Juan Manuel López-Romero

Synthesis of Homoprotoberberines and 8-Oxoprotoberberines by Sequential Bicyclization of Phenylacetamides

Abstract The reaction of phenylacetamides with oxalyl chloride/Lewis acid provides a convergent, high-yield entry to C-homoprotoberberine and 8-oxoprotoberberine alkaloids from available starting materials. This approach was used to synthesize 8-oxopseudopalmatine starting from N-[β-(3′,4′-dimethoxyphenyl)ethyl]-3,4-dimethoxyphenylacetamide. Some C-homoprotoberberines exhibit significant cytotoxicity against human breast carcinoma cells.

A new approach to the synthesis of 4,5-dioxoaporphine alkaloids from preformed biaryl bond precursors

Abstract The synthesis of cepharadione-B and 2-demethoxy analogues is described. Starting from fluorenones, ring C was formed by cyclization of (biphenyl-2-yl)acetyl morpholines under Bischler-Napieralsky conditions. The photochemistry of chloroacetamides was used to form ring B. The cytotoxicity of these compounds on several tumor cell lines was evaluated.

Alkaloids from Fumaria sepium and Fumaria agraria

The plants of genus Fumaria L., which encompasses about 40 species (Southon and Buckingham, 1989), are annual herbs which have a wide distribution from India to Macaronesia. Twenty-two species are restricted to the Ibero-Mauritanian Region, which includes Algeria, Morocco and Spain (Liden, 1986). Plant material of Fumaria agraria Lag. (Fumariaceae) was collected from Churriana (Malaga, Spain) and that of Fumaria sepium Boiss. (Fumariaceae) from Los Barrios (Cadiz, Spain). Both were identified by the Department of Botany of the Faculty of Sciences of the University of Malaga. Voucher specimens (F. agraria MGC-23062 and, F. sepium MGC-31528) are deposited in the Faculty’s herbarium.

A versatile approach to the synthesis of 4,5-dioxoaporphine and 3,4-dioxocularine alkaloids. One-Pot sequential CB ring formation from arylacetamides

Abstract Cyclization of biarylacetamides to their phenanthrene derivatives is promoted by oxalyl chloride/stannyl chloride. The reaction proceeds with a second cyclization in which the oxalyl fragment acts as an α-dicarbonyl transfer agent to give 4,5-dioxoaporphine alkaloids in a single step. This double cyclization was also applied to aryloxyphenyl acetamides to give the corresponding 3,4-dioxocularine alkaloids. Decarbonylated aristocularine alkaloids were also formed in this case.

Raman study of the rigidity of penta-p-phenylene derivatives used as legs in molecular tripods.

Molecular planarity of penta-p-phenylene (P5P) and several substituted derivatives with four side chains of various lengths, including deca(ethylene glycol) groups, is discussed by considering the changes in the intensity ratio between the Raman bands recorded at 1280 and 1220 cm(-1). The intensity ratio between both bands I(1280)/I(1220) shows a small increase with the size of the substituent, indicating a high rigidity for all these compounds, even those with long oligo(ethylene glycol) side chains. This result is important given that these phenylene derivatives are versatile building blocks for the construction of nanometric tripod-shaped adsorbates for biological applications since the side chains should prevent the nonspecific interaction with proteins.

Synthesis of 3,4-dioxocularine and aristocularine alkaloids in a convergent route from aryloxy-phenyl acetamides involving oxalyl chloride-Lewis Acid

Double cyclization of aryloxy-phenyl acetamides is promoted by oxalyl chloride/stannyl chloride and gives 3,4-dioxocularine and aristocularine alkaloids. Rearrangement of the dibenzoxepine ring prior to the second cyclization produces xanthene derivatives. The synthesized cularinoids exhibit significant activity against various tumoral cell lines.

Pyrrolizidine alkaloids from three Spanish Senecio species

In continuation of our chemical studies on the Andalusian Flora (Valpuesta et al., 1995, 1999; Suau et al., 1998, 2002), we focused on the genus Senecio in our search for pyrrolizidine alkaloids (PAs). We collected three endemic species, viz. Senecio elodes Boiss. ex DC. (MGC 25920) and S. granatensis Boiss. (MGC 20646) from Sierra Nevada (Granada, Spain), and S. malacitanus L. (MGC 30068) from El Pantano del Agujero (Malaga, Spain). Voucher specimens are deposited at the Herbarium of the Department of Botany of the University of Malaga (MGC).

Sequential bicyclization of biphenyl acetamides promoted by (COCl)2/SnCl4. Total synthesis of 4,5-dioxoaporphines

Abstract The reaction of biphenyl acetamides with excess of oxalyl chloride/stannyl chloride offers a one pot, high-yield entry to 4,5-dioxoaporphine alkaloids. This strategy has been applied to the synthesis of 4,5-dioxodehydrocorydine starting from 1-iodo-2,3-dimethoxybenzene. The cytotoxicity of tetraoxygenated 4,5-dioxoaporphines has been evaluated.

Seeded Growth Synthesis of Gold Nanotriangles: Size Control, SAXS Analysis, and SERS Performance

We studied the controlled growth of triangular prismatic Au nanoparticles with different beveled sides for surface-enhanced Raman spectroscopy (SERS) applications. First, in a seedless synthesis using 3-butenoic acid (3BA) and benzyldimethylammonium chloride (BDAC), gold nanotriangles (AuNTs) were synthesized in a mixture with gold nanooctahedra (AuNOCs) and separated by depletion-induced flocculation. Here, the influence of temperature, pH, and reducing agent on the reaction kinetics was initially investigated by UV-vis and correlated to the size and yield of AuNT seeds. In a second step, the AuNT size was increased by seed-mediated overgrowth with Au. We show for the first time that preformed 3BA-synthesized AuNT seeds can be overgrown up to a final edge length of 175 nm and a thickness of 80 nm while maintaining their triangular shape and tip sharpness. The NT morphology, including edge length, thickness, and tip rounding, was precisely characterized in dispersion by small-angle X-ray scattering and in dry state by transmission electron microscopy and field-emission scanning electron microscopy. For sensor purposes, we studied the size-dependent SERS performance of AuNTs yielding analytical enhancement factors between 0.9 × 104 and 5.6 × 104 and nanomolar limit of detection (10-8-10-9 M) for 4-mercaptobenzoic acid and BDAC. These results confirm that the 3BA approach allows the fabrication of AuNTs in a whole range of sizes maintaining the NT morphology. This enables tailoring of localized surface plasmon resonances between 590 and 740 nm, even in the near-infrared window of a biological tissue, for use as colloidal SERS sensing agents or for optoelectronic applications.

Paclitaxel-loaded hollow-poly(4-vinylpyridine) nanoparticles enhance drug chemotherapeutic efficacy in lung and breast cancer cell lines

Paclitaxel (PTX), one of the most effective cytotoxins for the treatment of breast and lung cancer, is limited by its severe side effects and low tumor selectivity. In this work, hollow-poly(4-vinylpyridine) (hollow-p4VP) nanoparticles (NPs) have been used for the first time to generate PTX@p4VP NPs, employing a novel technique in which a gold core in the center of the NP is further oxidized to produce the hollow structure into which PTX molecules can be incorporated. The hollow-p4VP NPs exhibit good physicochemical properties and displayed excellent biocompatibility when tested on blood (no hemolysis) and cell cultures (no cytotoxicity). Interestingly, PTX@p4VP NPs significantly increased PTX cytotoxicity in human lung (A-549) and breast (MCF-7) cancer cells with a significant reduction of PTX IC50 (from 5.9 to 3.6 nM in A-549 and from 13.75 to 4.71 nM in MCF-7). In addition, PTX@p4VP caused a decrease in volume of A-549 and MCF-7 multicellular tumor spheroids (MTS), an in vitro system that mimics in vivo tumors, in comparison to free PTX. This increased antitumoral activity is accompanied by efficient cell internalization and increased apoptosis, especially in lung cancer MTS. Our results offer the first evidence that hollow-p4VP NPs can improve the antitumoral activity of PTX. This system can be used as a new nanoplatform to overcome the limitations of current breast and lung cancer treatments.