Monthly Archives: June 2009

National Organic Symposium. Tuesday Morning.

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Bad day for Th’ Gaussling to be away. The hounds are snapping at my heels at work.

I managed only to see Eric Jacobsen‘s talk on catalytic urea chemistry. Jacobsen’s system is pretty much a chiral proton ligand that can carry along a nucleophilic counter anion. Configured differently, urea’s and thiourea’s with BARF groups on the nitrogen can coordinate with chloride. This can lead to the abstraction of chloride to give a carbenium ion that can then participate in a enantioselective Pictet-Spengler type reaction. 

Jacobsen’s system resembles a radically stripped down enzyme in terms of 3-point binding interactions by hydrogen bonding.  Where Jacobsen went askew is the use of calculations to justify his mechanistic model. The models did not include solvent interactions when affording only 0-2 kcal/mol (!!) differences in energy. Naturally this did not set well with certain distinguished members of the Audience.  The ΔΔG’s did not correlate with the ee’s at all either.

A certain J.D. Roberts took great exception to Jacobsen’s molecular modeling results, resulting in the spectacle of a Harvard Professor frantically qualifying his slides and words as he back pedalled for all he was worth. There was some actual contrition there on the stage. It was quite a thing to see. There but for the grace of God go I.

National Organic Symposium. Monday Morning.

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The speakers for the morning of June 8th were Bob Grubbs and Magid Abou-Gharbia. As usual, Bobby Grubbs’ talk was concerned with the latest wonders of olefin metathesis. We saw ATM’s of molecular Cheerios. Pretty cool, actually. Grubbs got the trip to Stockholm for a reason and the work of his group continues to produce molecular wonders.  He was able to demonstrate the production of rings with degrees of polymerization in excess of 5000.  Using NMR and a carefully chosen ring monomer, they could sort out linear polymers from cyclic polymers. Linear polymers will thread a crown ether while the cyclic form will not. By attaching a crown ether (24-crown-8 ??) to polystyrene beads, they could collect and physically separate the linear from the cyclic forms. They were also producing brush polymers.

Prof. Magid Abou-Gharbia, Temple University, gave a talk with lots of fascinating insights into some current thinking on industrial drug discovery. At least from the point of view of a former Wyeth guy. I have been away from the pharma-related work for a number of years now and haven’t really missed it. But his talk has revived enthusiasms in me that have been in a long slumber. 

Anyway, he described the development of the anti-depressant Effexor and their efforts to keep the molecule simple and free of excessive stereocenters. Studies of the metabolism of Effexor lead to the discovery of the des-methyl analog, now called Pristiq.

Concerning High Throughput Synthesis (HTS)-

“… you’re going to get a lot of decorated molecules, but they are not going to be biopharmaceutically useful.”

Abou-Gharbia lamented the languishing of natural products chemistry. He gave some examples of Rapamycin work, which according to his presentation, was originally isolated from a soil sample from Easter Island.  Much productive work apparently has been derived from the modification of this macrocycle. It’s all in the literature.

One of the main take-away lessons from Abou-Gharbia is that workers shouldn’t get too focused on SAR. His advice was that structure-property relationships need an early examination as well. Dual optimization. If the bioavailability is low, then the in vivo activity will not match the in vitro activity- an expensive and time consuming realization.

Hail, Domes, and Beets

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We were treated to two hail storms today. The last one was unusually generous in the size and volume of hailstones that issued from the sky upon us. The jeep picked up a few dimples on the hood. Several tornados were spotted in the Denver metro area- It provided some real excitement for the emergency people besides the usual fare of grisly car wrecks and domestic abuse calls.

A low level easterly upslope flow injected humid, unstable air into westerly higher level flows. The result? A large scale shear zone with lots of convection potential. Vigorous convection and lots of moisture energizes hailstone growth.

Hail Gaussling!

Hail Gaussling!

Work is progressing on the new dome at the LTO. The observatory is adding a second dome for a very special 24 inch reflector- The Cole Telescope. Another fellow and I from LTO took posession of this telescope at the Mt. Wilson Observatory several years ago with the understanding that we will provide continued public access.

Funding for the operation of the telescope at Mt Wilson had dried up and the scope was taken out of service. We will be attaching a camera at the Newtonian focus for remote and internet use rather than for eyeball action. The instrument also has a Cassagrainian focus. This telescope was used in the 1960’s during the Apollo project for IR study of possible landing sites on the moon. The primary does have a ding in it due to a gravity accident. Supposedly, a grad student or post doc dropped an object on the 24 ” primary and chipped it. Today, the chip is painted black and it produces only gasps of horror by visitors.

An addition to the observatory building was completed a year ago. The steel pier that will support the telescope has been fabricated and painted. A new drive mechanism and software is in the works and is supported in part by a donation by Software Bisque. Once the scope and mount is bolted onto the pier, the dome will be lifted into place. A solar trickle charger/car battery power supply will energize the electromechanical worlkings like the slit and windscreen.

New dome bristling with Cleco's awaits the riveting crew

New dome bristling with Cleco's awaits the riveting crew

Rivet crew skins the frame of the new dome

Rivet crew skins the frame of the new dome

On a different topic, the first production of Rick Padden’s Beets was a genuine success. We came up short 30 seats for an all time attendance record for a play at the Rialto in Loveland. The play was well recieved and we look forward to doing another production in the area.

Back Porch Set for "Beets"

Back Porch Set for "Beets"

Organic Symposium

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Despite my previous gritching about it and despite trying to stay below the radar at work, the boss has requested and required that I attend the Organic Symposium at CU Boulder. I’ll bop over there later today to register and walk the poster session. Maybe there will be some useful grist for the blogmill.

No better reminder of the scientific pecking order than to skuttle around in the shadows of the great grant writers of our time. A certain speaker with a Nobel Prize casts a shadow so large that it is reported to weigh nearly 5 kilograms. Fancy that!

Patent-isms

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Odd descriptions of matter and the peculiar turn of phrase abound in the chemical patent literature. Here are just a few of my favorites (italics mine)-

  • “… wherein the substituents have the following significations:”
  • ionic layered compositions  (translation- clay)
  • Donor solvents (translation- certainly an ether, perhaps an ester)
  • A non-coordinating dispersant (translation- a hydrocarbon solvent)

The deal with the devil that you make in getting a patent is this- in exchange for a 20 year monopoly, you must disclose to the public enough enabling information that a confused citizen could determine if he/she is infringing on the patent and reasonably avoid infringement. But this does not stop the use of opaque vocabulary and unusual juxtapositions because, after all, one skilled in the art should be able to decode the many obfuscations applied to their area of specialty. Shouldn’t they…? Or, perhaps the obtuse vocabulary is meant to daze and confuse the judge and jury. Hmmm.

Epiphany at Joe’s Crab Shack

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Whilst knoshing on broiled tilapia and shrimp at Joe’s Crab Shack last night, I innocently offered the question “Who recorded the song that is playing?” As I washed down my entree with ice water and neatly dabbed my napkin at the corner of my mouth, our friend’s teenage son (who was sitting quietly across the table from me) twiddled his wireless device and a minute later handed it over to me.

As I looked at the display it slowly dawned on me what I was viewing. The device had sampled the music and provided a list of song titles (with the artists) that matched the sample!  WTF!? 

Crimony! I need to get out more. I had no flippin’ clue that this capability was available for use outside the NSA!

There is a saying that any sufficiently advanced technology is indistinguishable with magic. That was the case for me last night.