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Anticipating some thematic cores which would have occupied his reflection in the following years, Husserl examines the correlation between Nature and Spirit: a relationship which is not to be intended as an index of unidirectionality but, on the contrary, of mutual necessity. The fenomenological research assumes the burden of rediscovering the essential unity of both spheres by tapping into that precise horizon of sense which was forgotten by the specialist sciences producing, in this way, some burdensome misunderstandings: the reign of primeval evidences (Lebenswelt), which is taken as the central theme by the eidetic radical science which establishes and positions, with great epistemological scrupulousness and with high methodical rigor, all of possible sciences.

Synthesis of enantiomerically pure 7- and 8-hydroxystearic acids1 (7- and 8-HSA) has been accomplished starting from chiral non racemic 1-pentadecen-4-ol 1a and 1- tetradecen-4-ol 1b respectively, in accordance with the retrosynthetic procedure depicted in the Scheme. Access to enantiomerically pure homoallylic alcohols 1a,b was possible via kinetic resolution of the corresponding racemic acetates, catalyzed by Novozym 435 (Lipase B from Candida antarctica). Yamaguchi esterification2 of 1a,b with 4-pentenoic and 5-hexenoic acids 2a,b respectively afforded the suitable dienic esters 3a,b which were submitted to Ring- Closing Metathesis Reaction (RCM).3 Hydrogenation of the resulting complex reaction mixtures followed by hydrolysis under basic conditions afforded the expected chiral non racemic 7- and 8-HSA in about 40% total yield. Scheme

Both enantiomers of three biologically relevant paraconic acids—MB-3, methylenolactocin, and C75—were obtained with enantioselectivities up to 99% by kinetic enzymatic resolutions. Good enantiomeric excesses were obtained for MB-3 and methylenolactocin, using α-chymotrypsin and aminoacylase as enantiocomplementary enzymes, while C75 was resolved with aminoacylase. They all were evaluated for their antiproliferative, antibacterial, and antifungal activities, showing weak effects and practically no difference between enantiomers in each case. At high concentrations (16–64 μg/mL), (–)- C75 acted as an antimicrobial agent against Gram-positive bacteria.

Amanita fungi are the main lethal toadstool among the 1000 poisonous mushrooms known in the world. Thrombin is the key serine proteinase of the coagulation cascade and therefore a suitable target for inhibition of blood coagulation. An extract of Amanita virosa considerably inhibited thrombin (48%) and showed no inhibitory activity on trypsin. On the basis of inhibition selectivity between thrombin and trypsin and potency of thrombin inhibition, Amanita virosa constituted a good starting material for isolation of further compounds that are active against thrombin. In a preliminary study, 95 selected mushroom species have been screened in order to find novel specific non-peptidic thrombin inhibitors. The extract of Amanita virosa considerably inhibited thrombin (48% at concentration of 120 μg/mL). A bioassay oriented fractionation of the extract of Amanita virosa has led to the isolation of active compounds. On the basis of spectroscopic data, chemical reactions and GCMS analysis, complex mixtures of triglycerides, monoacylglycerols, free fatty acids and ergosterol have been isolated and identified.

Photodynamic therapy (PDT) is a non-invasive therapeutic modality used in a various number of diseases and cancer. It involves the systemic or topic administration of a photosensitizer, followed by irradiation with light. The activated photosensitizer converts oxygen to singlet oxygen and/or reactive oxygen species (ROS) which lead to cell death and tissue necrosis. One aim of PDT research is the discovery of new photosensitizers possessing minimal dark cytotoxicity, high photodynamic properties, improved pharmacokinetics, preferential retention in diseased instead of healthy tissues, chemical stability and a good cellular uptake .We recently focused our efforts on pheophorbide a (Pba), a chlorophyll derivative. Pba is characterized by a stronger absorption between 650-700 nm, in the tissuepenetrating wavelength range. For in vivo applications the capacity of the photosensitiser to reach in the diseased tissues becomes critical, in particular when a large peritoneal area is interested as occurring in carcinomatosis and sarcomatosis. To improve the pharmacokinetic and the activity of the photosensitizer we conjugated Pba to polyethylene glycol (PEG). In vivo the pharmacokinetic analysis performed on living female C57/BL6 mice bearing a subcutaneous melanoma mass, showed that injected mPEG-Pba distributes all over the body, with an higher uptake in the tumor respect to free Pba. Moreover, preliminary data suggest that PEG-Pba in mice bearing B78-H1 amelanotic melanoma reduces the tumor growth after light activation in comparison with Pba.

Enantiomerically pure 4-methyl-tetrahydro-5-oxo-2-furancarboxylic acids and esters are prepared by enzymatic resolution of the chiral racemic esters. Their stereochemistry as well as their absolute configurations have been established by chemical correlation. The influence of the alkoxycarbonyl group at C-2 and that of the methyl group at C-4 on the sign of the Cotton effect in their CD spectra have been investigated. Formation of enantiomerically pure hydroxydiesters, precursors of the above-mentioned gamma-lactones, by baker's yeast reduction of the corresponding ketodiesters was unsatisfactory.

1997/1998 XI Ciclo 1968 Versione digitalizzata della tesi di dottorato cartacea.