Massimo Curini

Chemistry and biological activity of natural and synthetic prenyloxycoumarins.

Prenyloxycoumarins and prenyloxyfuranocoumarins (isopentenyloxy-, geranyloxy-, linear and cyclic sesquiterpenyloxy compounds and their biosynthetic derivatives) represent a family of secondary metabolites that have been considered for years just as intermediates of other coumarin-based compounds. Only in the last two decades these secondary metabolites have been recognized as interesting and valuable biologically active natural products. Up to now more than 160 compounds have been isolated from plants mainly belonging to the families of Rutaceae and Umbelliferae, comprising common edible vegetables and fruits like lemons, oranges and grapefruits. In view of the biological activity of some natural prenyloxycoumarins, very recently syntheses of structurally related analogs aimed to establish detailed structure-activity relationships have also been carried out. Many of the isolated prenyloxy- and prenyloxy-furanocoumarins and their semisynthetic derivatives were shown to exert in vitro and in vivo remarkable anti-tumoral, anti-inflammatory and anti-viral effects. The object of this review is to examine in detail the different types of prenyloxycoumarins and prenyloxyfuranocoumarins from the chemical, phytochemical and biological point of view.

Ytterbium triflate promoted synthesis of 1,5-benzodiazepine derivatives

Abstract 2,3-Dihydro-1 H -1,5 benzodiazepines have been synthetized in very good yield in solvent-free conditions from o -phenylendiamine and ketones in the presence of Yb(OTf) 3 as catalyst. The method is applicable to both cyclic or acyclic ketones without significant differences.

Layered zirconium phosphate and phosphonate as heterogeneous catalyst in the preparation of pyrroles

Abstract Pyrroles may be prepared by condensation of alkyl and aryl amines and 1,4-diketones (Paal–Knorr reaction) under potassium exchanged layered Zirconium phosphate and zirconium sulfophenyl phosphonate catalyst in solvent free conditions.

Heterogeneous Catalysis in Trimethylsilylation of Alcohols and Phenols by Zirconium Sulfophenyl Phosphonate

Abstract Layered zirconium sulfophenyl phosphonate was found to be an efficient heterogeneous catalyst for the trimethylsilylation of alcohols and phenols.

Dietary administration with prenyloxycoumarins, auraptene and collinin, inhibits colitis-related colon carcinogenesis in mice

We previously reported the chemopreventive ability of a prenyloxycoumarin auraptene in chemically induced carcinogenesis in digestive tract, liver and urinary bladder of rodents. The current study was designed to determine whether dietary feeding of auraptene and its related prenyloxycoumarin collinin can inhibit colitis‐related mouse colon carcinogenesis. The experimental diets, containing the compounds at 2 dose levels (0.01 and 0.05%), were fed for 17 weeks to male CD‐1 (ICR) mice that were initiated with a single intraperitoneal injection of azoxymethane (AOM, 10 mg/kg body weight) and promoted by 1% (w/v) DSS in drinking water for 7 days. Their tumor inhibitory effects were assessed at week 20 by counting the incidence and multiplicity of colonic neoplasms and the immunohistochemical expression of proliferating cell nuclear antigen (PCNA)‐labeling index, apoptotic index, cyclooxygenase (COX)‐2, inducible nitric oxide (iNOS) and nitrotyrosine in colonic epithelial malignancy. Feeding with auraptene or collinin, at both doses, significantly inhibited the occurrence of colonic adenocarcinoma. In addition, feeding with auraptene or collinin significantly lowered the positive rates of PCNA, COX‐2, iNOS and nitrotyrosine in adenocarcinomas, while the treatment increased the apoptotic index in colonic malignancies. Our findings may suggest that certain prenyloxycoumarins, such as auraptene and collinin, could serve as an effective agent against colitis‐related colon cancer development in rodents.

Preparation and deprotection of 1,1-diacetates (acylals) using zirconium sulfophenyl phosphonate as catalyst

Layered zirconium sulfophenyl phosphonate was found to be an efficient heterogeneous catalyst for the preparation and deprotection of 1,1-diacetates.

Carbamate synthesis from amines and dimethyl carbonate under ytterbium triflate catalysis

A facile synthesis of carbamates from amines and dimethyl carbonate has been achieved using ytterbium triflate as catalyst.

Zirconium Sulfophenyl Phosphonate as a Heterogeneous Catalyst in the Preparation of β-Amino Alcohols from Epoxides

A convenient method for the ring opening of epoxides by aromatic amines, catalysed by zirconium sulfophenyl phosphonate in solvent-free conditions, is described.

Colorectal cancer chemoprevention by 2 β-cyclodextrin inclusion compounds of auraptene and 4′-Geranyloxyferulic acid.

The inhibitory effects of novel prodrugs, inclusion complexes of 3‐(4′‐geranyloxy‐3′‐methoxyphenyl)‐2‐trans propenoic acid (GOFA) and auraptene (AUR) with β‐cyclodextrin (CD), on colon carcinogenesis were investigated using an azoxymethane (AOM)/dextran sodium sulfate (DSS) model. Male CD‐1 (ICR) mice initiated with a single intraperitoneal injection of AOM (10 mg/kg body weight) were promoted by the addition of 1.5% (w/v) DSS to their drinking water for 7 days. They were then given a basal diet containing 2 dose levels (100 and 500 ppm) of GOFA/β‐CD or AUR/β‐CD for 15 weeks. At Week 18, the development of colonic adenocarcinoma was significantly inhibited by feeding with GOFA/β‐CD at dose levels of 100 ppm (63% reduction in multiplicity, p < 0.05) and 500 ppm (83% reduction in the multiplicity, p < 0.001), when compared with the AOM/DSS group (multiplicity: 3.36 ± 3.34). In addition, feeding with 100 and 500 ppm (p < 0.01) of AUR/β‐CD suppressed the development of colonic adenocarcinomas. The dietary administration with GOFA/β‐CD and AUR/β‐CD inhibited colonic inflammation and also modulated proliferation, apoptosis and the expression of several proinflammatory cytokines, such as nuclear factor‐kappaB, tumor necrosis factor‐α, Stat3, NF‐E2‐related factor 2, interleukin (IL)‐6 and IL‐1β, which were induced in the adenocarcinomas. Our findings indicate that GOFA/β‐CD and AUR/β‐CD, especially GOFA/β‐CD, are therefore able to inhibit colitis‐related colon carcinogenesis by modulating inflammation, proliferation and the expression of proinflammatory cytokines in mice.

Synthesis of Collinin, an Antiviral Coumarin

Collinin (1), a geranyloxycoumarin, has been synthesized in three steps and 24.6% overall yield from pyrogallol (2) and propiolic acid (3).