Current Organic Synthesis - Volume 11, Issue 1, 2014

Porphyrin macrocycles have been the subject of intense study in the last century because they are widely distributed in nature, usually as metal complexes of either iron or magnesium. As such, they serve as the prosthetic groups in a wide variety of primary metabolites, such as hemoglobins, myoglobins, cytochromes, catalases, peroxidases, chlorophylls, and bacteriochlorophylls; these compounds have multiple applications in materials science, biology and medicine. This article describes current methodology for preparation of simple, symmetrical model porphyrins, as well as more complex protocols for preparation of unsymmetrically substituted porphyrin macrocycles similar to those found in nature. The basic chemical reactivity of porphyrins and metalloporphyrin is also described, including electrophilic and nucleophilic reactions, oxidations, reductions, and metal-mediated cross-coupling reactions. Using the synthetic approaches and reactivity profiles presented, eventually almost any substituted porphyrin system can be prepared for applications in a variety of areas, including in catalysis, electron transport, model biological systems and therapeutics.

The development of efficient synthetic methodologies and post-functionalization procedures gave access to a wide variety of new corrole derivatives with potential applications in different areas. This paper reviews the preparation of meso-triaarylcorroles and their functionalization, namely via cycloaddition transformations, and describes the nonlinear optical (NLO) properties of a series of metal-free and gallium corroles with different peripheral substituents. The corroles studied were the free base 5,10,15-tris- (pentafluorophenyl)corrole, the corresponding gallium(III) complex and adducts obtained from 1,3-dipolar cycloaddition reaction. Correlations between the structure and the NLO effect of optical power limiting were attempted in our comparative analysis. The present contribution is one of the first reports on the effect of reverse saturable absorption in the visible spectrum generated by corrole-based complexes.

Chlorin derivatives have attracted considerable attention over the last three decades in different scientific fields. These compounds are present in a large number of bacteria, fungi and in all plants found on Earth. Since the discovery of these pigments, chemists, biologists, medical professionals and materials scientists have devoted pronounced efforts in order to develop new synthetic methods and discover useful applications for these compounds. In this review we wish to cover the main natural chlorins, their natural sources, synthetic approaches to access these compounds, and the major applications.

Methods for the synthesis of mono-, di-, and tetra-glycosylated phthalonitriles are described, which are key building blocks for the preparation of the corresponding glycosylated metal (mostly zinc) phthalocyanines. Than the preparation of symmetrically and unsymmetrically tetra- and octa-glycosylated zinc phthalocyanines in which the carbohydrate is attached either anomerically or via another one of its OH-groups to the phthalocyanine macrocycle is assessed.

Metalloporphyrins effectively catalyze C-H bond functionalization, including C-O (hydroxylation), C-N (amination), and C-C bond formation (carbene insertion). Over the last 20 years, numerous papers have reported that these complexes display catalytic efficiency and selectivity (regioselectivity and enantioselectivity) in solution (homogeneous catalysis). Green chemistry advocates idealization and production of more efficient, selective, and preferably recyclable catalysts to develop technological processes that are increasingly aligned with the principles. This has encouraged investigations into processes that can heterogenize efficient metalloporphyrin (MP) catalysts. Indeed, scientists have more and more often used heterogeneous catalysis as a tool to design clean and green processes. In this context, silica and its many functionalized derivatives represent an excellent strategy to obtain inexpensive, inert, and often highly pure (depending on the preparation route) supports to immobilize catalytic species. In this review, we intend to address this issue.

This paper describes past and current microwave-assisted methodologies for the synthesis of porphryins and porphyrin derivatives, including porphyrin precursors such as dipyrromethanes. The review is organized in two main topics, porphyrin synthesis and porphyrin reactivity under microwave irradiation and covers solventless and solution reactions.

In medical applications such as drug delivery, gene transfection and imaging the formation of systems with well-defined sizes and shapes are of significant interest. For this reason the design of dendrimers with modulated size, shape, branching length/density, and their surface functionality, clearly distinguishes these structures as unique and optimum carriers for medical applications. The bioactive agents may be encapsulated into the interior of the dendrimers or chemically attached/physically adsorbed onto the dendrimer surface, with the option of tailoring the carrier to the specific needs of the active material and its therapeutic applications. In this regard one area with growing attention is photodynamic therapy (PDT) where a photosensitizer combined with light and molecular oxygen can easily cause irreversible damage to the target tissue. Nevertheless most of the photosensitizers have solubility issues when attempts are made to dissolve them in aqueous environments, hampering in most cases their medical applicability. Currently, investigations are running towards the combination of these photosensitizers with dendrimers increasing their organization, solubility and specificity to the target tissues. In this communication we review the latest advancements in the synthesis of porphyrin and phthalocyanine dendrimer architectures, regarding their utility as biomedical agents.

The field of imaging science is growing immensely, with the emergence of “noninvasive” in vivo imaging technologies and imaging probes like Positron Emission Tomography (PET), Fluorescence Imaging (FI) and Magnetic Resonance Imaging (MRI), to observe events at molecular and cellular levels, and consequently to speed up drug development processes. For instance, the imaging of cancer specific molecular targets ought to permit precocious diagnosis and superior evaluation to oncology patients. Porphyrins and their derivatives (or related compounds, like phthalocyanines) represent one of the oldest, most widely studied chemical structures, both in nature and in biomedical applications. They display intrinsic affinity for tumor localization and their well-portrayed photophysical and photosensitizing properties can lead to their potential use as sensitizer in a variety of in vivo imaging technologies. This contribution will review recent developments involving tetrapyrrolic -based sensitizers for cancer detection, with emphasis on PET, FI and MRI technologies.

The electrochemical synthesis of o-benzoquinones and their in situ transformation is a versatile approach for the synthesis of polyhydroxylated aromatics. In the present paper, the electrochemical oxidation of catechol in the presence of ketene N,S-acetals as N,Cdoubly nucleophiles was first investigated using cyclic voltammetry technique. Then preparative scale of electrolysis was carried out to demonstrate that polyfunctionalized indoles could be one-pot synthesized under constant current electrolysis conditions. Finally, the reaction mechanism was proposed.

In this paper, we present for the first time the synthesis in satisfactory yields and characterization of a new family of five Npolyetheralkyl- 3,5-pyrazole derived ligands (L1-L5) as well as regioselectivity studies by NMR techniques. Ligands L1, L2, L3/3’, and L4/4’ were obtained by N-alkylation reaction, whereas for L5 O-alkylation reaction was followed. In N-alkylation, the alkylating agent was 1-chloro-2-[2-(2-methoxyethoxy)ethoxy]ethane, NaOEt as base and dry toluene as solvent. In O-alkylation, the alkylating agent is 1- chloro-2-[2-(2-methoxyethoxy)ethoxy]ethane, metallic Na as a base and dry tetrahydrofurane as solvent. In general, the two methods lead to high yields (60-95%), with reaction times of 24 h, except for L2 (48 h). All synthesized ligands have been characterized by elemental analyses, electrospray mass spectra, infrared spectra, 1H, 13C{1H} and HSQC NMR spectroscopy. Furthermore, the different regioselectivity observed in the synthetic reactions of pyrazole precursors with one pyridyl substituent has been rationalized from theoretical calculations. All together proves that the different behavior depends on whether the rate determining step is the SN2 reaction or the formation of the precursor complexes between pyrazolide-Na+ chelates and the polyether chloride chain. The application of this new family in supramolecular crystal engineering is interesting due to the different bonding properties of the heteroatoms (N vs. O) present in the structure of the ligands.

Tert-butylnitrite was proved to be an efficient oxidant for the selective oxidation of sulfides to sulfoxides. The reaction was promoted by Fe(NO3)3·9H2O under mild conditions and various substrates were effectively converted into the corresponding sulfoxides in good yields and excellent selectivity.

The addition of dialkyl phosphites or diphenylphosphine oxide to the triple bond of dialkyl acetylenedicarboxylate may result in mono- and/or bisadducts. The ratio of the products may be influenced by the molar ratio of the reactants and the conditions (temperature of microwave irradiation and reaction time). Stereospecific 3JPP couplings were utilized in the assignments to the meso and racemic forms of the bisadducts. The bis(dialkylphosphonyl)-succinates were formed as a mixture of the corresponding meso form and racemate, while bis(diphenylphosphinoyl)-succinate was obtained as a racemate. The 31P–12CH–13CH–31P spin system of bis(dialkylphosphonyl)-succinates was subjected to a detailed NMR analysis supported by simulation.