catalyses, in toluene, the synthesis of amide bonds with yields >98% using equimolar concentrations of reactants. The method allows the easy recovery of the product and the recycling of the catalyst. Experimental data have pointed out that Celite rods adsorb water in a unusual but useful way, maintaining the water activity of the reaction system constant within defined ranges of water concentrations. Adsorption isotherms of Celite rods are reported and further applications of the method are proposed.

Organically modified xerogels as novel tailor-made supports for covalent immobilisation of enzymes (penicillin G acylase)

Abstract A novel application of organically modified silicates for covalent immobilisation of penicillin G acylase is reported. The immobilisation is efficient and the enzymatic preparation shows high specific activity and thermal stability. The technique opens new perspectives for the preparation of innovative tailor-made supports matching specific requirements of enzymatic processes.

Activity of covalently immobilised PGA in water miscible solvents at controlled aw

Covalently immobilised penicillin G acylase is active in both apolar and water miscible solvents. Hydrated Celite R-640 added to water miscible solvents prevents the medium from stripping the water off the enzyme. The porous siliceous matrix has been used also for the dehydration and storage of the enzyme in apolar media.

Improved lipase-mediated resolution of mandelic acid esters by multivariate investigation of experimental factors

Abstract Lipase catalyzed stereoselective acylation of butyl mandelate was studied. The determining role of solvent and acylating agent was pointed out and a considerable inhibitory effect due to mandelic acid was observed by screening different lipases. Finally, the performance of the reaction was appreciably improved thank to a multivariate approach.

Activity of immobilised penicillin amidase in toluene at controlled water activity

Abstract Penicillin amidase (EC 3.5.1.11) supported on hydrated celite rods was used at constant water activity in toluene for the synthesis of amide bond. This approach couples the advantages coming from the immobilisation of the catalyst and the control of water activity in synthetic biotransformations, providing penicillin amidase with the water necessary for maintaining the catalytic activity. Furthermore, the thermodynamic equilibrium is shifted toward synthesis so that no competitive hydrolytic reaction occurs. The supported catalyst preserves its activity also after recycling. These features make the biocatalytic system of practical applicability in organic synthesis.