A series of 33 quinoline derivatives have been synthesized and evaluated for their in vitro antibacterial activity against
Mycobacterium tuberculosis H
37Rv using the Alamar Blue susceptibility test ...and the activity expressed as the minimum inhibitory concentration (MIC) in μg/mL. Compounds
5e and
5f exhibited a significant activity at 6.25 and 3.12
μg/mL, respectively, when compared with first line drugs such as ethambutol and could be a good starting point to develop new lead compounds in the fight against multi-drug resistant tuberculosis.
A series of 33 quinoline derivatives have been synthesized and evaluated for their in vitro antibacterial activity against
Mycobacterium tuberculosis H
37Rv using the Alamar Blue susceptibility test and the activity expressed as the minimum inhibitory concentration (MIC) in μg/mL. Compounds
5e and
5f exhibited a significant activity at 6.25 and 3.12
μg/mL, respectively, when compared with first line drugs such as ethambutol and could be a good starting point to develop new lead compounds in the fight against multi-drug resistant tuberculosis.
(R)‐Propylene carbonate is an important intermediate in the synthesis of tenofovir pro‐drugs such as tenofovir alafenamide fumarate (TAF) and tenofovir diisoproyl fumarate (TDF). Independent of the ...pro‐drug type, tenofovir presents a chiral secondary hydroxy derivative, which can be obtained directly from (R)‐propylene carbonate. Herein, we report our chemo‐enzymatic continuous‐flow strategy towards (R)‐propylene carbonate starting from a very cheap and renewable raw material, glycerol. We were able to synthesize (R)‐propylene carbonate in seven continuous‐flow steps, starting from glycerol, in good‐to‐excellent yields (66–93 %) and excellent selectivity (E > 200).
(R)‐Propylene carbonate is an important intermediate in the synthesis of tenofovir alafenamide fumarate (TAF) and tenofovir disoproxil fumarate (TDF) from glycerol. TAF and TDF present a chiral secondary hydroxy derivative, which can be obtained by a seven‐step chemo‐enzymatic continuous‐flow strategy that yields (R)‐propylene carbonate in good‐to‐excellent yields and excellent selectivity.
Chiral myo‐inositol derivatives play key roles in cell‐signaling processes. Despite the relevance of these compounds, few syntheses of them rely on enantioselective catalytic reactions. Even fewer ...reports describe the use of desymmetrization of myo‐inositol derivatives. In fact, most routes involve resolution by derivatization. Thus, a symmetrical partially protected myo‐inositol derivative, 1,3‐di‐O‐benzyl‐myo‐inositol (1), was used as a substrate in fast lipase‐catalyzed desymmetrization reactions. Among the lipases tested, both Lipozyme RM‐IM and Lipozyme TL‐IM were effective in catalyzing the formation of the chiral acetate l‐(+)‐6‐O‐acetyl‐1,3‐di‐O‐benzyl‐myo‐inositol l‐(+)‐2 with high conversion (98–99 %) and ee (>99 %). Conversely, Novozyme 435 and Lipomod 34P as biocatalysts showed different regioselectivity, leading to the formation of the symmetrical 5‐O‐acetylated product. We were able to reuse TL‐IM lipase seven times without any noticeable decrease in the conversion. Acetate l‐(+)‐2 is a potential precursor of biologically active myo‐inositol derivatives and other relevant materials for cell biology studies.
Depending on the choice of lipase, 1,3‐di‐O‐benzyl‐myo‐inositol (1) either undergoes desymmetrization to form l‐(+)‐6‐O‐acetyl‐1,3‐di‐O‐benzyl‐myo‐inositol (with Lipozyme RM‐IM or Lipozyme TL‐IM), or is transformed into the meso 5‐O‐acetyl derivative 3 (with Novozym 435).
A series of twenty-one quinoline derivatives have been synthesized and evaluated against
Mycobacterium tuberculosis. Three compounds exhibited a significant activity (2.5
μg/mL), which can be ...compared with that of the first line drugs, ethambutol (3.12
μg/mL) and rifampicin (2.0
μg/mL).
A series of twenty-one 7-chloro-4-quinolinylhydrazones (
3a–
u) have been synthesized and evaluated for their in vitro antibacterial activity against
Mycobacterium tuberculosis H
37Rv. The compounds
3f,
3i and
3o were non-cytotoxic and exhibited an important minimum inhibitory concentration (MIC) activity (2.5
μg/mL), which can be compared with that of the first line drugs, ethambutol (3.12
μg/mL) and rifampicin (2.0
μg/mL). These results can be considered an important start point for the rational design of new leads for anti-TB compounds.
myo-Inositol derivatives bearing selectively protected hydroxyl groups are relevant precursors of high-value myo-inositols. In the present study, we applied the response surface method to the ...optimization of kinetic resolution of (±)-1,3,6-tri-O-benzyl-myo-inositol by Novozym 435 (immobilized lipase B from Candida antarctica) with vinyl acetate in hexane. Reaction temperature, substrate, acyl donor and enzyme concentrations were set as variables. Through the constructed mathematical model, optimum condition for this enzymatic condition was established. The feasibility of enzyme recycle was demonstrated.
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► Biocatalysis under continuous flow conditions. ► Lipase catalyzed kinetic resolutions. ► Myo-inositol derivatives. ► Recyclability of immobilized lipases under continuous flow ...conditions.
In this work, we have investigated the biocatalytic continuous flow process with a packed-bed reactor for the kinetic resolution of (±)-1,3,6-tri-O-benzyl-myo-inositol ((±)-1) by alcoholysis using Novozym 435. Excellent conversions and stereselectivities were attained in short reaction time. We found that this enzymatic transformation under continuous flow in TBME with vinyl acetate (10:1 ratio with (±)-1) at 50°C, with a 3min-residence time secured the best results (50% conversion and eep>99%). The feasibility of a continuous operation of the Novozym 435-containing-packed-bed reactor over a longer period of time was demonstrated via a 9-cycle experiment wherein the lipase remained stable.
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.
Sterically hindered myo-inositol derivatives were assayed against different commercial lipases. It was found that dl-1,3,6-tri-O-benzyl-myo-inositol undergoes efficient kinetic resolutions mediated ...by Pseudomonas sp. lipases (PS-C, PS-IM) and CaLB (Novozym 435). Under the best conditions, the O-acylated l-enantiomorph was obtained in up to >99% ee with conversions of up to >49%. Differences in the immobilization support of the Pseudomonas sp. lipases had a marked effect on their resolution performance.
Human tuberculosis (TB) is caused by members of the Mycobacterium tuberculosis complex (MTBC), including Mycobacterium tuberculosis var. tuberculosis (MTB) and Mycobacterium tuberculosis var. ...africanum (MAF). While MTB is isolated worldwide, MAF is almost completely restricted to the African continent, and despite the historical proximity between Brazil and Africa during the slave trade, no case of TB being caused by MAF has been reported in Brazil to date. We hereby describe the first case of TB caused by MAF in Brazil comparing its genome against the published ones. A female patient who had never visited Africa presented with clinical symptoms typical of pulmonary TB. Based on 16S rRNA gene sequencing, the cultured isolate was identified as belonging to MTBC and partial sequence of the hsp65 gene was identical to that of MAF. This was confirmed by genotyping based on detection of Single Nucleotide Polymorphism (SNP), Region of Difference (RD) and spoligotyping. The isolate presented the Shared International Typing (SIT) 181. In the whole-genome comparison against MAF genomes available on published EMBL-EBI European Nucleotide Archive (ENA), the Brazilian genome (MAFBRA00707) was identified as belonging to Lineage 6 and clustered with isolates from The Gambia. This is the first report of the isolation of MAF from a patient from Brazil, without evidence of having any contact with an African index case.
•First case of tuberculosis caused by MAF in Brazil.•Extensive genotyping identification of the isolate.•Discussion of lack of detection of MAF due to incorrect procedures.•Close phylogenomics relationship with MAF isolated from The Gambia.
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