Carlo F. Morelli

Tin (IV) Chloride-promoted Synthesis of 4-Aminopyridines and 4-Aminoquinolines

Abstract Ortho-aminobenzonitriles 1 react with β-ketoesters and alkyl malonates, in the presence of stoichiometric amounts of tin(IV) chloride, to give 4-aminoquinolines 2 and 4-amino-2-quinolones 3 respectively. Similarly β-enaminonitriles 7 afford 4-aminopyridines 8 and 4-amino-2-pyridones 9.

Characterisation of mucilages extracted from seven Italian cultivars of flax

The chemical composition, physicochemical, functional and sensory properties of mucilages, extracted from seven Italian flax cultivars, were evaluated. All samples were composed of neutral and acidic sugars, with a low protein content. From the NMR data, a rhamnogalacturonan backbone could be inferred as a common structural feature for all the mucilages, with some variations depending on the cultivar. All the suspensions showed a poor stability, which was consistent with a low zeta potential absolute value. The viscosity seemed to be positively correlated with the neutral sugars and negatively with the amount of proteins. Functional properties were dependent on the cultivar. The sensory analysis showed that most mucilages are tasteless. All these outcomes could support the use of flaxseed mucilages for industrial applications. In particular, Solal and Festival cultivars could be useful as thickeners, due to their high viscosity, while Natural, Valoal and Kaolin as emulsifiers for their good surface-active properties.

A facile synthesis of pyrazole, isoxazole and pyrimidine ortho-dicarboxylic acid derivatives via β-enaminoketoesters

Abstract β-Alkoxycarbonyl-β-enaminoketoesters 1a,b react with hydrazines to give pyrazole ortho -dicarboxylic acid derivatives 3, 4 and 5 . Similarly 1a reacts with hydroxylamine to give isoxazole 6 and with amidines and guanidine to give pyrimidine ortho -dicarboxylic acid monoesters 7a-c . The total or partial hydrolysis of selected heterocycles afforded the dicarboxylic acids 8, 9 and 10 and the dicarboxylic acid monoesters 11 and 12 .

pH-Dependent hydrolase, glutaminase, transpeptidase and autotranspeptidase activities of Bacillus subtilis γ-glutamyltransferase

γ‐Glutamyltransferases (γ‐GTs) are heterodimeric enzymes that catalyze the transfer of a γ‐glutamyl group from a donor species to an acceptor molecule in a transpeptidation reaction through the formation of an intermediate γ‐glutamyl enzyme. In our search for a γ‐GT from a generally recognized as safe microorganism suitable for the production of γ‐glutamyl derivatives with flavor‐enhancing properties intended for human use, we cloned and overexpressed the γ‐GT from Bacillus subtilis. In this study, we report the behavior of B. subtilis γ‐GT in reactions involving glutamine as the donor compound and various acceptor amino acids. The common thread emerging from our results is a strong dependence of the hydrolase, transpeptidase and autotranspeptidase activities of B. subtilis γ‐GT on pH, also in relation to the pKa of the acceptor amino acids. Glutamine, commonly referred to as a poor acceptor molecule, undergoes rapid autotranspeptidation at elevated pH, affording oligomeric species, in which up to four γ‐glutamyl moieties are linked to a single glutamine. Moreover, we found that d‐glutamine is also recognized both as a donor and as an acceptor substrate. Our results prove that the B. subtilis γ‐GT‐catalyzed transpeptidation reaction is feasible, and the observed activities of γ‐GT from B. subtilis could be interpreted in relation to the known ability of the enzyme to process the polymeric material γ‐polyglutamic acid.

A new route to the synthesis of pyrazole and pyrimidine C-nucleoside derivatives

Abstract A new route to the synthesis of pyrazole and pyrimidine C-nucleosides, which involves as the key step a metal promoted reaction of β-D-ribofuranosyl ketoesters with alkyl cyanoformates is described. 2,3,5-Tri-O-benzoyl-β-D-ribofuranosyl cyanide 1 reacts with α-bromoesters, in the presence of zinc dust, to give β-D-ribofuranosyl-enaminoesters 2 which are hydrolysed with 1N hydrochloric acid to β-ketoesters 3. The reactions of β-ketoesters 3 with alkyl cyanoformates, in the presence of tin(IV) chloride or of catalytic amounts of metal acetylacetonates, afford β-D-ribofuranosyl enaminoketoesters 4. These compounds react with benzylhydrazine and acetamidine to give pyrazole and pyrimidine C-nucleosides (6,7).

A new and efficient route to the synthesis of pyrazole and pyrimidine C-nucleoside derivatives

Abstract A new route to the synthesis of pyrazole and pyrimidine C-nucleosides, involving as the key step a metal catalysed reaction of β-D-ribofuranosyl ketoesters with alkyl cyanoformates, is described, 2,3,5-Tri-O-benzoyl-β-D-ribofuranosyl cyanide (1) reacts with α-bromoesters, in the presence of zinc dust, to give β-D-ribofuranosyl-enaminoesters 2 which are easily hydrolised to β-ketoesters 3. The reactions of compounds 3 with alkyl cyanoformates, in the presence of catalytic amounts of [Cu(acac)2], afford C-glycosyl enaminoketosters 4. These compounds react with benzylhydrazine and acetamidine to give pyrazole and pyrimidine C-nucleosides 5 and 6 respectively.

Generation and cycloaddition reactions of substituted 2-nitro-1,3-dienes

Abstract 4-Acyloxy-2-substituted-3-nitro-1-butenes have been utilized as convenient precursors of the corresponding 2-nitro-3-substituted-1,3-butadienes which could be easily generated in situ by heating or by treatment with sodium acetate and trapped by suitable partners such as methyl acrylate, cyclopentadiene or ethyl vinyl ether. The expected cycloadducts are regiochemically formed by reaction with methyl acrylate, while the initially formed adducts with cyclopentadiene underwent thermal Cope or hetero-Cope rearrangements leading to the formation of nitro-substituted bicyclic compounds. The thermal rearrangement of the oxazine-N-oxides resulting through hetero Diels-Alder reaction with ethyl vinyl ether as cycloaddition partner led to the formation of 1,2-oxazole-3-propionaldehydes. The wide variety of highly functionalized carbocyclic and heterocyclic compounds generated through the use of these multi-coupling reagents provided useful synthons for the construction of simple and complex natural compounds.

Chemoenzymatic synthesis of neoglycoproteins driven by the assessment of protein surface reactivity

In this paper a series of 2-iminomethoxyethyl mannose-based mono- and disaccharides have been synthesized by a chemoenzymatic approach and used in coupling reactions with e-amino groups of lysine residues in a model protein (ribonuclease A, RNase A) to give semisynthetic neoglycoconjugates. In order to study the influence of structure of the glycans on the conjugation outcomes, an accurate characterization of the prepared neoglycoproteins was performed by a combination of ESI-MS and LC-MS analytical methods. The analyses of the chymotryptic digests of the all neoglycoconjugates revealed six Lys-glycosylation sites with a the following order of lysine reactivity: Lys 1 ≫ Lys 91 ≅ Lys 31 > Lys 61 ≅ Lys 66. A computational analysis of the reactivity of each lysine residue has been also carried out considering several parameters (amino acids surface exposure and pKa, protein flexibility). The in silico evaluation seems to confirm the order in lysine reactivity resulting from proteomic analysis.

Mechanism of anaerobic ether cleavage: conversion of 2-phenoxyethanol to phenol and acetaldehyde by Acetobacterium sp.

2-Phenoxyethanol is converted into phenol and acetate by a strictly anaerobic Gram-positive bacterium,Acetobacterium strain LuPhet1. Acetate results from oxidation of acetaldehyde that is the early product of the biodegradation process (Frings, J., and Schink, B. (1994) Arch. Microbiol. 162, 199–204). Feeding experiments with resting cell suspensions and 2-phenoxyethanol bearing two deuterium atoms at either carbon of the glycolic moiety as substrate demonstrated that the carbonyl group of the acetate derives from the alcoholic function and the methyl group derives from the adjacent carbon. A concomitant migration of a deuterium atom from C-1 to C-2 was observed. These findings were confirmed by NMR analysis of the acetate obtained by fermentation of 2-phenoxy-[2-13C,1-2H2]ethanol, 2-phenoxy-[1-13C,1-2H2]ethanol, and 2-phenoxy-[1,2-13C2,1-2H2]ethanol. During the course of the biotransformation process, the molecular integrity of the glycolic unit was completely retained, no loss of the migrating deuterium occurred by exchange with the medium, and the 1,2-deuterium shift was intramolecular. A diol dehydratase-like mechanism could explain the enzymatic cleavage of the ether bond of 2-phenoxyethanol, provided that an intramolecular H/OC6H5 exchange is assumed, giving rise to the hemiacetal precursor of acetaldehyde. However, an alternative mechanism is proposed that is supported by the well recognized propensity of α-hydroxyradical and of its conjugate base (ketyl anion) to eliminate a β-positioned leaving group.

Regio- and diastereoselectivity in TiCl4-promoted reduction of 2-aryl-substituted cis-4-methyl-5-trifluoromethyl-1,3-dioxolanes

Abstract TiCl 4 -mediated reduction of both syn - and anti -(4 S ,5 S )-2-aryl-4-methyl-5-trifluoromethyl-1,3-dioxolanes with Et 3 SiD furnished monodeuterated hydroxy ethers resulting from the same regio- and stereoselective CO bond cleavage (yields >80%; 82–92% de). Deuteride addition to the benzylidene acetal and removal of the alkyl moiety from the reaction product gave ( R )-(α- 2 H)benzyl alcohol (90% ee), thus suggesting a new route to chiral 1-deuteriobenzyl alcohols. A mechanistic rationale is proposed and supported by theoretical calculations.