Diastereoselective Synthesis of (-)-6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic Acid via Morpholinone Derivatives.

A simple and convenient synthesis of (-)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid is described, applying a combination of two synthetic methods: the Petasis reaction and Pomeranz-Fritsch-Bobbitt cyclization. The diastereomeric morpholinone derivative N-(2,2-diethoxyethyl)-3-(3,4-dimethoxyphenyl)-5-phenyl-1,4-oxazin-2-one formed in the Petasis reaction was further transformed into 1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid via Pomeranz-Fritsch-Bobbitt cyclization, a classical method of synthesis leading to the tetrahydroisoquinoline core. We review important examples of applications of the Pomeranz-Fritsch process and its modifications in the synthesis of chiral tetrahydroisoquinoline derivatives that have been published in the past two decades.

Warning system for potential releases of chemical warfare agents from dumped munition in the Baltic Sea.

The research aimed to determine the scale of the potential contamination of the southern Baltic by substances from dumped chemical weapons, in the context of applying a strategy for detecting the potential releases of toxic materials. The research included the analysis of total arsenic in sediments, macrophytobenthos, fish, and yperite with derivatives and arsenoorganic compounds in sediments and as an integral part of the warning system the threshold values for arsenic in these matrices were set. Arsenic concentrations in sediments ranged from 11 to 18 mg kg-1 with an increase to 30 mg kg-1 in layers dated to 1940-1960, what was accompanied by the detection of triphenylarsine (600 mg kg-1). The presence of yperite or arsenoorganic-related chemical warfare agents was not confirmed in other areas. Arsenic ranged from 0.14 to 1.46 mg kg-1 in fish and from 0.8 to 3 mg kg-1 in macrophytobenthos.

Mercury in the Polish part of the Baltic Sea: A response to decreased atmospheric deposition and changing environment.

Our review of the literature showed that since the beginning of the socio-economic transformation in Poland in the 1990s, the downward trend in Hg emissions and its deposition in the southern Baltic Sea was followed by a simultaneous decrease in Hg levels in water and marine plants and animals. Hg concentrations in the biota lowered to values that pose no or low risk to wildlife and seafood consumers. However, in the first decade of the current century, a divergence between these two trends became apparent and Hg concentrations in fish, herring and cod, began to rise. Therefore, increasing emission-independent anthropogenic pressures, which affect Hg uptake and trophodynamics, remobilization of land-based and marine legacy Hg deposits, as well as the structure of the food web, can undermine the chances of reducing both the Hg pool in the marine environment and human Hg exposure from fish.

Synthesis of new substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids containing a tetracyclic tetrahydroisoquinoline core structure.

A convenient and simple protocol has been developed for the synthesis of a series of new tetracyclic tetrahydroisoquinoline derivatives, 7,12-dihydro-6,12-methanodibenzo[c,f]-azocine-5-carboxylic acids by three component Petasis reaction with the use of aminoacetaldehyde acetals bearing substituted benzyl groups as the amine components followed by Pomeranz-Fritsch double cyclization reaction. By applying this method, several acids have been prepared in satisfactory yields. An unprecedented chemical behavior of a Petasis reaction product in diluted HCl solution leading to the formation of a phenylglycine derivative has been observed and the mechanism explaining such reactivity has been proposed.

Alimentary exposure and elimination routes of rare earth elements (REE) in marine mammals from the Baltic Sea and Antarctic coast.

Marine mammals found at the top of the trophic pyramid are excellent bioindicators of pollutants in the marine environment, the concentrations of which increase along with the trophic level of the organism. As these animals are usually protected species, their contamination has to be assessed non-invasively by analysing excrement and epidermal structures such as fur or claws. The present study involved testing the excrement and fur of the grey seal (Halichoerus grypus) from the Southern Baltic coast and the Southern elephant seal (Mirounga leonine) from Admiralty Bay, along with fish muscle (food) and the lithological background of both areas, for the presence of rare earth elements (REE). The soil on the Baltic coast is characterized by the predomination of light rare earth elements (LREE): yttrium, lanthanum and cerium (∑REE = 7.86 mg·kg-1 dw). In the soil and bedrock of Admiralty Bay all REEs were found except for terbium, thulium and lutetium (∑REE = 96.1 mg·kg-1 dw). The REE levels found in the muscles of Baltic herring (∑REE = 0.057 mg·kg-1 ww) were lower than those in the muscles of marbled rockcod (∑REE = 0.540 mg·kg-1 ww). The situation was analogous in the mammals, with the REE concentrations in grey seal fur (∑REE = 0.489 mg·kg-1 dw) and excrement (∑REE = 0.676 mg·kg-1 dw) being lower than those found in the fur (∑REE = 10.1 mg·kg-1 dw) and excrement (∑REE = 83.6 mg·kg-1 dw) of the elephant seal. The LREE/HREE partition coefficients in the grey seal excrement (3.37) and its fur (4.00), but also in the faeces of the elephant seal (2.63) and its fur (2.65), indicate that in each species the process of elimination from the body occurs in similar proportions.

Fur and faeces - Routes of mercury elimination in the Baltic grey seal (Halichoerus grypus grypus).

This study focused on evaluating the elimination of Hg by Baltic grey seals (Halichoerus grypus grypus) via faeces and pelage. In addition, we investigated the potential for ecosystem contamination via these routes. Faeces and fur were collected in 2014-2017 from captive adult grey seals and their pups. The concentrations of total mercury (THg) and methylmercury (MeHg) were measured in the samples. The amount of mercury eliminated in a labile form (the sum of the bioavailable Hg(II) and methylmercury) was also determined. An adult seal removed about 46% of mercury supplied with food via the faeces, of which only 17% was MeHg. Considering that mercury is mainly supplied to the body as MeHg, it can be assumed that mercury excreted along with faeces has undergone transformation inside the animal body. Despite the much higher THg and MeHg concentrations measured in fur, the incorporation of mercury into newly formed fur is a less effective method of Hg elimination removing just 4% of mercury entering the body via the alimentary route. The presence of mercury in lanugo is evidence of maternal transfer. First droppings of the pups were characterised by the highest content of MeHg and a low THg concentration. Then, despite the limited supply of mercury with food, and the rapid growth of the pup, the concentration of THg increased, suggesting that mercury started to be transformed into less toxic forms. It was estimated that faeces and fur expelled by seals could deliver about 800 g of mercury to the Baltic Sea. For both faeces and fur, most of the mercury (>95% for excrements and >85% for fur) was expelled in a labile form that can be quickly recycled.

Halogenated organic compounds in the eggs of aquatic birds from the Gulf of Gdansk and Wloclawek Dam (Poland).

Diet is the major route of exposure to environmental contaminants in biota and, after penetration into an organism, xenobiotics continue to accumulate in the body. In birds the egg-laying process acts as a transfer mechanism for the accumulated pollutants and results in the burdening of the next generation at an early stage of development. This transfer has a strong influence on developmental disorders and even breeding success. With this in mind polybrominated diphenyl ethers (PBDE), polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo furans (PCDD/Fs), as well as polychlorinated biphenyls (PCBs), were analyzed in the eggs of aquatic birds from different habitats and with different diet preferences. The highest concentration of PBDE was noted in gull eggs (198.31 ng g-1 dw.) and the lowest in tern eggs (sandwich tern: 76.96 ng g-1 dw.; common tern: 113.73 ng g-1 dw). Deca-BDE was detected only in herring gull eggs from the Wloclawek reservoir. PCDDF/s were found in the eggs of terns from the southern coast of the Baltic Sea and gulls from an inland reservoir (dam) on the River Vistula close to the town of Wloclawek. The highest toxicity (birds Toxic Equivalent Factor) was found in the eggs of terns (sandwich tern - 93.97 pg g-1 dw., common tern - 68.35 pg g-1 dw.), and this was found to be several times higher than in herring gull eggs (18.80 pg g-1 dw.). Non-dioxin like PCBs were ten times higher than other analyzed PCB congeners, but the congener pattern was similar to other studies.

Changes in total mercury, methylmercury, and selenium blood levels during different life history stages of the Baltic grey seal (Halichoerus grypus grypus).

Using the blood of grey seal pups, the blood and milk of female grey seals inhabiting the Hel Marine Station of Gdansk University's Institute of Oceanography (HMS), we monitored the transfer of total mercury (THg), methylmercury (MeHg), and selenium (Se) with blood during foetal life and nursing. Changes in the concentration of mercury and selenium were characterised in the pups' blood during their first three months of life when they transition from suckling, to a post-weaning fast, to eating fish. In the blood of pregnant females, there was a significant decrease in THg and MeHg concentrations throughout the gestation, indicating the transfer of these toxins through the placenta into the foetus. At no other stage of the pup's development was there such a high level of THg and MeHg as on the day of birth, despite the incorporation of mercury into the lanugo during foetal growth. This suggests that the maternal transfer of mercury during gestation may be the time of greatest mercury exposure for a young seal pup. The consumption of milk caused a rapid increase in weight and a lowering of the mercury level in the blood in the subsequent days of the pups' life. The postweaning fast was the period of the lowest mercury concentration. The switch to a diet consisting of fish caused a systematic increase in the concentration of mercury in the blood of the pups. Milk was the significant source of selenium for pups and the selenium concentration in females' blood was reduced during lactation. The nursing period seemed to have the greatest impact on the mercury and selenium blood levels in examined seals. Natural development of the grey seal pup created an opportunity to decrease the levels of toxic substances obtained through the maternal transfer during foetal growth.

137Cs and 40K in gray seals Halichoerus grypus in the southern Baltic Sea.

This study presents levels of 137Cs and 40K concentrations in the placentas of seals gathered in the period 2007-2015. The mean activity of 137Cs and 40K was 5.49 Bq kg-1w.w. and 136.6 Bq kg-1 ww respectively. Statistically significant correlation was observed between the 137Cs activities in placenta and in herring-the staple food for seals. The concentrations of 137Cs and 40K were also determined in other tissues (muscle, liver, lung, and brain) of wild seals. The concentrations of 137Cs were from 2.59 Bq-1 ww (lungs) to 24.3 Bq kg-1 ww (muscles). The transfer factor values for 137Cs (seal tissue/fish) ranged from 0.89 to 2.42 in the case of the placentas and from 1.35 to 8.17 in the case of the muscle. For adults seal, the effective dose from 137Cs was 2.98 nGy h-1. The mean external radiation dose to pup was 0.77 nGy h-1 from 137Cs and 6.69 nGy h-1 from 40K.

Transfer of mercury and phenol derivatives across the placenta of Baltic grey seals (Halichoerus grypus grypus).

The placenta is an intermediary organ between the female and the developing foetus. Some chemical substances, including the most harmful ones, exhibit the ability to accumulate in or penetrate through the placenta. The aim of the study was to determine the role of the placenta of the Baltic grey seal (Halichoerus grypus grypus) in the transfer of endocrine disrupting compounds (EDCs) - (bisphenol A, 4-tert- octylphenol, 4- nonylphenol), as well as total and organic mercury. 30 placentas were collected from grey seals pupping under human care at the Hel Marine Station in the years 2007-2016. The assays were conducted using the technique of high-preformance liquid chromatography (phenol derivatives) and atomic absorption spectrometry (mercury and selenium). A measurable level of EDCs was indicated in the placentas of grey seals. It was established that the inorganic Hg form was accumulated in the placenta, and that its concentrations were an order of magnitude higher than the concentrations of the organic form, which penetrated to the foetus. Similar observations were made for phenol derivatives - bisphenol A, 4-tert- octylphenol and 4-nonylphenol. For this compound group the placenta was a barrier, but the properties of phenol derivatives suggest the possibility of their penetration through this organ.

Mercury in Feathers and Blood of Gulls from the Southern Baltic Coast, Poland.

Gulls were assessed as sentinels of contamination in the coastal zone of the Southern Baltic, research material being obtained from dead birds collected on Polish beaches and near fishing ports in 2009-2012. In feathers and blood of four gull species: herring gull (Larus argentatus), common gull (Larus canus), black-headed gull (Chroicocephalus ridibundus), and great black-backed gull (Larus marinus), concentration of total mercury (HgT) was assayed, taking into account the type of feathers, sex, and age. Stable isotopes (δ15N, δ13C) were used as tracers of trophic position in the food web. In the study, feathers and blood were compared as non-invasive indicators of alimentary exposure introducing mercury into the system. In order to do that, the correlations between mercury concentrations in the blood, feathers, and the birds' internal tissues were examined. The strongest relations were observed in the liver for each species R2Common Gull = 0.94, p = 0.001; R2Black-headed Gull = 0.89, p = 0.001; R2Great Black-backed Gull = 0.53, p = 0.001; R2Herring Gull = 0.78, p = 0.001. While no correlation was found with feathers, only developing feathers of juvenile herring gulls were found to be a good indicator immediate of exposure through food (R2muscle = 0.71, p = 0.001; R2kidneys = 0.73, p = 0.001; R2heart = 0.89, p = 0.001; R2lungs = 0.86, p = 0.001; R2brain = 0.83, p = 0.001). Additionally, based on studies of herring gull primary feathers, decrease of mercury concentration in the diet of birds over the last two decades is also discussed.

Inhalation - Route of EDC exposure in seabirds (Larus argentatus) from the Southern Baltic.

Despite the presence of endocrine disrupting mercury, PAHs, alkylphenols and bisphenol A in inhaled air, scientific literature lacks information on their penetration into the lungs. Large lung capacity in birds makes this route of penetration more significant than in other animals. The studies were conducted on lungs of herring gulls found in the Gulf of Gdansk area. The results were juxtaposed with other tissues, including the intestines, which reflect the main, alimentary penetration route of harmful substances into the organism. It was determined that the capacity of bird's lungs, affects the efficiency with which mercury is absorbed from the air. Birds found to have high mercury concentrations in lungs had low PAHs concentrations, what was determined by the fact that the birds foraged in two different areas, as well as on different trophic levels. The alimentary route of phenol derivatives into the organism was of greater significance than inhalation.

Asymmetric Synthesis of Isoquinoline Alkaloids: 2004-2015.

In the past decade, the asymmetric synthesis of chiral nonracemic isoquinoline alkaloids, a family of natural products showing a wide range of structural diversity and biological and pharmaceutical activity, has been based either on continuation or improvement of known traditional methods or on new, recently developed, strategies. Both diastereoselective and enantioselective catalytic methods have been applied. This review describes the stereochemically modified traditional syntheses (the Pictet-Spengler, the Bischler-Napieralski, and the Pomeranz-Fritsch-Bobbitt) along with strategies based on closing of the nitrogen-containing ring B of the isoquinoline core by the formation of bonds between C1-N2, N2-C3, C1-N2/N2-C3, and C1-N2/C4-C4a atoms. Methods involving introduction of substituents at the C1 carbon of isoquinoline core along with syntheses applying various biocatalytic techniques have also been reviewed.

Organochlorine contaminants in the muscle, liver and brain of seabirds (Larus) from the coastal area of the Southern Baltic.

The presence of persistent organic pollutants in the environment manifests itself most strongly in the marine trophic chain, where the highest link is comprised of seabirds. At the same time, seabirds are excellent indicators of contamination in their habitat. The present study concentrates on toxic substances: polychlorinated dibenzo-p-dioxin (PCDDs), polychlorinated dibenzofurans (PCDFs) and chlorinated organic pesticides (OCPs) accumulated in the livers, pectoral muscles and brains of dead gulls collected along the Polish coast of the Baltic Sea in the years 2010-12. The highest toxic equivalence was determined in the livers of Larus argentatus (TEQ(birds TEF)-28.3pgg(-1) ww) and Larus marinus (TEQ(birds TEF)-29.9pgg(-1) ww.). However, the toxic equivalence of muscles was lower and amounted to 3.9pgg(-1) ww. and 7.8pgg(-1) ww. respectively for the two species. The lowest toxic equivalence was found in the brains of birds, where only one, the most toxic, 2,3,7,8 TCDD congener was found (TEQ(birds TEF) 0.87pgg(-1) ww). The highest concentration of chloroorganic pesticides was determined in the brains of the birds (total OCP 167.8pgg(-1) ww.), lower concentrations were found in the livers (total OCP 92.1pgg(-1) ww.) and muscles (total OCP 43.1pgg(-1) ww.). With regard to pesticides, the highest proportion in the total OCP content was constituted by DDT and its isomers (liver 81%, muscles 77% and brain 55%). High concentrations of the studied pollutants in the livers of gulls found dead on the coast of the Southern Baltic could have been effected by levels of contamination in the birds' last meals, which resulted in a seven-fold increase of the liver's toxic equivalence and a two-fold increase in OCP concentration in relation to muscles.

Species differences in total mercury concentration in gulls from the Gulf of Gdansk (Southern Baltic).

Aquatic birds occupy a high position in the trophic pyramid of the Baltic Sea. This means that they accumulate the greatest amount of harmful substances, including mercury, in their bodies. This element penetrates into their systems mainly via the alimentary canal. The amount of mercury absorbed from food depends on how badly the environment is polluted with this metal. The aim of this study was to discover the concentrations of total mercury (HgT) in the contour feathers, muscles, brain, lungs, liver, kidneys, heart and blood of four gull species Herring Gull (Larus argentatus), Common Gull (Larus canus), Black-headed Gull (Larus ridibundus) and Great Black-backed Gull (Larus marinus) and organic mercury (Hgorg) in the liver and brain of Herring Gull. The most important characteristic of the results obtained for the studied gulls was the statistically significant differences between the four species, probably resulting from their different diets-confirmed by stable-isotopes analysis (δ(15)N and δ(13)C). A logarithmic dependence was found between HgT in the blood and HgT in the brain of the Herring Gull. The authors suggest that among gulls burdened with the greatest mercury load, it is possible that the brain is protected by higher Hg accumulation in the muscles. The percentage share of Hgorg in the brain and liver of the Herring Gull depended on the concentration of HgT in these tissues and was always higher in the brain. In none of the cases, did the mercury levels assayed in the internal gulls' tissues exceed values associated with adverse health effects.

Chlorinated herbicides in fish, birds and mammals in the Baltic Sea.

The aim of the present work was to determine the concentration levels, as well as accumulation and magnification coefficients, of triazine derivatives in herring gulls and Baltic grey seals 11 years after a ban on their use in the EU and eight after their exclusion in Poland. Dead birds were collected in the coastal zone of the Gulf of Gdansk in the years 2010-2012. The grey seals, on the other hand, were from before 2007, when s-triazine derivatives were still in use. Triazine herbicides (atrazine, simazine, propazine, terbutrine, prometrone, prometrine and ametrine) were found in the muscles and livers of birds and mammals and also in fish. The obtained results indicated the presence of all the assayed triazines in whole Baltic herring and their livers, while fish muscles were found to be free of prometrone and ametrine. In the muscles and liver of the grey seal, no ametrine, propazine or terbutrine were found, while prometrine was found in the liver of only one specimen. Research showed that simazine did not accumulate and magnify in marine birds and mammals. Atrazine became accumulated in the liver of birds and mammals while magnification was determined in their muscles. The accumulation of ametrine was found in the muscles of seals.

Mercury in the eggs of aquatic birds from the Gulf of Gdansk and Wloclawek Dam (Poland).

The aim of this paper was to assess the influence of diet on the concentrations of total mercury (HgTOT) in the eggs of aquatic birds. Trophic level was determined using stable isotopes (δ(15)N, δ(13)C). Analysis was carried out on eggs (laid in 2010-2012) belonging to two species of terns nesting at the River Vistula outlet on the Gulf of Gdansk and on herring gulls nesting both in Gdynia harbour and on the Vistula dam in Wloclawek. The results show that seafood diet causes the highest load of mercury, that which is transferred into terns eggs. The amounts of accumulated mercury obtained were found to be different in the particular egg components with Hgalbumen > Hgyolk > Hgmembrane > Hgshell. In the herring gull eggs, three stages of embryo development with varying levels of mercury were determined. It was observed that mercury received from the albumen and yolk was most effectively removed when developing embryo into down.

Density functional theory calculations of the optical rotation and electronic circular dichroism: the absolute configuration of the highly flexible trans-isocytoxazone revised.

Ab initio calculations of the optical rotation (OR) and electronic circular dichroism (ECD) for a series of trans-diastereomers of the natural cytokine modulator cytoxazone 1-4 have been performed by density functional theory (DFT). The calculation of OR and ECD curves provides, after critical assessment, a reliable method for the assignment of absolute configuration of these conformationally flexible molecules. The effects of the level of theory used for calculations, changes of conformer equilibrium, and the solvent influence on the geometry and values of calculated OR data are discussed, leading to the conclusion that the most frequently used B3LYP/6-31G(d) method is not adequate for prediction of the absolute configuration of this type of highly flexible molecules. The absolute configurations of levorotatory trans-isocytoxazone 2 and analogues 1, 3, and 4 have been established as (-)-(4S,5S)-trans-1-4; i.e., it is in opposition to the previously published configuration (-)-(4R,5R)-trans-2.