Jean d’Angelo

Regioselective Annulation of 1,5-Diketones: Access to Functionalized Hagemann’s Esters

The synthesis of the “functionalized” Hagemann’s ester (S)-18 was investigated. The common starting material in these approaches was enamino ester (S,Z)-5, which was prepared through the condensation of keto diester 4 with (S)-1-phenylethylamine. The Michael addition reaction of 5 with methyl vinyl ketone gave the expected adduct (S)-6 with an ee ⩾ 95%. However, all attempts at annulation of 6 invariably afforded the unwanted cyclohexenone derivatives 7 or 8. The addition of 5 to Nazarov reagent 9 furnished adduct (S)-10 with an ee ⩾ 95%. The Triton B-induced annulation of 10 unexpectedly gave aldol 11. Depending on the reaction conditions, annulation of 11 afforded either the bicyclic lactone 12, or cyclohexenones 13 or 15. An efficient way of reversing the sense of the regiochemistry of the previous annulation was found, based on the use of diethyl 2-oxo-3-vinylphosphonate (16) as a Michael acceptor. Thus, the condensation of 5 with 16 gave (S)-17 with an ee ⩾ 95%, and cyclization of (S)-17 under Horner−Wadsworth−Emmons conditions gave the desired Hagemann’s ester (S)-18. The structural assignments for 18 were ascertained by chemical correlation with the known hydrindenedione (S)-21.

Antitumor activity of a rhenium (I)-diselenoether complex in experimental models of human breast cancer.

SummaryRhenium (I)-diselenother (Re-diselenoether) is a water soluble metal-based compound, combining one atom of rhenium and two atoms of selenium. This compound has been reported to exhibit marked activities against several solid tumor cell lines. We now disclose an improved synthesis of this complex. The Re-diselenoether showed a potent inhibitory effect on MDA-MB231 cell division in vitro, which lasted when the complex was no longer present in the culture. Re-diselenoether induced a remarkable reduction of the volume of the primitive breast tumors and of the pulmonary metastases without clinical signs of toxicity, in mice-bearing a MDA-MB231 Luc+ tumor, orthotopically transplanted, after a daily oral administration at the dose of 10xa0mg/kg/d. Interestingly, an antagonism was observed when cisplatin was administered as a single i.p. injection 1xa0week after the end of the Re-diselenoether administration. In an effort to gain insight of the mechanisms of action of Re-diselenoether complex, interaction with 9-methylguanine as a nucleic acid base model was studied. We have shown that Re-diselenoether gave both mono- and bis-guanine Re adducts, the species assumed to be responsible for the DNA intrastrand lesions.

α-Thiosubstituted chiral imines/secondary enamines: their use in the asymmetric Michael reaction

Abstract The asymmetric Michael reaction between 2-thiosubstituted chiral imines/secondary enamines derived from ( S )-1-phenylethylamine and electrophilic alkenes (methyl acrylate, MVK) was investigated. 2-Phenylthio derivatives furnished the expected Michael adducts with excellent ee. By contrast, an in situ elimination of p -toluenesulfenic acid took place when using the p -toluenesulfinyl analogs.

Development of Novel Technologies for the Synthesis of Biodegradable Pegylated Nanoparticles

Polymeric injectable carriers, able to deliver drugs or other compounds to specific sites of action for a prolonged time, represent a potential therapeutic approach for several diseases. However, therapeutic activity is compromised by particle recognition by the macrophages of the mononuclear phagocyte system (MPS) and their elimination within seconds, or minutes after intravenous injection. Blood proteins (opsonins) adsorb onto the particles surface, making them recognizable to the macrophages of the MPS.

Tetraaqua-bis(3-hydroxy-4-nitrobenzoato) Co(II) and Ni(II) complexes and diaqua-bis(2-hydroxy-4-methoxybenzoato) Zn(II) complex: crystal structure and thorough metal-coordination investigation

Reactions of Co(II) and Ni(II) salts with the monosodium salt of 3-hydroxy-4-nitrobenzoic acid (3) in aqueous solution resulted in isomorphous covalent complexes 3C and 3D, of centrosymmetric geometries. In similar conditions, 2-hydroxy-4-methoxybenzoic acid (5) led to the covalent Zn(II) complex 5A, exhibiting a marked dissymmetric geometry. The present crystallographic data with structural data for a series of closely related metal complexes previously reported allow a tentative rationalization of the solid-state architecture of such complexes. The dissymmetry in 5A was interpreted on the basis of a mixed (monodentate and bidentate) metal-ligation mode and a pyramidal coordination at the metal.