Casualties caused by organophosphorus pesticides are a burden for health systems in developing and poor countries. Such compounds are potent acetylcholinesterase irreversible inhibitors, and share ...the toxic profile with nerve agents. Pyridinium oximes are the only clinically available antidotes against poisoning by these substances, but their poor penetration into the blood-brain barrier hampers the efficient enzyme reactivation at the central nervous system. In searching for structural factors that may be explored in future SAR studies, we evaluated neutral aryloximes as reactivators for paraoxon-inhibited Electrophorus eel acetylcholinesterase. Our findings may result into lead compounds, useful for development of more active compounds for emergencies and supportive care.
The synthesis of a stable ketene aminal phosphate (α-phosphoryloxy enecarbamate) derived from
N,
N-diprotected acetamide, bearing two different removable protecting groups, is disclosed. This ...synthetic intermediate underwent successful palladium-catalyzed cross-coupling reactions to afford functionalized enynes and dienes.
Despite the availability of alternative methods for drying tetrahydrofuran (THF), the use of the still apparatus, wherein a THF solution containing Na-bezophenone ketyl is heated to reflux, remains ...widespread. We herein propose a set of procedures to solve the problems usually faced in applying this drying technique. Moreover, a discussion is made on the chemical knowledge underlying such procedures. Safety and economy issues concerned with the operation of the THF still apparatus are also discussed.
A ligand-free Suzuki–Miyaura reaction for the cross-coupling of aryl halides with aryl boronic acids has been developed utilizing polyethylene glycol 300 (PEG 300) and Pd
2(dba)
3 0.01%. This system ...afforded the corresponding cross-coupled products in good to excellent isolated yields and TONs after a simple workup.
In this work, we present ligand-free Suzuki cross-coupling reactions in PEG 300 under thermal conditions at 55
°C with good yields of conversion; better results were obtained with low reaction time. In 1 hour, 1-iodo-4-nitrobenzene and phenylboronic acid reached 98% of the yield and 9700 of TON. Better results were obtained with Pd(0) sources. The reaction system was recycled up to three times with good activity.
Edunol (
3), a pterocarpan isolated from
Harpalyce brasiliana, a plant used in the northeast of Brazil against snakebites, was obtained by synthesis and showed antimyotoxic, antiproteolytic and PLA2 ...inhibitor properties. These proprieties could be improved through the synthesis of a bioisoster (
5), where the prenyl group was replaced by the benzyl group.
Edunol (
3), a pterocarpan isolated from
Harpalyce brasiliana, a plant used in the northeast of Brazil against snakebites, was obained by synthesis and showed antimyotoxic, antiproteolytic and PLA2 inhibitor properties. These proprieties could be improved through the synthesis of a bioisoster (
5), where the prenyl group was replaced by the benzyl group.
Nine other cases. A successful reaction relying on substoichiometric tin (∼0.15
mol
equiv) is also reported.
A direct selective protection (O-benzylation) of two or more hydroxyl groups in polyols ...displaying diverse structural patterns was made possible by the establishment of conditions that enable an efficient turnover for the Bu
2Sn group, initially at the corresponding stannylene acetals (only ∼1.0
mol
equiv of Bu
2SnO was employed). It was also demonstrated that one might exert control over the number of protected groups, by means of appropriate tuning of reaction conditions. The feasibility of a substoichiometric (tin source) catalytic protocol was demonstrated as well.
(±)-1,2-O-Isopropylidene-3,6-di-O-benzyl-myo-inositol is a relevant starting material in the synthesis of inositol phosphates and their analogs. In this study, we disclose our efforts toward an ...efficient methodology for the kinetic resolution of this compound by lipase B of Candida antarctica (Novozym 435). This reaction selectively affords L-(−)-1,2-O-isopropylidene-5-O-acetyl-3,6-di-O-benzyl-myo-inositol. From a conversion of 34% with EtOAc as an acylating agent, the use of vinyl acetate increased the yield to over 49%, while maintaining a very high ee (>99%). The combination of the latter reagent with TBME as a solvent accelerates the reaction.
This paper shows the production of lipase B from
Candida antarctica
(LIPB) after cloning the gene that encoded it in
Pichia pastoris
using PGK as a constitutive promoter. The production of the lipase ...is lower using this strategy but it avoids the use of inducers like methanol. The performance of this enzyme was compared with that of the commercial enzyme (CALB) after immobilization on different supports in different reactions. As supports, we used Accurel 1000, and three core-shell supports (poly(methyl methacrylate) on the core and on the shell - PMMA/PMMA; poly(methyl methacrylate-
co
-divinylbenzene) on the core and on the shell - PMMA-
co
-DVB/PMMA-
co
-DVB; and poly(styrene-
co
-divinylbenzene) on the core and on the shell - PS-
co
-DVB/PS-
co
-DVB). The popular Novozym 435 was also utilized to assess the features of the new biocatalysts. All these supports adsorbed lipases
via
interfacial activation of the open form of the lipase on the hydrophobic surface of the supports. The studied reactions were esterification of oleic acid and ethanol in a solvent-free medium, resolution of (±)-1,3,5-
O
-benzyl-
myo
-inositol
via
acylation using vinyl acetate in hexane and resolution of (±)-1,2-
O
-isopropylidene-3,6-di-
O
-benzyl-
myo
-inositol
via
acylation using vinyl acetate (solvent free system). The results varied depending on the employed supports and on the studied reactions, but some general trends may be observed, pointing to better behavior of LIPB compared to CALB. The use of 4 different supports gave more strength to these differences, as it did not depend on a specific difference between a single support/enzyme pair, but it is more general. Thus, LIPB seems to have some advantages compared to the commercial enzyme on all the reactions assayed in this paper. PS-
co
-DVB/PS-
co
-DVB-LIPB is in general the most active preparation (even 50% higher activity was observed). Further investigations are in development to determine the structural reasons for these differences.
This paper shows the production of lipase B from
Candida antarctica
(LIPB) after cloning the gene that encoded it in
Pichia pastoris
using PGK as a constitutive promoter. The lipase was immobilized on different home-made supports for distinct reactions.
Chronic eosinophilic rhinosinusitis with nasal polyps (CRSwNP eosinophilic) is characterised by the formation of benign and bilateral nasal polyps. We aimed to compare the effectiveness of ...azithromycin as an immunomodulator with the use of a placebo in patients presenting with CRSwNP concomitant with asthma and aspirin intolerance after 3 months of treatment and at a 1-year follow-up.
We performed a randomised, double-blind, placebo-controlled trial. Patients received 500 mg azithromycin orally three times/week for 12 weeks. Improvement was evaluated by staging, the Sino-Nasal Outcome Test (SNOT-22), and nasal polyp biopsy. Data collected at pretreatment and 3 months posttreatment were compared. Quality of life was evaluated at the 1-year follow-up.
Twenty-seven and 21 patients were treated with azithromycin and a placebo, respectively. The medication was well tolerated overall. Twenty patients (74%) in the azithromycin group and three patients (14%) in the placebo group were not refer- red for surgery at the end of the 3-month treatment. Regarding subjective improvement, there was a median decrease only in the azithromycin group, and the between-group difference was significant. SNOT-22 improvement was maintained in the azithromy- cin group at the 1-year follow-up.
Azithromycin could be considered a therapeutic option for patients presenting with CRSwNP concomitant with asthma and aspirin intolerance.
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