Reaction of the Week #2 - Strecker reaction & amino acid synthesis

I selected the Strecker synthesis based on a recent Nature paper by Jacobsen and coworkers using an asymmetric Strecker synthesis to create unnatural α-amino acids. The classical Strecker reaction, first reported in 1850 (!), involves the reaction of a carbonyl acompound (ketone or aldehyde) with ammonia (to create the free amine) or primary or secondary amines to form an α-amino nitrile, which can be followed by acidification to hydrolize the nitrile group to a carboxylic acid.  (The intermediate may also be reduced to produce 1,2-diamines or undergo α-substitution chemistry following deprotonation at the α-position, provided there is an available proton). The mechanism/sequence concluding with acid-catalyzed, sans the formation of the iminium and acid stepwise, is shown below.

The entire sequence can be achieved in one pot.  This reaction and the synthesis of amino acids can be easily rendered asymmetric using a chiral Lewis acid or an organocatalyst (in the latter, the additive would coordinate to the imine nitrogen...it would obviously have to be trisubstituted/neutral for this to occur) and another basic moiety at the appropriate distance would associate with the proton from HCN, pulling H away and direct the CN to whichever side of the imine it is closest to.  Anionic CN sources are generally a problem because of the toxicity of the CN anion, and so improvements and modifications to the reaction are continuously made.  Examples of reagents include Bu₃SnCN, TMSCN (which is expensive and difficult to handle), Et₂AlCN, and HCN; while KCN and NaCN are desirable as they are inexpensive and easily handled cyanide salts, they are not typically seen presumably due to their low solubility in organic solvents unless buffered aqueous medium is used, according to the authors of the Nature paper.

A neat caveat to α-amino nitriles is that if they are treated with a heavy metal salt (such as a Ag(I) salt), a Brönsted or Lewis acid, cyanide can be a leaving group to reform iminium which is trappable by a nucleophile - when the nucleophile is organometallic, the reaction is the Bruylants reaction.

Jacobsen and coworkers have developed a chiral catalyst derived from (S)-tert-leucine (read: inexpensive and accessible) to achieve asymmetric imine hydrocyanation.  Using 2 equivalents of TMSCN, 2 equivalents of MeOH, and 0.5 mol% of the catalyst in 0.2 M toluene at -30C for 20 hours, excellent yields were achieved with good to excellent ee with the exception of only a few of the reported substrates which were still in good yield.

A nice graphic that explains the enantioselectivity was presented in the paper:

Another example which is included in the entry in Kürti and Czakó text is in the synthesis of (-)-α-kainic acid, a neurotoxic compound that induces seizures (it is used in research commonly to induce seizures in rats).  It is a kainate receptor agonist (hence its name), and since the kainate receptor is one of the "ionotropic glutamate receptors" it is understandably a stimulant (glutamate is an excitatory neurotransmitter).  The Strecker reaction in this case is mediated by zirconium with the Schwartz reagent to form imine, which was not isolated but directly treated with cyanotrimethylsilane to produce the α-amino nitrile.  Hydrolysis to the acid and concomitant epimerization selectively led to (-)-α-kainic acid.

I hope you like the festive-colored kainic acid!

Starfruit visualied with SEM

Have you ever had starfruit (also called carambola)?  Personally, to me they taste like apple, without the grainy texture, and they're super cute.

The Talapin group at the University of Chicago has taken some SEM images that look JUST like them.  Yum!

Size-Dependent Multiple Twinning in Nanocrystal Superlattices 
J. Am. Chem. Soc., Article ASAP (doi: 10.1021/ja9074425)

 

Reaction of the Week #1 - Schmidt reaction

I intended this to come out at least a week ago, but with the holiday season seems to come family crises and deaths.

So. The Schmidt reaction.  Its seminal publication came in 1923 It's pretty commonly known, and very similar to the Curtius and the Hofmann rearrangements taught in undergraduate organic II.  It can transform a carboxylic acid into an amine one carbon shorter, an aldehyde into a nitrile (generally aromatic aldehydes), or a ketone into an amide or lactam (depending on the starting material) with the addition of HN₃, hydrazoic acid, in acidic conditions (the first few times I looked at it my brain saw NH₃, so watch out).  Other groups that may react with HN₃ are nitriles, imines, diimides, some alkenes, and alcohols, according to the Kürti and Czakó text, as well as any other acid-sensitive groups.

The intramolecular version appears in the literature frequently.  An alternative electrophile to those listed above (and the acid-to-carboxonium shown in the mechanism) is a leaving group, such as an iodide, triflate, tosylate or nosylate.  A recent JACS Communication by Kapat and coworkers at the University of Berne (Switzerland) used an acid-free version of this variation that produced great enantioselectivity of a natural product from tree frog skin, (-)-indolizidine 167B.  (This target is fairly attractive for the challenge of that particular stereocenter; a quick Google search will show you quite a few other approaches.) This is the TOC graphical abstract...to be honest the colors are what made me check it out.

The full synthesis is detailed below. There was a few interesting reactions so I wrote the synthesis out stepwise.  Copper-catalyzed asymmetric allylic substitution with a Grignard reagent enantioselectively installed a t-butoxypropyl group.  The terminal alkene then underwent carboazidation - which is a really neat reaction, though at first glance the reagents looked like some gen. chem. magic.  Reduction of the ester to the alcohol which was tosylated and then reduced resulted in the desired propyl side chain.  The t-butyl ether was cleaved under mild Lewis acidic conditions to produce the free primary alcohol.   Note the box with various deprotection conditions for t-butyl ethers (the group is generally installed with isobutene in the presence of acid).

The last few steps where the Schmidt comes in are as follows:

The free alcohol is converted to the triflate, which is nucleophilically attacked by the azide anion.  A 1,2-alkyl shift ejects nitrogen gas, and reduction of the iminium product results in 98% ee, 79% yield of the natural product. 

Rant #1 - Ph.D. in immunology required.

This post has been hidden because certain readers couldn't handle my tone.

"Named reaction of the week" will start tomorrow - if you have any requests or feel a certain reaction warrants covering, do let me know!

-->

Pauciflorol F - Larock annulation & misassigned spectra(?)

If you’re familiar with the current organic chemical literature, I’m sure you’re aware of the huge influx of research about resveratrol and polyphenol natural products and their antioxidant properties in the past few years.  Not only are polyphenols being studied for their potent antioxidant capability, but also their anti-cancer and anti- other things as well.  

With that said, I’ll admit that I haven’t been super psyched about the chemistry to make the little guys, since all the molecules are so similar and a lot of the chemistry is radical-based, until I saw one recently in Org. Lett. (doi: 10.1021/ol902141z) that featured a Larock annulation to form the 5-membered ring of an indenone, the double bond of which was subsequently reduced to produce pauciflorol F.  Two total syntheses of this polyphenol have been reported (She, Pan, et. al. [Chin. J. Org. Chem. 2006, 26, 1300] and Snyder [doi: 10.1021/ja806183r]).  This paper differs in that the authors use a palladium-mediated cyclization approach to the indenone.

The chemistry developed by Richard Larock found its way into my heart as an undergraduate; I was already enamored with transition metals, but watching palladium bounce around in these reactions really just wow’ed me.  You can check out the group’s webpage for an idea of the substrate scope of this chemistry.  Kurti and Czako included the Larock Indole Synthesis in their named reaction text, the mechanism of which is detailed below:

Alternatively, bromoarenes have been used as well as applied to other target motifs.  This paper uses o-bromobenzaldehyde substrates and cyclizes with a di-arylated alkyne with polymethylether substituents, which in the last step are globally deprotected to produce the polyphenol. 

They naturally obtained both regioisomers as there is not much steric difference between the substituents, but both were useful because they could be used to form different natural products.  The rest of the first sequence attempted follows: 

What made me squint my eyes at the details was the structural revision of a key intermediate, one step prior to the final pauciflorol F, compared to the previously reported structure - the last one just shown.   According to Snyder, the enolization attempted in hopes of epimerization of C2 of the compound shown with KHMDS and water quench provided the trans-product; however, the authors of this paper found that enolization with substoichiometric K₂CO₃ in 3:1 MeOH:MeCN in an effort to epimerize C2 resulted in the formation of the a-hydroxyindanone instead (but reducing the double bond in the presence of KOH induces epimerization in-situ so they can get around this inadvertent oxidation).  The ¹H NMR data, shown below, displays two singlets, one broad, shifts of which agree well with the revised structure – compare these two the peaks as reported in the current paper and decide for yourself whether this was an accidental interpretation of the spectrum, seeing as how in the original paper, the mass coincides with the desired product and not the actual product…. who is correct?  (2a is the Pan paper, 2b is the Snyder paper, and 6 is the current paper - click on the image to see the full thing.)  

The top 2 spectra are published for the product that Snyder reported; the second is Snyder's spectrum for that compound, supposedly, while the 4th is the current author's spectrum for the reassigned structure.  The last is the starting material.  

Personally, my organic 1 students would not accept that the two singlets describe the trans-product.  How can two papers report strikingly similar ¹H NMR spectra, but completely different masses as the result of the same reaction?  Fishy.  Sure, the conditions were different.   Fortunately for Snyder, the global deprotection with BBr₃ that followed resulted in a reductive removal of the inadvertently installed OH group and did, in fact, furnish pauciflorol F.  The current paper confirmed that this was indeed possible, and poked around the mechanism a little bit. Was the original structure misassigned purposefully because there was no way to explain it and the fact that the natural product was still formed made sense?  Or are the different reaction conditions enough to cause two different pathways/structures to form?  Oxidation happens in one case but not the other?  Was it just ignorance? Who knows… if there's something I'm missing, please let me know! 

Lengthening the C-O bond

Ok, ok, not actually lengthening the bond, but just in the graphic.

Anhydrous Hydration of Nitriles to Amides using Aldoximes as the Water Source
JOC ASAPs (doi: 10.1021/ol902309z)

 

A real post coming tonight! It required a lot of consideration.  You'll see why.

There are telephones inside C60!!

Another fun TOC graphic so soon?  Is it possible to devote a blog to this?  I may have to reconsider my work here.

This time, it's from an Acc. Chem. Res. ASAP, a dream come true... With the way this week is going lab-due-date-group-meeting-jump-off-roof-wise, I'm grateful!  I think the little guy should have a cigarette hanging out of his mouth, though.

The Spin Chemistry and Magnetic Resonance of H₂@C₆₀. From the Pauli Principle to Trapping a Long Lived Nuclear Excited Spin State inside a Buckyball  (doi: 10.1021/ar900223d)

If you could hold that red phone up to the world, what would you tell it?

Antipsychotic Asenapine

In August of this year, the drug asenapine (sold as Saphris by Shering-Plough) was approved by the FDA for treatment of schizophrenia and manic episodes of biopolar I disorder, according to a recent news article in Nature Reviews Drug Discovery (doi:10.1038/nrd3027).  Asenapine is an atypical antispychotic. The tricyclic 6-7-6 ring structure is common to most of the the atypical antispychotics (including clozapine and olanzapine, but not risperidone).  What makes them atypical is that they not only treat the "positive" symptoms of schizophrenia (hallucinations, delusions, mania) but the "negative" ones as well (depression, cognitive impairment). 

A SciFinder search revealed 3 patents with published syntheses of the drug; surprisingly, no papers so far with SAR studies or anything of the sort, and just enough clinical trials to allow the drug to be marketed.  The drug wasted no time getting to the market - at least, according to the literature I looked through - which for a mental disorder like schizophrenia for which there is no truly good treatment, only adequate treatment, is wonderful.

Two patents had two different approaches (and the others were either duplicates or elaborations), and the most recent was an elaboration on one of the others.  The first, from 2006, sought to make the trans-pyrrolidine as efficiently as possible to improve upon the former synthesis.  The synthesis on a whole, though, is extremely steppy.  The second, in 2008 (Int. Pat. #: WO 2008/003460) instead chopped the molecule in two via a cyclization between a stilbene and an in-situ generated azomethine, followed by an Ullman condensation to connect the phenol with the other ring; use of the trans-stilbene naturally leads to the trans-ring juncture.

To make the stilbene, HWE:

 

You can obviously see where there's room for synthesizing analogues here by using a different benzyl bromide in the first step.   The coupling partner used in the next step is activated in-situ by CsF or TFA.  I think it looks like a handy synthesis.

I love figurative TOC graphics!

If I find a TOC graphic that's funny, it's going here.

Come on... this is awesome: 

From EJOC,  "Configurational Isomers of a Stilbene-Linked Bis(porphyrin) Tweezer: Synthesis and Fullerene-Binding Studies." (doi: 10.1002/ejoc.200901002)

 

From the same journal... don't you think they look like those pasta wheels we used to make art with in kindergarden with glue and tempera paint?

"Highly Efficient Fluorine-Promoted Intramolecular Condensation of Benzo[c]phenanthrene: A New Prospective on Direct Fullerene Synthesis" (doi: 10.1002/ejoc.200900976) 

Piperazimycin A: A Cyctotoxic Cyclic Hexadepsipetide

Li, Gan, and Ma's recent natural product synthesis of piperazimycin A, the structure of which was reported in 2007, in Angewante Chemie (doi: 10.1002/anie.200904603), attracted me admittedly because of how gorgeous the 18-membered ring with 6 carbonyls pointed toward each other is - seriously, look at it!  Stare into the center of the ring - the oxygens are sort of mesmerizing in a hypnotic sort of way, no?

Amino acid chemistry is not my favorite; it's kind of... blah.  Feels archaic somehow. But these amino acids are pretty funky - each fragment was formed with pretty standard chemistry (protections/deprotections and all).  The N-N bonds were introduced with benzyl carbazate and t-butyl carbazate.  The cyclization to form the leftmost-indicated piperazic ring occurred via Mitsunobu condition-induced Fmoc deprotection of the amine (which appears to be novel according to the article) followed by substitution of an alcohol, while the left occurred via Boc deprotection-induced displacement of a triflate and the top via Troc-deprotection induced displacement of a triflate.  Don't forget the structures of these (the deprotection conditions used in the paper alongside):

The most interesting part is the macrocyclization; rather than doing a macrolactonization between an acid or ester and an alcohol, the authors used a substitutive strategy by a carboxylate anion attacking a chlorine-turned-iodide leaving group to produce Piperazimycin A in 3.6% overall yield in 26 linear steps.  Tight.  Note the hexachloroacetone (HCA) used for chlorination in the Appel reaction instead of CCl_4. Equally toxic reagent, but way cooler. 

Japp-Klingemann reaction and lots of anti-s

A 'just accepted' article in Bioorganic and Medicinal Chemistry (doi:10.1016/j.bmc.2009.10.012) caught my attention because of the number of "anti" activities stated in the title for a particlar 'new' class of compounds, 2-arylazobenzosuberones: "Synthesis, Tautomerism, Antimicrobial, Anti-HCV, Anti-SSPE, Antioxidant and Antitumor activities of Arylazobenzosuberones."  From one common precursor, 12 compounds were synthesized with variation of the arene group of the diazonium salt coupling power.  Reaction of 1-benzosuberone-2-dimethylaminomethylene with aryl diazonium chloride resulted in the Japp-Klingemann type cleavage of the dimethylaminomethylene group.

The Japp-Klingemann reaction normally involves the reaction of beta-keto esters or acids with aryldiazonium salts in the presence of base to form hydrazones, usually in aqueous medium but in alcohols if solubility is poor:

In this paper, however, an alpha-dimethylaminomethylene group functions as the original ketone in this case, so there's no need for a strong base - the conditions for the reaction are sodium acetate in ethanol at 0-5 °C for 20 minutes, then overnight in a refrigerator to crash out the product.

So for all the anti's - 8 of these compounds were tested for inhibitation of growth of 4 strains of bacteria and 4 strains of fungi using the agar diffusion method.  Referenced antibacterial drugs are mentioned, but not identified nor is comparison data for the standard included in the data presented in the form of Minimum Inhibitory Concentration (MIC) values.  The paper claimed much better activity of some of the compounds than the standards, but the units of the values are GRAMS per mL. That's HUGE to me... the lowest measured was 0.313 g/mL.  The tetra- and pentacyclic compounds below weren't tested, but I would've liked to see them tested, since the heteroarene rings are such great pharmacaphores and they're much different than the rest of the bicyclic azoketosuberones.

Antioxidant activity was assessed with the DPPH radical scavanging test, a colorimetric assay that determines XXX, with ascorbic acid (vitamin C) as a standard.  The second test was inhibition of ONOO^- (ooohhhhnooooooooooooooooooo!) which can cause tissue damage from oxidation and nitration of lipids, proteins DNA and carbohydrates.  These results were in IC₅₀ values, thank goodness, but like all the other biological activity tests, the hydrazones were just as good if only slightly better than the standards, if standard data was even shown.  They aren't orders of magnitude different.  What did I expect?

When I read these kinds of med chem type papers I take an especially harsh eye to it, definitely not because I'm a scientist and thus am cynical (which I definitely am), but because it's a habit from being a reviewer for a school journal.  Everything we got in seemed to me so unimpressive that I finally got fed up and quit being on the board.  The biological studies in this paper made me feel like that.  Please, please don't talk up your results.  Just tell them how they are and let the community decide whether or not your compounds are the shit.  When I just now got around to opening the Kürti and Czakó text, I wasn't surprised to see a similar ring system used to make a remarkably similar product by G. Primofiore and co-workers in 1993 (see below, from p.225)... ripoffs! Can't believe I wasted that time. The only thing I liked was that all the compounds were in the yellow/orange range in moderate to good yields... slightly redeeming.

Look familiar? 

One reaction at a time

Amen...
http://www.coronene.com/blog/?p=1017

Cancer doesn't like sugar chemistry

I shuddered when I saw the sugary graphical abstract for Danishefsky's recent JOC Note, "A Practical Total Synthesis of Globo-H for Use in Anticancer Vaccines."  (doi: 10.1021/jo901682p) And then a moment later, I realized... anticancer vaccines?!  Where the hell have I been?  Apparently, this glycosphingolipid compound Globo-H is an antigen that was isolated in 1983 from a breast cancer cell line, and is now known to also be over-expressed on the surface of other types of cancer cells (prostate, ovary, lung, colon, and small cell lung cancers).  Administration with alpha-galactosylceramide induces antibodies against globo-H and SSEA3 (the pentasaccharide precursor of globo-H).  If I understand correctly, it's the equivalent of administering a dead or partial or similar virus in order to trigger the formation of antibodies.  The pentavalent vaccine also contains other antigens that are overexpressed on cancer cells (prostate and breast).  A search for "globo-h" on pubs.acs.org alone produces 118 hits, encompassing syntheses, development, and animal studies. 

There have been other syntheses, including that of Schmidt, Boons, Wong, Seeberger (2002 and 2007), and Huang referenced in Danishefsky's paper, and an earlier synthesis of his as well which was too low-yielding.  The ABC trisaccharide that will be incorporated later was synthesized according to the previously reported Cp₂Zr(OTf)₂-mediated coupling.  The starting material was synthesized via α-epoxidation followed by glycosylation to produce the DE disaccharide shown below; coupling of this molecule with the thiofucosyl donor (with fucose being a hexose deoxy sugar) selectively produced the α-trisaccharide. The conditions screened that produced the highest yield, 80%, were Cp₂Zr(OTf)₂ with 5:1 toluene:THF and 2,6-di-t-butylpyridine(hindered base) in the dark over 72 hours, but the conditions the authors moved forward with produced an impressive 78% yield in only 4 hours:

That's not so scary - silver triflate draws the chlorine away from TolSCl, which pulls ^-STol in after the alcohol displaces it. The next step involved a (to me) funky iodine reagent, I(coll)₂ClO₄ to promote iodosulfonimidation of the now DEF glycol.  The sulfonamide blocks any attack from the bottom face of the ring, forcing the nucleophile in the next step to attack from the top to form the β-isomer. Treatment of the crude intermediate with lithium ethanethiolate leads to the complete DEF donor in 75%, ready for coupling with the ABC acceptor.

The last coupling proceeds without fuss in 72% yield after treatment with methyl triflate. Deprotection of TIPS with TBAF and Bn with sodium reducing conditions followed by global peracetylation leads to the target hexasaccharide:

 

The last steps to append this molecule to the carrier protein KLH (keyhole limpet hemocyanin) were previously published by Danishefsky and co-workers, as was to covalently link the molecule to an amide (doi: 10.3987/COM-08-S(D)82). I'll add those as soon as Heterocycles loads on my work laptop tomorrow. 

Uranium = C-H Activation

Uranium is the 92nd element, and the last naturally occurring element, in the periodic table.  I've always held an intense disdain for it since my final project in junior Inorganic Chemistry was to elucidate the energy levels and their symmetry of UO₂. F AND d orbitals?  Seriously?  No one else had to deal with f orbitals. I know it was a test because I was a straight A student and he wanted to see if I was as brilliant as I seemed... nope.  It was an awful presentation, and a classmate was nice enough to bring me home on her red, brand new Vespa to cheer me up. (Bitch.)  Anyway, what I didn't know at the time was that organouranium compounds, and organoactinides on the whole, are actually freaking awesome.  Uranium complexes can catalyze oligomerization, dimerization, hydrosilation and hydroamination of terminal alkynes, hydrogenation of arenes, polymerization of olefins, and coupling of isonitriles with terminal alkynes, all extensively reviewed in Coordination Chemistry Reviews in 2006 (doi:10.1016/j.ccr.2005.12.007).  It's a really interesting review, even if you just check out the schemes.  Another published last year on organouranium and organothorium specifically is also worth checking out (doi 10.1039/b614969n).

What caught my eye was a paper that just came out in Early View in ACIE by the Diaconescu group at UCLA, in which examined the reaction of a dibenzyl uranium complex with multiple equivalents of methylimidazole.  They found that instead of merely coordinating, as one would expect such a heterocycle to do with a transition metal, the metal center inserted itself into the C2 position's C-H bond on two separate methylimidazole molecules; a third equivalent coordinates via the lone pair.  By using deuterated benzene as the solvent, they were able to observe that two equivalents of toluene are also formed, confirming the C-H insertion steps. Mechanistically, uranium doesn't proceed through oxidative addition or reductive elimination steps like the transition metals; rather, it goes through a sigma-bond metathesis type 4-center transition state. The C-H insertion positions are highlighted in red.

That's not all - after the imidazoles are bonded to uranium, crazy sh#t happens.  Two of the imidazoles couple, which prepares one for ring-opening, then migratory insertion to create a crazy structure that  I wouldn't believe if they weren't supported by crystal structures. It's not surprising that it requires a lot of heat and a lot of time to accomplish.

 The intermediates in brackets were not able to be isolated in this case, but when 1-methylbenzimidazole was used instead of 1-methylimidazole, the reaction stopped at the first intermediate directly after the imidazole coupling, and they were able to isolate and confirm the structure of the complex.  Here are the crystal structures of the reaction with 1-methylimidazole to compare with the products (with 50% and 35% ellipsoids, respectively).

Achmatowicz reaction

Everyone loves neat tricks in synthesis that are not as easy to spot in retrosynthesis as oxidations or reductions; one of these I came across recently is the conversion of furans to tetrahydropyrans, the Achmatowicz reaction, the seminal publication of which was in 1971 in Tetrahedron:

This reaction was used in a few total syntheses; besides those mentioned in the Wikipedia article, I particularly like O'Doherty's synthesis of the indolizidine (-)-D-Swainsonine published in Org. Lett. The four carbons that will form the five-membered ring of the bicyclic system was formed using the Achmatowicz reaction. 2-Lithiofuran opened the gamma-butyrolactone to install the alpha-oxygen; a TBS protection allowed for asymmetric Noyori reduction of the ketone, installing the necessary stereocenter for the substituent on the tetrahydropuran for the subsequent steps. The Achmatowicz was achieved using NBS.

Other than modifications to the ring's functional groups, the carbonyl was converted to an azide in several steps which was used in the second to last, pivotal step of the synthesis, closing the 5-membered ring via reductive cyclization to complete the indazolidine ring system. (The benzyl group is hydrogenated off, allowing the isomerization to the aldehyde which is then attacked by the nitrogen and the oxygen eliminated.) That makes for two rearrangement-type reactions to form the final product - I won't get into overall strategy and the greater story of the synthesis of the molecule and its enantiomer, but I just wanted to point out how the Achmatowicz was used creatively to make a pretty neat molecule.

2 - Crop circles

Today, the topic of the show “Is it real?” was crop circles – and I don’t know anything about crop circles, so I watched. They truly are beautiful.  It seemed that believers somehow managed to use the evidence that they are man-made to their advantage, and find meaning in it.  They seem like perfectly normal people with normal lives, except for the fact that their brains interpret the actions of man to be the actions of aliens trying to communicate, and that they can meditate crop circles into being.  Me, personally, I don’t care about crop circles.  I find that they are incredibly annoying, as anything in the press that gets so much attention is, but they are also occurring at great expense to farmers who are having a hard enough time already these last couple decades.  I just can’t imagine what it is in one’s brain that makes them prone to this kind of ideology – there must be something genetic going on there to make their beliefs so malleable.  I’m going to see what kind of research has been done about this.  In the meantime, I have acquired lots of gorgeous pictures of perfectly symmetrical crop circles for desktop backgrounds! And you can hire your very own crop circle makers, didn't you know?  

I need to learn.

As all graduate students know all too well, you not only attain a Ph.D. by becoming an expert in your sliver of the scientific universe, but by being obviously well-read in the literature of your general field as well. As an organic chemist, I am currently working on a project that does not allow much diversity in the way of synthesis, but I fully intend to leave this place with a more comprehensive and intuitive ability to predict reaction outcomes, more named reactions under my belt, and understanding of combinatorial and solid-phase synthetic techniques. None of that can I really pay much attention to during the work day, so in my *copious* free time, I will learn them here, and if you care to, you can learn too. I also dig science news, not only because sometimes it's really cool shit, but also because it helps me hang on by that little string by reminding me of the greater picture, so I'd like to learn more about "science" as well. This blog is my ticket to NOT remaining a one-trick pony.