Jump to content


Senior Members
  • Posts

  • Joined

  • Last visited

Posts posted by BabcockHall

  1. We have a tertiary-butyl protected amino acid in which nitrogen is protected with FMOC.  We removed the FMOC group with diethyl amine, and we used rotary evaporation plus a toluene strip to remove the volatiles.  We attempted to purify over a short column of silica.  We were able to remove a fast-moving impurity (presumably dibenzofulvene or a derivative) using 40:60 EtOAc/hexanes, then switched to 99:1 hexanes/TEA in the hope of eluting the N-deprotected product, still bearing the carboxylate protecting group, but the product was not soluble in EtOAc or in DCM (it might have been a suspension).  We eluted with 90:10 DCM/methanol and saw two products by TLC.  They were not completely separated.  I am interested in soliciting ideas for what we should do differently next time.

    In retrospect a lower percentage of methanol would have been an improvement.  I wonder whether or not the solubility of the amine would have been better in chloroform than it was in DCM.  I realize that some people do not purify at all at this stage, but instead couple the crude product with another amino acid.  We also want to couple to another amino acid. 

  2. https://doi.org/10.1002/chem.201101163

    I am working on synthetic routes to a glucoside.  The beta-trimethylsilylethoxymethyl (SEM) group has some attractive features (particularly in regards to deprotection), but I have only found one paper in which four SEM groups were used to protect the oxygen atoms at carbons 2-4 and 6 of a glycoside conjugated with a steroid.  They did not deprotect to the best of my knowledge, but I assume that one would use a standard recipe.  I did find a paper in which a glycoside was protected with several different groups, including one SEM.  Are there disadvantages to using the SEM group as the protecting group?  Are there reasons why it has been used more in carbohydrate chemistry?  Should I be favoring other protecting groups instead?

  3. Our interest is in LC/MS of the peptides, and we plan to work in water/acetonitrile/formic acid.  We found a number of protocols for C-18 on line (I can provide links to these), and we are focusing on those protocols that specify formic acid (not TFA).  Our Zip Tips use C-18.  (1) Are Zip Tips necessary?  (2) Given their capacity, does one obtain enough for material for one or for several LC/MS runs?  (3) Are Zip Tips reusable? (4) Does anyone have a paper or protocol that is especially informative?  Thank you very much.

  4. I don't know the answer to your question, but I am inclined to say that we will try to optimize the compounds.  With regard to these compounds, we have in vitro data against a validated target enzyme.  They are irreversible inhibitors with ligand binding efficiencies greater than 0.3.  The second generation inhibitors that we are currently synthesizing were designed with transport across membranes as a consideration.

  5. The enzyme has been shown to be essential in some pathogenic bacterial strains and also in Candida albicans.  We are in the process of revising our first manuscript on our inhibitors.  For the best compounds in this series, the ratios of binding energies to molecular weights are promising, among other possibly favorable properties.  We envision either an antifungal or antibacterial compound, although at the moment we are more fungal-focused.

    What sort of near-term commercial applications do you mean?

  6. That is a helpful reference; thank you.  We synthesized a family of compounds that are good inhibitors of an essential microbial enzyme.  As a whole they are not very water-soluble, although there is variation in the group.  One of the more hydrophilic ones is one of two that showed growth inhibition.  Therefore, we are synthesizing the next generations of inhibitors that might be more water-soluble and thinking about what are the meanings of various test results.

  7. "VAERS cannot prove that a vaccine caused a problem. Specifically, a report to VAERS does not mean that a vaccine caused an adverse event. But VAERS can give CDC and FDA important information. If it looks as though a vaccine might be causing a problem, FDA and CDC will investigate further and take action if needed."

    "In some cases, multiple reports are submitted for the same adverse event."

    "VAERS data alone cannot determine if the vaccine caused the reported adverse event.

    This specific limitation has caused confusion about the publicly available data, specifically regarding the number of reported deaths. In the past there have been instances where people misinterpreted reports of death following vaccination as death caused by the vaccines; that is a mistake."

    These three quotes about the vaccine adverse events reporting system come from the CDC.  


    Politifact or some other fact-checking organization also had an article about this kind of erroneous interpretation, if I recall correctly.

    The Economist magazine calculated an estimate of worldwide excess deaths, of 10 million people.  The CDC has a table broken down by age at this link.  https://www.cdc.gov/coronavirus/2019-ncov/covid-data/investigations-discovery/hospitalization-death-by-age.html

    "Sample interpretation: Compared with 5—17-year-olds, the rate of death is 45 times higher in 30—39-year-olds and 8,700 times higher in 85+-year-olds."

  8. "Two doses of BNT162b2 are highly effective across all age groups (≥16 years, including older adults aged ≥85 years) in preventing symptomatic and asymptomatic SARS-CoV-2 infections and COVID-19-related hospitalisations, severe disease, and death, including those caused by the B.1.1.7 SARS-CoV-2 variant. There were marked and sustained declines in SARS-CoV-2 incidence corresponding to increasing vaccine coverage. These findings suggest that COVID-19 vaccination can help to control the pandemic."  From a study of the  Pfizer vaccine in Israel, published earlier this month in The Lancet.

    "This study in a nationwide mass vaccination setting suggests that the BNT162b2 mRNA vaccine is effective for a wide range of Covid-19–related outcomes, a finding consistent with that of the randomized trial."  From a study published in April, in the New England Journal of Medicine.

    There was an article at CNN that quoted some hematologists, all of whom recommended that people get the vaccine.

  9. Hello Everyone, I am making enzyme inhibitors and turning them over to a microbiology laboratory for testing against standard strains of bacteria and fungi.  They are performing disk diffusion assays, and seeing a few results that look positive.  I would like better to understand the meaning and limitations of this experiment.  I would hazard a guess that the compound's concentration falls off at greater distances from the disk, but I don't know how to interpret the diameter of the dead zone in a quantitative way, or even if that is possible.  Perhaps there is a good textbook treatment of this subject, for example.

  10. I can't say which transition state without knowing the other reactants besides oxygen.  Let me limit myself to nucleophilic substitution reactions for the sake of illustration.  By an open transition state I mean one in which the leaving group has largely left (the bond order to the central atom might be roughly 0.2) and the nucleophile is only weakly present (bond order also might be around 0.20).  The opposite situation (a tight transition state) is one in which the leaving group has just begun to depart (bond order of 0.8 or so) and the nucleophile has largely made a bond to the central atom.

  • Create New...

Important Information

We have placed cookies on your device to help make this website better. You can adjust your cookie settings, otherwise we'll assume you're okay to continue.