Ronaldo Aloise Pilli

Novel Supramolecular Palladium Catalyst for the Asymmetric Reduction of Imines in Aqueous Media

A novel approach to the asymmetric reduction of dihydro-beta-carboline derivatives to the corresponding tetrahydro-beta-carbolines is described based on the supramolecular lyophilized complex formed from beta-cyclodextrin/imines as an enzyme mimetic and palladium hydride as the reducing agent. The methodology allowed us to develop a short and efficient preparation of (R)-harmicine and (R)-deplancheine alkaloids in high overall yields and ee of 89 and 90%, respectively.

Effect of goniothalamin on the development of Ehrlich solid tumor in mice

In this work the antiproliferative activity of goniothalamin (1), both in racemic and in its enantiomeric pure forms, in a solid tumor experimental model using laboratory animals is described. The antiedematogenic activity displayed by racemic 1 in the carrageenan edema model in mice together with the reduction of Ehrlich solid tumor model suggest a relationship between anticancer and antiinflammatory activities with the antiinflammatory activity favoring the antiproliferative activity itself.

Synthesis of 1-ferrocenyl-2-aryl(heteroaryl)acetylenes and 2-ferrocenylindole derivatives via the Sonogashira–Heck–Cassar reaction

Abstract The Sonogashira–Heck–Cassar reaction of ferrocenylacetylene with aryl- and heteroaryl halides was shown to be a facile and convenient route for the synthesis of 1-ferrocenyl-2-aryl- and 1-ferrocenyl-2-heteroarylacetylenes in high yields. Additionally, annulation reactions of some of the 1-ferrocenylacetylene compounds gave 2-ferrocenyl-2-benzo[ b ]furan and 2-ferrocenylindoles in good yields.

Enhanced trans diastereoselection in the allylation of cyclic chiral N-acyliminium ions. Synthesis of hydroxylated indolizidines

A short synthesis of hydroxylated indolizidines is reported. The key steps were the allylation of chiral cyclic N-acyliminium ions derived from malic and tartaric acids, followed by ring-closing metathesis.

Cytotoxicity of goniothalamin enantiomers in renal cancer cells: Involvement of nitric oxide, apoptosis and autophagy

Goniothalamin is a styryllactone synthesized by plants of the genus Goniothalamus. The biological activities of this molecule, particularly its anti-protozoan, anti-fungal, and larvicidal properties, have received considerable attention. In this work, we investigated the action of the natural and synthetic enantiomers (R)-goniothalamin (1) and (S)-goniothalamin (ent-1) on cell viability, nitric oxide synthase (NOS) expression and activity, and the expression of selected proteins involved in apoptosis and autophagy in renal cancer cells. Both compounds were cytotoxic and decreased the mitochondrial function of renal cancer cells. However, the enantiomers differentially affected the expression/activity profiles of some signaling pathway mediators. Ent-1 (4 nM) was more potent than 1 (6.4 microM) in inhibiting constitutive NOS activity (54% and 59% inhibition, respectively), and both enantiomers decreased the protein expression of neuronal and endothelial NOS, as assessed by western blotting. Ent-1 and 1 caused down-regulation of Ras and TNFR1 and inhibition of protein serine/threonine phosphatase 2A (PP2A). Compound 1 markedly down-regulated Bcl2, an anti-apoptotic protein, and also induced PARP cleavage. Despite inducing an expressive down-regulation of Bax, ent-1 was also able to induce PARP cleavage. These results suggest that these compounds caused apoptosis in renal cancer cells. Interestingly, ent-1 enhanced the expression of LC3, a typical marker of autophagy. NFkappaB was down-regulated in 1-treated cells. Overall, these results indicate that the anti-proliferative activity of the two enantiomers on renal cancer cells involved distinct signaling pathways, apoptosis and autophagy as dominant responses towards 1 and ent-1, respectively.

Total synthesis of (−)-decarestrictine D through a stereoselective intramolecular Nozaki-Hiyama-Kishi reaction

Abstract A concise total synthesis of (−)-decarestrictine D (1) from 1,3-propanediol and polyhydroxybutyrate (PHB) is described. The approach involves the stereoselective intramolecular Nozaki-Hiyama-Kishi coupling to construct the decanolide ring and to set the proper configuration at C-7.

Creation of quaternary stereocenters by the addition of allyltributyltin to chiral cyclic N-acyliminium ions

Abstract 5,5-Disubstituted pyrrolidinones and 5-substituted pyrrolidinones were obtained with moderate to good diastereoisomeric excess through the cis addition of allyltributyltin and triethylsilane, respectively, to the 4-OTBS group in the N-acyliminium ion prepared from the corresponding 5-hydroxy lactams. Cyclization of an N-allyl-5-propargyl pyrrolidinone and N-allyl-5-allyl-5-substituted pyrrolidinones using Grubbs’ catalyst led to the preparation of a dehydropyrrolizinone and dehydroindolizinones containing a quaternary stereocenter.

The addition of 2-tert-butyldimethylsilyloxyfuran to cyclic N-acyliminium ions containing cyclohexyl-based chiral auxiliaries

The vinylogous Mannich addition of silyloxyfuran 5 to chiral five- and six-membered N -acyliminium ions derived from 3 / 4a , b occurred exclusively through the addition to the N -acyliminium Si face to provide threo - 6 / 7a , b as the major isomer (73–84% yield, 2:1–7:1 diastereoisomeric ratio) which were converted to the corresponding bicyclic lactams 10 and 11 with efficient recovery of the chiral auxiliary.

The Stemona Alkaloids

Publisher Summary This chapter discusses the structural classification, synthesis, biological activity, and natural sources of stemona alkaloids. The Stemona alkaloids are structurally characterized by the presence of either an exposed or hidden pyrrolo[1,2-a]azepine (n=1) moiety, also named perhydroazaazulene or 4-aza-azulene, or a pyrido[1,2-a]azepine (n=2) nucleus and currently comprises 68 alkaloids. The biological activities of some Stemona alkaloids are evaluated in order to find the active principles of Stemona species. Tuberostemonine was the first Stemona alkaloid to have its biological activity tested. The anthelminthic activity of this alkaloid was detected against Angiostrongylus cantonensis, Dipylidium caninun, and Fasciola hepatica with an effect on the motility of these helminthic worms. Tuberostemonine was pointed out as the bioactive principle responsible for the insecticidal activity of S. tuberosa , with activity levels comparable to those of azadirachtin, after being tested against the larvae of Spodoptera littoralis . The action of tuberostemonine on the neuromuscular transmission in crayfish was also investigated, revealing that this alkaloid depressed glutamate-induced responses at similar concentrations of those of established glutamate inhibitors. The Stemonaceae is so far the only source of the Stemona alkaloids.

Synthesis of methoxylated goniothalamin, aza-goniothalamin and γ-pyrones and their in vitro evaluation against human cancer cells.

The present work describes the preparation of three novel series of compounds based on the structure of goniothalamin, a natural styryl lactone which has been found to display cytotoxic and antiproliferative activities against a variety of cancer cell lines. A focused library of 29 novel goniothalamin analogues was prepared and evaluated against seven human cancer cell lines. While the γ-pyrones and the aza-goniothalamin analogues were less potent than the lead compound, 2,4-dimethoxy analogue 88 has shown to be more potent in vitro than goniothalamin against all cancer cell lines evaluated. Furthermore, it was more potent than doxorubicin against NCI-ADR/RES, OVCAR-03 and HT-29 while being less toxic to human keratinocytes (HaCat). The 3,5-dimethoxy analogue 90 and 2,4,5-trimethoxy analogue 92 also displayed promising antiproliferative activity when compared to goniothalamin (1). These results provide new elements for the design and synthesis of novel representatives of this family of natural compounds.