Synthesis of methyl (5Z,8Z,10E,12E,14Z)-eicosapentaenoate

The first total synthesis of methyl (5Z,8Z,10E,12E,14Z)-eicosapentaenoate has been achieved in seven steps and in 16% overall yield. The synthesis confirmed the assigned structure of this polyunsaturated natural product.     

Resolving Inflammation: Synthesis,Configurational Assignment,and Biological Evaluations of RvD1n−3 DPA

New drugs that can resolve inflammation without immunosuppressive effects are at the medicinal chemistry frontier. Pro-resolving endogenously formed small molecules, that is, the resolvins, are excellent candidates displaying such bioactions. The first total synthesis of the specialized pro-resolving mediator RvD1_{n−3 DPA} has been achieved using the underutilized sp³–sp³ Negishi cross coupling reaction and an alkyne hydrosilylation–protodesilylation protocol. Biological evaluations revealed that this novel mediator displays low nanomolar pro-resolving properties and potently activates the human DRV1/GPR32 receptor. As such, this endogenous natural product is a lead compound for the development of novel immunoresolvents.     

Stereoselective Synthesis,Configurational Assignment and Biological Evaluations of the Lipid Mediator RvD2n-3 DPA

Herein we report the first total synthesis of RvD2_{n-3 DPA}, an endogenously formed mediator biosynthesized from the omega-3 fatty acid n-3 docosapentaenoic acid. The key steps are the Midland Alpine borane reduction, Sonogashira cross-coupling reactions, and a Z-selective alkyne reduction protocol, yielding RvD2_{n-3 DPA} methyl ester in 13 % yield over 12 steps (longest linear sequence). The physical property data (UV chromophore, chromatography and MS/MS fragmentation) of the synthetic lipid mediator matched those obtained from biologically produced material. Moreover, synthetic RvD2_{n-3 DPA} also carried the potent biological activities of enhancing macrophage uptake of Staphylococcus aureus and zymosan A bioparticles.     

Synthesis of 1,3-dithianes and 1,3-dithiolanes. Baker's yeast reduction and lipase-catalyzed resolution for synthesis of enantiopure derivatives.

Three 1,3-dithiolanes and four 1,3-dithianes have been synthesised from 1-(1,3-dithiolan-2-yl)-2-propanone and 1-(1,3-dithian-2-yl)-2-propanone, respectively. Asymmetric reductions of these ketones using baker's yeast gave the corresponding enantiopure (S)-alcohols. Baker's yeast also reduced the double bond in 3-(1,3-dithian-2-yl)-3-buten-2-one enantioselectively to give (S)-3-(1,3-dithian-2-yl)-2-butanone. 3-(1,3-Dithian-2-yl)-3-buten-2-one was also reduced chemo-selectively and the resulting 3-(1,3-dithian-2-yl)-3-buten-2-ol was resolved by transesterification in organic solvent using lipase B from Candida antarctica to yield the (S)-alcohol and the (R)-acetate with very high enantiomeric ratio, E. Racemic 1-(1,3-dithiolan-2-yl)-2-propanol and 1-(1,3-dithian-2-yl)-2-propanol were also resolved under similar conditions to give the (S)-alcohols and the corresponding (R)-acetates.     

Syntheses of some polyunsaturated sulfur- and oxygen-containing fatty acids related to eicosapentaenoic and docosahexaenoic acids.

With the aim of enhancing selectively the beneficial biological effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) a number of polyunsaturated fatty acids containing sulfur or oxygen atoms in the chain has been synthesized starting from EPA and DHA, respectively. Oxidative degradation of these acids led to the corresponding aldehydes all-(Z)-3,6,9,12-pentadecatetraenal and all-(Z)-3,6,9,12,15-octadecapentaenal. Reactions with DBU converted these aldehydes quantitatively into the conjugated isomers (2E,6Z,9Z,12Z)-pentadecatetraenal and (2E,6Z,9Z,12Z,15Z)-octadecapentaenal, respectively. The four aldehydes were transformed by a sequence of reactions comprising reduction to the alcohols, halogenation and substitution with mercapto esters into the corresponding sulfur containing polyunsaturated fatty acid esters. The oxygen containing esters were prepared from the respective alcohol by boron trifluoride catalysed reaction with ethyl diazoacetate.     

Aluminium in tea—concentrations, speciation and bioavailability

Tea (Camellia sinensis) is one of a few plants accumulating aluminium (Al), making tea a major source of dietary Al intake. This paper reviews published studies on the concentrations, speciation and bioavailability of Al in tea. With very few exceptions, the total concentration of Al in tea infusions is in the range 1-6 mg l⁻¹. Probably more than 90% of this Al is bound to organic matter, but the nature of the organic species is unclear. Three studies using size exclusion chromatography provide evidence for Al species in the molecular mass (MM) range 4000-8500 Da, probably polyphenolic complexes. Two ultrafiltration studies indicate the presence of Al species with MMs above 10,000. The relative amount of the different organic Al species in tea infusions is unclear, and even the identity of any of these has not been demonstrated with certainty. A possible exception is Al trioxalate, which may be an important species based on evidence from two ²⁷Al-NMR studies. It seems fairly well established that drinking tea leads to measurable, but moderate increases in urinary Al excretion. However, the Al present in tea does not seem to be much more bioavailable than that from other dietary sources. Even so, it cannot be dismissed that tea infusions may contain particularly bioavailable and neurotoxic compounds such as Al maltolate, but this is at present speculative.     

Synthetic efforts towards the protoilludenes. A formal synthesis of Δ-protoilludene

An improved route to 5,8,8-trimethylbicyclo[4.3.0]-4-nonen-3-one, a key intermediate for the synthesis of the protoilludane skeleton and in particular Δ⁷-protoilludene, is reported. Attempts on an alternative synthesis of Δ⁶-protoilludene based on a phenylsulfonyl allene cycloaddition reaction is also presented.     

Synthesis of methoxy-substituted phenols by peracid oxidation of the aromatic ring

[reaction: see text] A novel benign protocol for the preparation of hydroxy-methoxybenzene derivatives is disclosed. By utilizing this protocol, activated aromatic compounds such as 1,3-dimethoxy-2-methyl-benzene and 1-(2,6-dimethoxyphenyl)ethanone are smoothly converted to the corresponding monohydroxylated compound. The reaction can be considered to be a normal aromatic electrophilic substitution reaction, and the regioselectivity for the reaction thus follows the similar rules as for electrophilic substitutions. The protocol is composed by benign reagents, namely, hydogenperoxide, acetic acid, and p-toluene sulfonic acid, which lead to the production of ethaneperoxoic acid in situ. The ethaneperoxoic acid operates as the hydroxylating reagent. The hydroxylation reaction is completed within a short period and requires moreover only mild experimental conditions, which make this novel protocol a green, cheap, and rapid process leading to hydroxy-methoxybenzene derivatives. The proposed reaction mechanism is supported by density functional theory and NMR spectroscopy experiments. The mechanism is constituted by two discrete steps: (a) addition of OH+ to the most nucleophilic carbon atom of the aromatic ring, which is the rate-determining step, and (b) the loss of the proton from the aromatic ring.     

Iteration of transmit-beam aberration correction in medical ultrasound imaging

Simulations of iterative transmit-beam aberration correction using a time-delay and amplitude filter have been performed to study the convergence of such a process. Aberration in medical ultrasonic imaging is usually modeled by arrival-time and amplitude fluctuations concentrated on the transducer array. This is an approximation of the physical aberration process, and may be applied to correct the transmitted signal using a time-delay and amplitude filter. Estimation of such a filter has proven difficult in the presence of severe aberration. Presented here is an iterative approach, whereby a filter estimate is applied to correct the transmit-beam. This beam induces acoustic backscatter better suited for arrival-time and amplitude estimation, thus facilitating an improved filter estimate. Two correlation-based methods for estimating arrival-time and amplitude fluctuations in received echoes from random scatterers were employed. Aberration was introduced using eight models emulating aberration produced by the human abdominal wall. Results show that only a few iterations are needed to obtain corrected transmit-beam profiles comparable to those of an ideal aberration correction filter. Furthermore, a previously developed focusing criterion is found to quantify the convergence accurately.     

The management of high seas fisheries

The intergovernmental United Nations Conference on Highly Migratory and Straddling Stocks, initiated in 1993 and finished in 1995, addressed the conservation and management of fishery resources located both within the coastal state 200 mile Exclusive Economic Zone (EEZ) and the adjacent high seas. These types of marine resources continue to be a source for international conflicts and debates. The original United Nations Law of the Sea of 1982 failed to address transboundary fisheries in a proper way. In particular, the agreement did not recognize the emergence of the complicated straddling stock issue. In the new United Nations Law of the Sea agreement of 1995, a consensus was reached that the management of the straddling and highly migratory fish stocks should be carried out through regional fisheries management organizations. We present a review of the straddling stock issues in the international agreement emerging from the negotiations within the United Nations. The review is contrasted with and clarified by game theoretic analyses. We also discuss one international fishery exemplifying the case, the Norwegian springspawning herring. The main conclusion is that the local problems, faced during the stage of setting up regional fisheries organizations for the management of straddling and highly migratory fish stocks, are expected to be much more complicated and difficult to solve as compared to the cases of shared fish stocks. In the current paper, we present two reasons for this increased complexity. The first is the larger number of players as compared to the case of shared fish stocks and the second is the possibility of new members entering the regional fisheries organizations.