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In this review, a thorough approach was taken to the therapeutic potential of CBD and the possibilities of heterologous expression for its synthesis. Synthesizes the most recent discoveries on the medicinal benefits of CBD, its mode of action, and different methodologies that aim to maximize CBD production using heterologous expression systems. This review contributes to increasing knowledge about the wide range of uses of CBD and its potential in industries, including biotechnology and medicine.

A series of xanthone derivatives containing different side chains, including ω-bromo and ω-aminoalkoxylxanthones (with linear alkoxy chains of 3, 4 and 5 carbon atoms and methyl, propyl, tert-butylamino and piperidinyl moieties), synthesized from the natural xanthone lichexanthone were tested for their antiprotozoal activities against Leishamania braziliensis, L. major and Trypanosoma cruzi (extra and intracellular forms). The ω-aminoalkoxylxanthones showed good antileishmanial activity, with IC50 ranging from 62.8 to 0.1 µM for promastigotes and 119.3 to 2.4 µM for amastigotes. In general, compounds with longer alkyl chains and tert-butylamino moiety showed better activity. The cytotoxicity on VERO cells was also described for some derivatives. Compound 15 (tert-butylaminobutyloxy side chain) was the most active on promastigote forms (IC50 0.1 µM), compound 16 (tert-butylaminopentyloxy side chain) sowed the best activity for amastigotes (IC50 2.4 µM) and derivative 13 (dipropylaminopentyloxy side chain) was the most selective (selectivity index of 9.4). Regarding trypanocidal activity, 16 and other groups of derivatives, (ω-bromoalkoxylxanthones, prenyl and epoxyl side chains) had moderate to good activity on T. cruzi trypomastigotes, with IC50 ranging from 30.6 to 4.1 µM, while only two ω-aminoalkoxylxanthones (10 and 11) were weakly active against T. cruzi amastigotes. DOI: http://dx.doi.org/10.17807/orbital.v12i3.1460

Neste trabalho, foi planejada a síntese de lipídeos resorcinólicos análogos as citosporonas utilizando métodos clássicos de síntese orgânica. O objetivo principal foi à preparação dos compostos: ácido 2,4-dihidróxi-6-octil-benzóico (6) e 2,4-diidróxi-6-(8-oxooctil)-benzóico (7). Foram estudadas rotas de síntese visando à produção desses compostos, foi possível obtenção de três intermediários avançados, com sucesso: 2,4 dimetóxi-6-octil-benzoato de etila (8), 2-hidróxi-4-metóxi-6-octil-benzoato de etila (9) e ácido 2-hidróxi-4-metóxi-6-octil-benzóico (10), os quais tiveram suas estruturas determinadas por técnicas de espectroscopia de RMN de 1H e de 13C, e no caso de (10) incluindo técnicas bidimensionais (HSQC e HMBC).

The standard style of Orbital should be followed. Prospective authors should consult any current issue of Orbital for examples of this style. The manuscript shall be prepared in accordance with the template available at: Template (New 2021)

Resorcinolic lipids, a class of bioactive amphiphilic molecules found widely in nature, hold potential for a variety of biological and industrial applications. This report describes the synthesis of three bioactive structural analogues of resorcinolic lipids, obtained by subjecting ethyl (E)-2-undecenoate and ethyl acetoacetate to a Michael reaction in the presence of sodium ethoxide to generate a Michael adduct, followed by cyclization in the reaction medium. Ethyl 2-octyl-4,6-dioxocyclohexanecarboxylate (7) was thus produced with a 60% yield. To perform an aromatization step, 7 was subsequently treated with I2 in methanol under reflux, producing a combined 80% yield of 2,4-dimethoxy-6-octyl-ethyl benzoate (1) and 2-hydroxy-4-methoxy-6-octyl-ethyl benzoate (2) at a 7:3 ratio, respectively. 2-Hydroxy-4-methoxy-6-octyl-benzoic acid was obtained with a 60% yield by treating 1 with BBr3/CHCl3. The structures of the synthesized compounds and intermediates were elucidated by 1H and 13C NMR spectroscopy, employing two-dimensional techniques (HSQC and HMBC). DOI: http://dx.doi.org/10.17807/orbital.v12i2.237

Heavy consumption of non-renewable raw materials and/or renewable energy production produces environmental imbalance. Thus, the search for a means of sustainable and environmentally appropriate life requires scientific research in new renewable biofuels. The Calotropis procera, exotic oilseed widely distributed is a hardy shrub well suited to the northeast that produces seeds with oil. So, in this work were made fruit collection, drying, extraction and analysis of physical, chemical and thermal properties of oil aiming its use in biodiesel synthesis. The oil was extracted with Soxhlet method and characterized through physical-chemical, thermal analysis, and FTIR and NMR spectroscopy analysis. The results indicate that it is possible to obtain 21% ± 2 by weight of an oil physicochemical quality within the standard recommended by the legislation, except for the acid value was high and indicates that the best way to transesterification it is to make the catalyzed by acid or heterogeneous. The thermal analysis showed that the oil has high purity and is constituted by two material strips of different mass or molecular structures and has high thermal stability and convenient for the synthesis reaction. FTIR and NMR spectroscopy confirmed that the major compounds present in the oil are saturated and unsaturated fatty acids. DOI: http://dx.doi.org/10.17807/orbital.v10i2.1061

Two novel hybrid lichexantone-THC (benzopirane group) derivatives as potential antimicrobial agents were designed and prepared from norlichexanthone and (S)-cis-verbenol in two steps. The newly synthesized compounds were characterized by 1H-NMR, 13C-NMR and MS. In addition, we evaluated the in vitro antimicrobial activity against Gram-positive (Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium) and Gram- negative (Escherichia coli, Enterobacter cloacea, Klebisiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa) bacterial strains. The bioassay results indicate that the compounds namely 5 and 6 proved active against Gram-positive strains (standard and clinical) in comparison with reference drugs. DOI: http://dx.doi.org/10.17807/orbital.v7i4.788

Octocrylene (2-ethylhexyl 2-cyano-3,3-diphenyl-2-propenoate) is present in several sunscreens and is known to work synergistically with UV filters. We prepared eight octocrylene-related compounds to test their photoprotective activities by measuring diffuse transmittance. The compounds had varied photoprotection profiles, with Sun Protection Factors (SPF) ranging from 1 to 5 and UVA Protection Factors (UVAPF) ranging from 1 to 8. Compounds 4, 5, and 7 showed the best protection against UVB sunrays, while compounds 5, 6, and 7 presented the best results for protection from UVA, so compound 7 had the most balanced protection overall. Results for compounds 4, 8, and 9 are reported for the first time in the literature.

Derived from ozonetherapy, the ozonized oils represent an Ozonized oils represent an interesting pharmaceutical approach to the management of a variety of dermatological pathologies. Ozone reacts with carbon-carbon double bonds of unsaturated fatty acids according to the mechanism described by Criegee, forming ozonides or 1,2,4 trioxolane rings and peroxides as the most important products, responsible for the antimicrobial activity and stimulating tissue repair and regeneration properties. The ozonized vegetable oils can be liquids or semisolids at room temperature and have stability periods that may be adequate for commercial distribuition. Ozonized sunflower oil (Oleozon®), a drug registered nationally and developed in the Ozone Research Center in Cuba has been tested and it was found to have valuable antimicrobial activity against bacteria, fungi and virus. FT-IR and NMR technics are used to confirm the structural changes undergone by oil during the ozonation. For determining the quality of ozonized oils, analytical methods such as peroxide, acidity and iodine values are usually carried out. Products are available for an alternative use of available resources, natural and renewable sources, simple technology, low cost and with extensive biological activity with reduced collateral effects. DOI: http://dx.doi.org/10.17807/orbital.v4i4.467

We extended our previous exploration of sulfur bridges as bioisosteric replacements for atoms forming the bridge between the aromatic rings of combretastatin A-4. Employing coupling reactions between 5-iodo-1,2,3-trimethoxybenzene and substituted thiols, followed by oxidation to sulfones with m-CPBA, different locations for attaching the sulfur atom to ring A through the synthesis of nine compounds were examined. Antitubulin activity was performed with electrophoretically homogenous bovine brain tubulin, and activity occurred with the 1,2,3-trimethoxy-4-[(4-methoxyphenyl)thio]benzene (12), while the other compounds were inactive. The compounds were also tested for leishmanicidal activity using promastigote forms of Leishmania braziliensis (MHOM/BR175/M2904), and the greatest activity was observed with 1,2,3-trimethoxy-4-(phenylthio)benzene (10) and 1,2,3-trimethoxy-4-[(4-methoxyphenyl) sulfinyl]benzene (15).

In an attempt to obtain Michael adducts in aqueous medium, 1,3-cyclohexanedione (1) or dimedone (2) and acetylenedicarboxylic acid monopotassium (3) were dissolved in water and heated to reflux. Under these conditions, two products were isolated from the reaction mixture between 1 and 3: 2-[1-(2,6-dioxocyclohexyl)ethyl]-1,3-cyclohexanedione (6) and a xanthenedione (7), which corresponds to the cyclization of 6. The reaction between 2 and 3 gave only the 2-[1-(4,4-dimethyl-2,6-dioxocyclohexyl)ethyl]-5,5-dimethyl-1,3-cyclohexanedione (8).

A series of 15 ω-aminoalkoxylxanthones containing methyl, ethyl, propyl, tert-butylamino and piperidinyl moieties were synthesized from a natural xanthone isolated from a lichen species. These compounds were tested for their in vitro antibacterial properties against Gram-positive and Gram-negative bacteria and cytotoxicity against a number of human tumor cell lines was too evaluated. The newly synthesized derivatives revealed selective activity against Staphylococcus aureus (Gram-positive), and the most promising results are for a multidrug resistant strain, for which six of these compounds showed good activity (MICs 4 µg/mL). Many derivatives inhibited tumor cells growth and most compounds were active on multiple lines.

Presently glycerol is considered a co-product of biodiesel industry. As the biodiesel production is exponentially increasing, glycerol generated from the transesterification of vegetable oils and fats is also being produced on a large scale, and turned out to be essential seeking for novel alternatives to the consumption of the extra volume, in crude and/or as derivatives high added value. This review mainly deals with chemical and enzymatic transformations of glycerol to obtain chiral building blocks for synthesis of pharmaceuticals and natural products.

We study theoretically the amodiaquine-adenine and amodiaquine-guanine adducts formation using Density Functional Theory (B3LYP) and the 6-31G(d) basis set for the geometry optimizations and 6-31+G(d,p) for the analysis of the global indexes: electrophilicity (w), electronic chemical potential (m), hardness (h) and softness (S), based in the Frontier Molecular Orbital Theory – FMO. Local softness for nucleophilic reaction (sk+) sites over guanine was evaluated using Fukui function (f k). We also evaluated the guanine Electrostatic Potential (EP) values using the (MSK) charge scheme. The theoretical calculations had demonstrated that the amodiaquine has greater electronic affinity for the guanine, with irreversible formation of the amodiaquine-guanine adduct, as reported before on a previous experimental work.

The electrochemical behavior of the interaction of amodiaquine with DNA on a carbon paste electrode was studied using voltametric techniques. In an acid medium, an electroactive adduct is formed when amodiaquine interacts with DNA. The anodic peak is dependent on pH, scan rate and the concentration of the pharmaceutical. Adduct formation is irreversible in nature, and preferentially occurs by interaction of the amodiaquine with the guanine group. Theoretical calculations for optimization of geometry, and DFT analyses and on the electrostatic potential map (EPM), were used in the investigation of adduct formation between amodiaquine and DNA.

This work presents a preliminary screening directed to obtaining optically active glycerol derivatives. It was tested six lipases from different sources as a means for kinetic resolution.

Inspired by the structure and biological activities of resorcinolic lipids and, particularly cytosporone A- a potent inhibitor of plantule germination and growth, we have performed the synthesis of the analogs 3-heptyl-3-hydroxy-5,7-dimethoxy-2-benzofuran-1(3H)-one (1) and 3-heptyl-3-hydroxy-4,6-dimethoxy-2-benzofuran-1(3H)-one (2). The intermediates and products were submitted to allelopathic test using Lactuca sativa L. seeds. Target compound 1 showed an inhibitory effect on germination and growth of hypocotyl and radicle in milimolar range.

From the lichen Parmotrema lichexantonicum were isolated the depsidone salazinic acid, the xanthone lichexanthone, and the depside atranorin. The two major compounds, salazinic acid and lichexanthone, were selected for structure modifications. Salazinic acid afforded O-alkyl salazinic acids, some of them potentially cytotoxic against tumor cell lines (HCT-8, SF-295 and MDA/ MB - 435). From lichexanthone were obtained norlichexanthone, 3-O-methylnorlichexanthone, 3-O-methyl-6-O-prenylnorlichexanthone, 3,6-di-O-prenyl-norlichexanthone, 3,6-bis[(3,3-dimethyloxyran-2-il)methoxy]-1-hydroxy-8-methyl-9H-xanten-9-one and 3,6-bis[3-(dimethylamine)propoxy]-1-hydroxy-8-methyl-9H-xanten-9-one. The last compound was the most active against S. aureus.

The sesquiterpene (+)-allo-aromadendrane-10b-14-diol 1 was the lead compound to the preparation of several derivatives in order to test their biological activity against A. salina, C. sphaerospermum, E. coli and S. aureus. In this way the monoalcohols (+)-viridiflorol 4, 9 and 11 were synthesized from 1 together with the acetal 6, the ketal 7, and the ketone 8. The oxirane 3 and nitrile 5 were also prepared using as an intermediate the tosylate derivative 2.

Orbital - The Electronic Journal of Chemistry is entering its 4th year of existence which is a reason to celebrate. A great work has been devoted to preserve a scientific journal of international reputation. This work was not always without mistakes or any trouble. However, these very adversities stimulate additional efforts in order to overcome our errors and, continuing with our serious proposal of editing a journal which scientists from all over the world can submit online their original works manuscripts to be published in peer review and open-access style. Beginning this year, Orbital was classified by the Chemistry Coordination Area on the B5 rank of CAPES Qualis (Brazil) and, leveled as B4 by Coordination Areas of Materials and Engineering II. These important details demonstrate that Orbital is progressively attaining the acknowledgment of the Brazilian scientific community. The recognition by CAPES Qualis is crucial as the system evaluates the generation of knowledge in the Brazilian universities and the method by which this same knowledge disseminated to society. Not all these were possible without endeavoring of editors and volunteer assistance of advisors from several national and international institutions. Recently, the young Professors Kleber Thiago de Oliveira (UFSCAR), Grégoire Demetz (USP-RP) and Amilcar Machulek Júnior (UFMS) have joined us to share the idea and philosophy of Orbital by accepting our invitation to be associated editors. The tasks and challenges are enormous and, we are sure that new participants will support us on the way to achieve indexation in new Databases systems as SCOPUS, ISI and Scielo. Consequently, the international success of this electronic journal will be assured. We sincerely hope that in the academic Brazilian scenario, Orbital can figure as a solid bridge to interchange real creative science that is happening in various locations around the world.

Over the past century, chemical and pharmaceutical industries have made substantial strides in the development of new pharmaceuticals for a range of human diseases. Discovering and developing new drugs are part of a costly process that involves not only the search for new drug candidates, but also the performance of clinical trials. It is not uncommon to find reports of costs reaching US$ 500 million—and even US$ 1 billion—engaging multidisciplinary teams for periods of 10 or 15 years. To a large extent, these costs are borne by consumers in richer countries. In contrast, diseases that predominantly affect residents of poorer nations tend to be left out of the modern process of drug discovery. Moreover, most of the world population stricken by these illnesses is incapable of supporting the costs involved in developing the drugs they need. Because these infirmities, with few exceptions, have been ignored by those in charge of research programs, both in the public and private sectors, they have been referred to as neglected diseases. On its website, the World Health Organization categorizes 14 health conditions as “tropical diseases,”.......................

In 2004 the Brazilian Program for Biodiesel Production and Use (PNPB) was launched by the Federal Government, aimed at the production of alternative, non-fossil fuels and, more broadly, at the country’s economic development [1]. On January 13, 2005, Law 11097 was passed, establishing the inclusion of biodiesel in Brazil’s energy balance and mandating the addition of 2% biodiesel (B2) to the composition of diesel by 2008, a ratio to be increased to 5% by 2013 (B5) [1, 2]. Because all diesel oil sold in Brazil has contained as much as 3% of biodiesel (B3) since 2008, a glycerol surplus of the order of 100 000 tons a year is now projected for the Brazilian market—a huge increase from the traditional domestic production of around 30 000 tons a year. In 2013, when the B5 standard goes into effect, the yearly output of glycerol is forecast at 250 000 tons [3]. In the European Union, fuels for vehicles will be required to contain at least 5.75% of biocomponents obtained from renewable sources by the end of 2010. If this target is achieved, it should increase the European demand for biodiesel to over 10 million tons a year by 2010, leading to an annual generation of nearly 1 million tons of glycerol as a co-product...........

Vegetable oils are rich in mono-and poly-unsaturated fatty acids, and these compounds contain carbon-carbon double bonds available for chemical/structural modification, especially via oxidative processes. Sunflower oil obtained from seed of sunflower (Helianthus annuus) contains a large amount of these acids, such as linoleic (48-74%) and oleic (14-39%) acids, proving to be an ideal starting material for these changes [1]. Ozone is an oxidizing agent that reacts with double bonds of fatty acids present in vegetable oils to form ozonides or 1,2,4 trioxolanes, and peroxidic species such as hydroperoxides, hydrogen peroxide, polymeric peroxides and other organic peroxides. These compounds are of great pharmaceutical interest for the treatment of various dermatological diseases, due to their antimicrobial properties and stimulating action on tissue repair and regeneration [2]. In this work, the sunflower oil was ozonized, and the ideal conditions, as reaction time, ozone concentration and temperature, were determined. The IR and 1H and 13C NMR of ozonized oils confirm the formation of 1,2,4 trioxolane ring according to the mechanism proposed by Criegee [3]. The ozonolysis reaction was performed under different conditions and the product is in the process of knowledge protection or patent.

Stereochemistry control is very important in organic synthesis and it is a basic challenge in asymmetric synthesis. An approach widely used is making use of chiral auxiliary compounds. In this work it is showed the synthesis of highly optically pure rigid polycyclic compounds from the Diels-Alder adduct 1. Compounds 1-3 were prepared as described by Ito et. al. [1]. The alcohol (-)-3 was obtained by biotransformation of diketone 2 with Mucor ramosissimus, e.e.>99% (60%). The polycyclic halides 4-6 were synthesized (60-97%) after treatment of alcohol (-)-3 with NBS, NIS and, NCS in dichloromethane, respectively. Compound 7 was prepared by reaction with p-toluenesulfonic acid, whilst 8 was prepared by treatment of (-)-3 with m-chloroperbenzoic acid. The strained polycylic alcohols 9-13 will be achieved by reduction of ketones 4-8 with NaBH4. All compounds were identified by 1H and 13C NMR spectroscopy. Due to intrinsic rigidity of the synthesized polycyclic, they could be of use as chiral auxiliary agents. Prochiral substrates can be readily attached by many ways to C-3 or through hydroxyl group found in compounds 8-13. The stereo-dirigent potential of these polycyclic can also be increased by directly or indirectly introduction of many groups at position C-3, or at adjacent positions to carbonyl or hydroxyl at C-3 and C-10.

The use of microorganisms or isolated enzymes in synthetic routes has been extensively used by industry and academic research. A great advantage of biotransformation in a synthetic route is highly regio- and enatiosselective control, which can be achieved through microbial catalyzed reaction. Biotransformation is one of the most efficient methods in a production of high purity optical compounds and development of efficient routes for target molecules. Biotransformation by Mucor ramosissimus of enedione 1 gave the keto-alcohol (-)-2 with enantiomeric excess (ee)>99,9% (determined by 1H NMR with [(+)-Eu(hfc)]3) and their epimer (-)-3. Determination of the absolute configuration of epimer (-)-3 was accomplished by controlled reaction and measuring of optical rotation (scheme 1). The fungus M. ramosissimus is a promising species to perform desymmetrization of diketones with high enantioselectivity.

Recently, studies aiming to preparation of nanomaterials for application in high technology areas are very advanced in developed countries. Liquid crystals have a vast application and for that; many researches are focused on the development of these special molecules. Polyarylacetylenes are polymers that can hold helicity if polymerization of the monomer occurs in the presence of appropriate metal catalysts. The aiming of this work is to prepare side-chain crystal-liquid helicoidal chiral polymers. These systems show a molecular structure in which the mesogenic unity (pendant) is sided-attached to the polymeric chain. If a chiral substituent is incorporated to the monomer, it will induct chirality of the polymer. Glycerol [1] and cardanol [2], obtained from renewable source, were formally coupled to form the epoxide 1 that in turn was treated with 4-ethylanyline in CHCl3 at 120 oC in a sealed tube in the presence of pyridine, furnishing monomer 2 (40%). The next step it will be the enzymatic resolution of the alcohol 2 in order to achieve optical pure 2. Sequentially, from monomer 2, it is going to be synthesized the targeted stereoregular cis-trans polymer following known procedures, using [Rh(nbd)Cl]2 (nbd=2,5-norbornadiene) as the catalyst [4].

Porphyrins are very attractive compounds due to their wide application in many areas of new materials as chemical technology, ecology, medicine and, electronics. In the last years, they are also been a focus of attention owing to their implications to many photocatalytic reactions. Cardanol (isolated form cashew nut shell liquid) and glycerol (side product of biodiesel industry) are raw materials of low aggregated value; however, they hold chemical structures with functionalities that can lead to products of high commercial value to Brazilian industry. Aiming to use these chemical materials, our research group has proposed the synthesis of new hybrid molecular structures of porphyrin-cardanol-glycerol, which will be submitted to test of their photocatalytic properties. The synthetic proposal is based on the reaction of 4-hydroxybenzaldehyde (1) and epichloriridine (2) (derived from glycerol), using pyridine in dichloromethane and FeCl3 as a catalyst, under reflux and stirring. This process will provide the mixture of intermediate 3 and 4. These compounds will be attacked by the nucleophile cardanol (5) in sealed tube, using pyridine and dichloromethane at 120 ºC for 80 hours, giving the intermediate 6. After oxidation of the alcohol 6, the corresponding ketone will be achieved. Continuing the synthesis, these intermediates will separately react with pyrrol, giving the wished porphyrins that in turn will be transformed in macromolecules by treatment with Grubbs catalyst, according to methodologies already known in the literature. The previously synthesized compounds 3, 4, 5 and 6 had their structures confirmed by spectroscopy analyses of NMR (1H and 13C).

This work presents two proposals for the synthesis of halogenated aryl thiosulfonates which are of biologically interesting compounds. Inhibitors of proteases and juvenile hormone mimetizing are already successfully employed for managing pest-insects However, many of these products can be always improved in the aspects of specificity implying in low cost to the farmer. The major objective of this work is the synthesis of thiosulfonates analogues of commercial products which are inhibitors of serine-protease and juvenile hormone mimetizing compounds that can be applied as leads for production of insecticides that can contribute to the control of pest-insects in economically important plantation and stored grains. The scientific research group SINTMOLB (CNPq) is involved with studies related to the synthesis of phenolic compounds with insecticidal potential. Some important results have already been obtained and, in this new project, it is being explored the synthesis of new compounds, computational analysis, and biological tests to evaluate protease inhibitory effect.