Archive for the ‘synthesis’ Category

August 13, 2007

August 13, 2007

The summer will be winding down soon and I am hoping to get back on track with posting.

There is an interesting paper from David Milstein (Weizmann Institute of Science) in the August 10th issue of Science describing the synthesis of amides from alcohols and amines. The method employs a special Ruthenium catalyst that effects the removal of two equivalents of H2, as shown below, in order to form the amide group. What makes this method attractive is that it requires only a small amount of catalyst, 0.1 mol%, and is stoichiometric for both the alcohol and amine starting materials. Nonetheless, it might be hampered by the fact that the catalyst must be handled under strictly controlled Argon-atmosperic conditions (Glove box) and so far has only been demonstrated on millimolar scale reactions.

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April 14, 2007

April 14, 2007

These are a little overdue… 

Word(s) of the week…Stem cells 

Here in the US Stem Cells have been in the headlines lately. Not the science of stem cells but the politics of stem cells and we in the pharma community have had front row seats on the debate.

On the right, we have politicos such as George Bush and the religious-right who take the position that human embryonic stem cells should be considered “human life” and manipulating these cells for the sake of knowledge violates the “sanctity” of life.  Furthermore, using the ‘slippery slope’ argument the religious groups fear that any use of tissue obtained from abortions would in effect perpetuate the procedure by making it a ‘nessicity’. Therefore, under the current administration the federal government is prohibited from funding stem cell research.

On the other side, we have scientists and patient rights advocates who scoff at the notion that stem cells should be considered “sacred” and view their opponents as being overzealous and major obstacles to the potential treatments of a number of debilitating diseases.

In my opinion, I think both sides are guilty of manipulating the truth to make their point, but being a scientist I am most concerned with the message being put forth by those in favor of stem cell research..I believe we have gone too far in exalting the potential of stems cells to provide cures for such a wide number of diseases in such a short time frame. While I am still young, I have been in the pharma field long enough to know hype when I see it. In my opinion any potential therapy involving stem cells will be decades away if not longer and will likely be successful for only a small set of diseases…Just look how long it took for monoclonal antibodies to make it onto the market…almost 30 years after Kholer and Milstein discovered how to make them. While I am thinking of it…how long have we been working on gene therapy??

Another issue surrounding stem cells that is often not discussed is cost…stem cell therapy will not be cheap by any stretch of the imagination. This is especially relevant considering that most governments have become very cost conscious when it comes to health and the US is on the verge of implementing cost controls on health care…(I won’t talk about the irony of the fact that the politicians who are pushing for stem cell research are the same ones that are behind the cost control legislation)…I expect that the price tag for a typical treatment could be anywhere from $50,000 to $500,000, and with this large price how could we afford to treat conditions such as Parkinsons or Alzheimers which afflict such a large number of people.

Hats off to Paul Knochel

Long before Phil Baran (a brilliant chemist indeed) was promoting protecting-groupless synthesis Paul Knochel and other were challenging people’s assumptions regarding the need for protecting groups in Grignard and Zinc-metallate mediated reactions.  A nice little paper in SynLett shows how to generate Grignard or Zincate of imidazole without the need for protecting groups. The trick here is the use of LiCl which aids the solubility of the reactants and reagents and increases their reactivity. Knochel doesn’t cite it but the current application of LiCl is reminiscent of Seebach’s work use of this salt to increase the solubility of cyclosporin in THF.

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Intermolecular ene reaction

March 29, 2007

This a little overdue…Some interesting chemistry reported in Journal of the American Chemical Society….Interesting not for the products that it produces but for the proposed mechanism, an intermolecular ene-reaction. From a retrosynthetic point of view one can imagine that the product of thisreaction could also be formed just as easily from the corresponding aldehyde via and Aldol reaction instead. However, the authors provide evidence to show that the reactants, as their enols, go through an ene-type process.

Given that this reaction occurs at room temperature simply by mixing the two substrates together is also noteworthy and makes me wonder why nobody had reported this before.

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