Alberto Casolari

Comparative studies of the influence of cyclodextrins on the stability of the sunscreen agent, 2-ethylhexyl-p-methoxycinnamate.

The effects of beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the base-catalyzed degradation and light-induced decomposition of the sunscreen agent, trans-2-ethylhexyl-p-methoxycinnamate (trans-EHMC) were investigated. Reversed-phase liquid chromatography was used to study the interaction between natural and modified cyclodextrins, added to the mobile phase, and the sunscreen. Among the available cyclodextrins (beta-CD, HP-beta-CD, hydroxypropyl-alpha-cyclodextrin and hydroxypropyl-gamma-cyclodextrin), only HP-beta-CD and beta-CD produced a significant decrease in the chromatographic retention of trans-EHMC. The complexation of the sunscreen agent with HP-beta-CD and beta-CD was confirmed by thermal analysis and nuclear magnetic resonance spectroscopy. beta-CD depressed the decomposition of trans-EHMC in alkaline solutions more effectively than HP-beta-CD. Moreover, the irradiation-induced degradation of the sunscreen agent in emulsion vehicles was reduced by complexation with beta-CD (the extent of degradation was 26.1% for the complex compared to 35.8% for free trans-EHMC) whereas HP-beta-CD had no significant effect. Therefore, the complex of beta-CD with trans-EHMC enhances the chemical- and photo-stability of the sunscreen agent. Moreover, it limits adverse interactions of the UV filter with other formulation ingredients.

Inclusion complexation of the sunscreen agent 2-ethylhexyl-p-dimethylaminobenzoate with hydroxypropyl-β-cyclodextrin: Effect on photostability

The interaction between the UV filter, 2‐ethylhexyl‐p‐dimethylaminobenzoate, and unmodified and modified α‐, β‐ or γ‐cyclodextrins was studied in water by phase‐solubility analysis.

Tandem michael reactions for the construction of pyrrolidine and piperidine ring systems

Abstract A convergent one-pot construction of disubstituted pyrrolidine and piperidine frameworks has been accomplished through a simple protocol involving intermolecular conjugate addition of a nitrogen nucleophile to an electrophilic olefin followed by intramolecular trapping of the generated enolate by a built-in α,β,-unsaturated acceptor.

Enantioselective synthesis of (+)- and (−)-α-allokainic acid

Abstract A concise enantioselective route to (+)- and (−)-a-allokainic acid from D- and L-serine respectively has been established by enantio- and diastereo-selective tandem Michael reaction methodology for the construction of three chiral centers in a single stage.

A convenient synthesis of λ-oxo-acrylates

Ethyl 2,4-dioxoalkanoates react chemoselectively with pyrrolidine acetate at the more electrophilic C-2 carbonyl, producing enaminone esters which on reduction with NaCNBH4 followed by pyrrolidine elimination, were transformed into γ-oxo-acrylates.

Effect of complexation with randomly methylated β-cyclodextrin on the aqueous solubility, photostability and antioxidant activity of an indolinonic nitroxide radical

The interaction between the hydrophobic indolinonic nitroxide radical, 1,2-dihydro-2-methyl-2-phenyl-3H-indole-3-one-1-oxyl and hydrophilic α-, β- and γ-cyclodextrin derivatives was investigated in water by phase-solubility analysis. Among the studied cyclodextrins, random methyl-β-cyclodextrin (RM-β-CD) had the greatest solubilizing activity (1312-fold increase in the intrinsic aqueous solubility). Solid complexes were prepared by the freeze-drying method and characterized by powder X-ray diffractometry and thermal analysis. Complexation of the nitroxide with RM-β-CD was also confirmed in solution by electron paramagnetic resonance (EPR) spectroscopy. Photodegradation of the nitroxide was reduced by complexation with RM-β-CD, this effect being more pronounced in the solid-state (the extent of degradation was 28.0% for the complex vs. 78.8% for uncomplexed nitroxide) than in solution (41.2 vs. 69.1% for uncomplexed nitroxide). The antioxidant activity of the complex was also investigated on the peroxidation of methyl linoleate micelles and on protein oxidation induced by free radical generators, and in both systems the free form of the nitroxide as well as its complex with RM-β-CD, showed essentially the same degree of protection. Moreover, EPR experiments showed a time-dependent decrease in the EPR signal of both the complexed and uncomplexed nitroxides with the free-radical generators. Therefore, RM-β-CD complexation of the nitroxide represents an effective strategy to improve its aqueous solubility and photostability, which is essential for certain biological applications, while it does not interfere with its radical scavenging efficiency.

Formal synthesis of (±)-Ambrox®

Abstract The immediate precursor of (±)-Ambrox®1 has been conveniently prepared in a seven-step sequence starting from the readily available methyl 2-oxo-5,5,8a-trimethyldecahydronaphthalene-1-carboxylate 2, in turn derived by stannic chloride-mediated cyclization of methyl 3-oxo-5-(2,6,6-trimethylcyclohexen-1-yl)pentanoate.

3,4-Bismethylenecyclopentanone ethylene ketal: A useful diene for[6.5]ring systems: Application to a formal synthesis of gibberellic acid

Abstract A convenient preparation of 3,4-bismethylenecyclopentanone ethylene ketal, a new valuable diene for Diels-Alder reaction, designed to produce functionalized [6.5] ring systems, is described. A formal synthesis of gibberellic acd GA3 using as starting materials two cycloadducts derived from the title compound demonstrates the value and the applicability of this methodology for the construction of functionalized hydrindane systems.

Isoxazoles-mediated synthesis of geiparvarin and dihydrogeiparvarin

Abstract A new synthesis of geiparvarin 1 and its dihydroderivative 2 two naturally occurring antitumor agents, possessing the 3(2H)-furanone ring system central structural feature, is described. The synthetic design is based on the use of suitably substituted isoxazole derivatives, the heterocyclic ring acting as masked 1,3-diketone moiety.

Enantioselective synthesis of the hexahydronaphthalene nucleus of (-)-compactin from ethyl (1R,2S)-2-methyl-4-oxocyclohexanecarboxylate and 2-(3-nitropropyl)-1,3-dioxolane as four carbon bifunctional annelating agent

Abstract An enantioselective approach to the synthesis of the hexahydronaphthalene nucleus of natural compactin is described. The key elements of the synthesis are as follows: (i) the preparation of the chiral starting material through enzymatic resolution of the readily available cis 2-methyl-4-oxocyclohexane carboxylic acid, (ii) conversion into the suitably protected (4S,5S)4-hydroxymethyl-5-methyl-2-cyclohexen-2-one by regioselective introduction of the α,β-carbon-carbon double bond by Pd(II)-catalyzed dehydrosilylation, (iii) construction of the new six-membered ring into the preexisting carbon skeleton using 2-(3-nitropropyl)-1,3-dioxolane as a four carbon bifunctional annelating reagent (iv) elaboration of the derived hexahydronaphthalenone to an advanced precursor already taken to the natural target by functional group manipulation, including conversion of the nitro group to the oxygenated function at C-1 and dehydration of an allylic alcohol to the required 1,3-diene moiety.