Bruno Danieli

Regioselective acylation of polyhydroxylated natural compounds catalyzed by Candida Antarctica lipase B (Novozym 435) in organic solvents

Abstract A systematic investigation on the transesterification activity and regioselectivity of the immobilized lipase B from Candida antarctica (Novozym 435) has been performed. This enzyme has been found to be quite active in such solvents as THF, acetone, dioxane, and in mixtures of these solvents with pyridine. Several glycopyranosides have been acetylated, showing that the regioselectivity displayed by Novozym 435 towards sugar secondary OHs is deeply influenced by the nature of the aglycone and by the stereochemistry of the glycosidic bond. This information on the regioselectivity of the lipase has been exploited for the preparation of acetyl derivatives of flavonoid glycosides.

Enzymatic synthesis of various 1′-O-sucrose and 1-O-fructose esters

A crude preparation of the proteolytic enzyme subtilisin has been used to catalyse the regioselective esterification of sucrose in anhydrous dimethylformamide. In this way 1′-O-sucrose esters bearing acyl groups of different sizes and types have been synthesized. These sucrose derivatives have been hydrolysed by yeast α-glucosidase to the corresponding 1-O-fructose esters, not easily attainable by chemical methods.

Selective laccase-mediated oxidation of sugars derivatives

A laccase from Trametes pubescens and the chemical mediator TEMPO have been used to catalyze the regioselective oxidation of the primary hydroxyl groups of sugar derivatives. The efficiency of this system has been initially tested with mono- and disaccharides (i.e., phenyl β-D-glucopyranoside), and the corresponding glycopyranosiduronates have been isolated and characterized. Subsequently, this chemo-enzymatic approach has been exploited to achieve the partial oxidation of a water soluble cellulose sample.

Inhibitors of tubulin polymerization: synthesis and biological evaluation of hybrids of vindoline, anhydrovinblastine and vinorelbine with thiocolchicine, podophyllotoxin and baccatin III.

A series of novel hybrid compounds obtained by the attachment of anhydrovinblastine, vinorelbine, and vindoline to thiocolchicine, podophyllotoxin, and baccatin III are described. Two types of diacyl spacers are introduced. The influence of the hybrid compounds on tubulin polymerization is reported. The results highlight the importance of the length of the spacer. Immunofluorescence microscopy and flow cytometry measurements that compound with the best in vitro activity could disrupt microtubule networks in cell and prevent the formation of the proper spindle apparatus, thereby causing cell cycle arrest in the G2/M phase. The newly synthesized compounds were tested in the human lung cancer cell line A549.

Synthesis and evaluation of C-seco paclitaxel analogues☆

Abstract Starting from 7,9-diTes-10-dehydro C- seco baccatin III ( 4a ), C- seco analogues of paclitaxel retaining biological activity were synthesised.

Synthesis and biological evaluation of novel thiocolchicine–podophyllotoxin conjugates

The synthesis and biological evaluation of 9 dimeric compounds obtained by condensation of thiocolchicine and/or podophyllotoxin with 6 different dicarboxylic acids is described. In particular, tubulin assembly assay and immunofluorescence analysis results are reported. The biological data highlighted three compounds as being more active than the others, having a marked ability to inhibit the polymerization of tubulin in vitro and causing significant disruption to the microtubule network in vivo. The spacer unit was found to have a significant effect on biological activity, reinforcing the importance of the design of conjugate compounds to create new biologically active molecules in which the spacer could be useful to improve the solubility and to modulate the efficacy of well known anticancer drugs.

Minor diterpenoids of Coleus forskohlii

The structures of four diterpenoids, isolated from the roots of Coleus forskohlii, have been elucidated as 7β-acetoxy-6β,9α-dihydroxy-8,13-epoxy-labd-14-en-11-one (7), 6β,7β,9α-trihydroxy-8,13-epoxy-labd-14-en-11-one (8), 6β-hydroxy-8,13-epoxy-labd-14-en-11-one (9), 8,13-epoxy-labd-14-en-11-one (10) by spectral analysis in comparison with forskolin (1) and its congeners.

First asymmetric oxidation of tertiary amines by cyclohexanone monooxygenase

Abstract Cyclohexanone monooxygenase catalyzes the asymmetric oxidation of some tertiary amines to amine N -oxides. The structure of the amine markedly influences the enantiomeric excess of products.

Synthesis of enantiopure diamine ligands related to sparteine, via scandium triflate-catalyzed imino Diels–Alder reactions

Imino Diels–Alder reactions have been investigated as a new route to sparteine analogues. The first enantioselective synthesis of two diastereoisomeric tricyclic diamines, structurally equivalent to the ABC and BCD rings of the naturally occurring alkaloid, is reported, starting from enantiopure intermediates. The effectiveness of the diamines in the lithiation of N-Boc-pyrrolidine is discussed.

Application of the Pd-catalyzed heteroarylation to the synthesis of 5-(indol-2′-yl)pyridin-2-one and 5-(indol-2′-yl)pyran-2-one

Abstract The synthesis of 5-(indol-2′-yl)pyridin-2-ones and 5-(indol-2′-yl)pyran-2-one by Pd-catalyzed reactions is described. The best results are obtained using 2-indolylstannanes or 2-indolylzinc halides to be coupled with 5-bromopyridin-2-ones or 5-bromopyran-2-one in the presence of Pd(PPh3)4 as catalyst. Other Pd-catalyzed reactions are discussed.