The Realm of Organic Synthesis

Why haven’t you come to the new blog hosting?  I’ve hyperlinked it for you:

http://therealmoforganicsynthesis.blogspot.com

There.  Now you have no excuse.

Hope to see you there!

-J

I recently had a revelation about the targets I’m trying to synthesize.  While I’m surprised no one (in our group) ever picked up on the possibility, it occurred to me that the compounds I’m preparing could cyclize given the surrounding functionality.  As such, I went crawling through my old physical organic notes and started rereading the section on Baldwin’s rules.  However, this concept is not to be confused with the Baldwin Hypothesis—formulated by a couple of theatre geeks at Assumption (myself included)—which states that the incorporation of any Baldwin brother into a movie or television series (other than Alec) will devalue the overall premise or plot ten-fold (case in point, the X-Files).

Rather (to the uninitiated), Baldwin’s rules/suggestions are guidelines governing the tendency for substrates to cyclize based off of thermodynamic and electronic considerations.  In other words, there are certain conditions (functional groups, orbital geometry, electron flow) that will cause a substrate to cyclize if given the opportunity—sufficient reactivity.  In the mid to late 70’s, Jack Baldwin and co-workers published observations from intramolecular conjugate additions of oxygen nucleophiles resulting in cyclizations (J. Org. Chem.1977, 42, 3846-3852).  Ultimately they concluded the following:

 

“There are substantial differences in the ease of nucleophilic ring closures, strongly dependent on ring size, geometry of reacting terminus, and the endo or exo nature of the reactions.”

 

March’s Advanced Organic Chemistry 6th edition (specifically p. 306) does a good job outlining the basic guidelines of such a phenomenon.  The suggestions for cyclization are spelled out for sp (digonal), sp2 (trigonal) and sp3 (tetrahedral) hybrids based on the flow of electrons—in the ring (endo) or outside the ring (exo).  Specifically (for you underpaid, overworked grad students):

 

Tetrahedral systems: 3—7-exo-tet cyclizations are favored whereas 5—6-endo-tet are not.

Trigonal systems: 3—7-exo and 6—7-endo-trig are favored whereas 3—5-endo-trig are not.

Digonal systems: 5—7-exo and 3—7-endo-dig are favored whereas 3—4-exo-dig are not.

 

Of course, with any physical organic concept, there are exceptions to this rule (see: J. Am. Chem. Soc. 1985, 107, 1778-1781; Tetrahedron Letters 1985, 26, 4455-4458; Science1993, 259, 490-493; Chemical Communications 2007, 2698-2700).  The common thread in the entirety of Baldwin’s suggestions is proper alignment of the orbitals (geometrically) in the transition state.  If the orbitals cannot align, the system has less of a chance to undergo cyclization (Alder had a fantastic set of notes that adequately bridges the gap between electronics and synthesis; Baldwin’s rules are ~1/2 down the page).

As in many cases, the challenge lies not in utility but, rather, in control.  Often, this implies altering functional groups (sorry Phil Barran) or limiting your synthetic route or (my personal favorite) coming up with a brand-new, creative way to skin the proverbial cat.  My next endeavor: a search for a Mitsunobu inversion-type reaction that generates less waste than the common method.  Any suggestions?

P.S. This server (though free) is beginning to annoy me.  Font colors are spontaneously changing, images are difficult to upload (I had a great graphic to insert into this post), and it tends to crash at odd hours (it screwed up Safari–my browser to all you PC people–last night).  As such, I might be switching in the near future.  I apologize for any inconveniences.  Go Sox.

Across my department, more and more people are listening to mp3 players.  My quasi-cynical side seems to think it’s to subconsciously drown out the noise of perpetual University bureaucracy that hinders the creative processes.  A recent postdoc from Germany lashed out at colleague of mine over maintaining focus and composure in the lab; this person was listening to their headphones while running a flash column.  True, many accidents are due to distractions (e.g. talking on the phone while driving, listening to an mp3 player while working in the lab, gossiping when you should be paying attention—a recent infuriating pet peeve of mine). 

I try to stress the importance of concentration in my undergraduate labs.  Specifically, my syllabus/course objectives state that personal items (i.e. cell phones, mp3 players, food) are unwelcome in my lab for safety reasons.  I don’t want my kids accidentally getting sprayed with 6 M H2SO4 by their hoodmate who’s stuck in a rare live track from Dave Matthews Band.  Of course, many of my colleagues both at UA and across the country feel the same way: University of Colorado, California Polytechnic State University and even St. Olaf College in Minnesota. 

In a brief literature search, I’ve found little information about modern laboratory safety (specifically covering distractions).  Is the banning of headphones (or even music) in the lab a common sense issue?  Is it something we just take for granted?  What if there’s substantial downtime (you’re caught up, but waiting for something to finish refluxing)?

Fundamentally, the postdoc’s comment makes sense.  However, (and I’ll speak for myself) my yields are usually better (by >15% in some cases) when I’m in my own world of music and chemistry—two seemingly unrelated things that connect at a higher level.  Synthetic chemistry really is an art (I’ve sat through several total synthesis seminars that overly emphasize this notion), and I know many artists who rely on music as their motivation and inspiration.  So, if your lab bench is (somewhat) tidy, you’ve eliminated clutter around your work area and are habitually safe, why not plug in?

True, most of what inspires me would probably piss my labmates off if commonly audible (Sevendust, Disturbed, POD, etc.).  For the time being, I guess I’ll resort to my little 1 GB mp3 player to get me though a flash column or reagent preparation or TLC work.  However, I will often be in silence when I write in my notebook or when I’m reading a paper—stuff that typically requires thinking.  A lot of times, I’ll just listen to old Opie and Anthony clips (particularly the ones that feature Andrew Dice Clay), just because it makes work a little more bearable.  Do you listen to an mp3 player at work?  What’s on your playlist? 

Changing gears for a second, how about those Red Sox?  Definitely a nail biter late in the game last night (I almost lost it when Okey gave up the two-run shot to Atkins in the bottom of the 8th).  Truthfully though, part of me is glad for the World Series to be over because the commentary by the Fox network has been awful at best.  My wife and I have been making fun of the “cancer music” they play going into and coming out of commercial for the better part of a week.  Plus, everyone seems to find Joe Buck and Tim McCarver annoying on a good day.

On a side note, it’s been reported that Alex Rodriguez is opting out of his contract with the Yankees.  Does this mean the Red Sox’ll pursue A-Rod by dropping Ramirez?  It’s going to be an interesting offseason. 

 

P.S. Here’s a couple choice selections from my playlist:

From Chaos – 311; Rain Song – Cold; Don’t Tread on Me – Metallica; Metalingus – Altar Bridge; Face to Face – Sevendust; Ugly - Sevendust; Just Stop – Disturbed; Wildfire – P.O.D.; Stillborn – Black Label Society; Valentine’s Day – Linkin Park; Chasing After - Tantric; Won’t Back Down – Fuel (*my ringtone); Shinedown – Godsmack; Given to Fly – Pearl Jam; Crop Duster – Pearl Jam; On the Sea (Recorded at the 9:30 Club in DC, c. 2005) – Vertical Horizon 

Truth be told, I have 3 blog entries sitting on my desktop, but so much has gone on in the past month or two, it’s been tough to keep up to date.  Thank you to whomever just posted a comment (KRP) the other day in response to my Facile Iodination rant from a few months back.  Ironically, I was just discussing this concept the other day with a friend of mine who’s currently searching for an ORP idea; I recommended devising a method using a low-valent heteroatom that would wash out on workup (specifically, sulfur).  At any rate, my recent commentator has provided me with a reference that bears mentioning (Bull. Korean Chem. Soc. 2004, 25, 1143-1146).  The article features excellent yields in impressive times using cerium(III), microwave irradiation and sodium iodide as the halide source.  As someone who’s investigated green chemistry as a hobby (and also during my ORP), I’ll note that microwave chemistry still has a long way to go, but recent developments make the technology promising.  Since our group microwave is currently situated in the office side of the lab, and should probably be labeled as a biohazard given its current state, I’ll probably just stick to I2 and PPh3.

Our paper was submitted almost 2 weeks ago, and we’re hoping for a response from the editor by next week.  In actuality, the paper, itself, was finished 4 weeks ago, but we had significant problems with the template formatting.  As such, I became an instant expert using the style settings in Word.  I’ve also become addicted to using the editing characters.  At any rate, I’ll keep you up to speed with the (hopeful) success of the paper. 

I hope everyone is alright out there in internet/blog-land.  It’s been a really busy, stressful, irritating past month, but we’re making significant progress with the hope of a first paper in a month or two.  I’m in the midst of a linear synthesis marathon–busting my butt to make a compound for a last experiment or two.  

INTRO

Below are some thoughts about the Boston ACS conference recently held.  All in all, the meeting was okay—nothing seemingly groundbreaking.  The following updates were written in real time then edited at an Irish pub at 5-Points in Atlanta a day or two later (excuse the grammar in some places as I’ve recently become addicted to Shandys—Harp and Sprite). 

UPDATE

It’s 8:00 am EST, 7:00 am back home and I’ve been up since the crack of dawn after getting ~5 h of sleep last night.  I’ll mention that it is frigid in Boston (for the month of August) relative to the 3 consecutive weeks of 100+ degree temps in the south.  It’s taken me about an hour to learn how to efficiently navigate the conference program, and with that under my belt, I’ve just finished planning out my schedule at a Starbuck’s in Downtown Crossing earlier this morning.  Interestingly enough, I’m not the only one who finds the program somewhat confusing to navigate; the two gentlemen whom I met yesterday had similar problems.  As I figure out the schedule, an event coordinator is informing the room that there are errors with respect to the scheduling info in the program.  I guess bumps in the road are fairly common for conferences.

So, what’s on the agenda today?  Some interesting methodology this afternoon, possibly a session on negotiation techniques, and a definite trip to the expo.  Though, strictly as a synthetic guy, I’m interested in seeing some of the “big dogs”—Boger, Wipf, Baran, Smith—present their recent works on peptide-based natural products.  On a much more nerdlier level (I realize it’s not a word) it’s analogous to a little kid getting to watch Curt Schilling pitch in Fenway.  Sadly, some of the guys I was hoping to see speak aren’t scheduled, though. 

Plus, I’ve been invited to a couple social events tonight to mingle with a couple professionals and “learn how the game’s played”. 

UPDATE

I caught the end of Dale Boger’s lecture on his most recent peptide-based natural product (the name escapes me, and I’m not around my event program at present) and entirety of Phil Baran’s.  (BTW, the short-sleeved shirt Baran wore at his presentation makes it look like he could bench-press a truck).  Keep your eye on his work, as I believe he will blow the field away with his future contributions to synthetic organic chemistry.  Of course, he synthesizes interesting targets but chooses to employ synthetic strategies that embrace functionality rather than masking it (i.e. making use of a hydroxyl group instead of protecting it with a silicon-based group).  This frame of thought is radically different to Corey’s concept of retrosynthetic analysis.  While I’m sure that many professors are currently approaching natural product synthesis from this standpoint, Baran appears to be the front running poster child for such a strategy. 

UPDATE

Why do research advisors change a functionality on their (or someone else’s) already successful ligand/catalyst/methodology (i.e. methyl to a ethyl), parade the results of a 2% increase in yield/ee/de/rate enhancement relative to previous iterations and then market their “achievement” as “novel”?  I’ve just finished sitting through 3 organic presentations and all of them have fallen into this classification (in some way, shape or form).  It’s like Honda unveiling a brand new black Accord that gets 460 mpg, has a killer 5.1 surround sound system, helicopter blades so you can fly to your destination if you don’t feel like driving (at least that’s what I’d want) and then a month later they market the exact same car except now it’s red.  I imagine these are the type of people who played hooky from ethics class in college just to sneak in round of Dungeons and Dragons before going to organic lab.  While I’m on the subject of morality, the idea of passing off percent composition as isolated yield in publishable results is criminal at best.  “Does your catalyst work?”  “Of course it does, we had 100% consumption of the starting material, ergo we’re entitled to a $5 million DOE grant.”  Do you know what also effectively gives you 100% consumption of your starting material?  (Earmuffs, EPA!)  Pouring your reaction vessel down the drain.  If you were to take a gc at t = 0 min, empty out the flask and take another gc at t = 5 min, you’d see that 100% of the starting material was consumed (watch some professor publish these results next week).  I’ve come across about 4 papers in the last month alone that reported results in a similar fashion (2 of which specifically used the word “novel” in the abstract).  

It’s been a few weeks since I’ve updated and with good reason.  I’ve submitted a draft of my first journal-worthy paper to the Boss about 2 weeks ago.  Despite the fact that he’ll probably demolish my text then remodel it to his liking, he claims to have actually liked what I reported.  But, with the success comes extra experiments to “make a stronger paper.”  To make a tired point, I’ve been running extra reactions while teaching a compacted summer course (along with grading duties).  As such, my writing has sadly slowed to a relative minimum; enough whining.  Oh, by the way, thank you to whomever posted a response about my phosphine tirade.  While the comment (for some reason) isn’t posted on the blog, I received notification from email, which prompted me to write a bit about good ‘ole organic.

I broke out an old bottle of copper(I) chloride the other day and ever since I’ve been leaving work with scrimshawed-blue calluses (I never thought I’d actually use that word in a sentence).  It turns out that copper(I), in it’s purest form, is actually colorless and oxidizes in the presence of oxygen to a blue/green copper oxide.  Ergo, as I recently purified CuCl (dissolve in HCl then precipitate the black solution with water until white) without gloves (dumb, I know), the white material I spilled on my hands during filtration eventually oxidized throughout the day.  Surely this sort of information would be extremely useful if noted in Purification of Laboratory Chemicals, but Wikipedia actually bailed me out followed by a cross-check in the Merck Index  (As a brief aside, would anyone else like to see chemical shifts reported in PoLC?)

There’s some really interesting cuprate chemistry that I’ve uncovered in recent literature searches that’s worthy of mentioning, particularly relating to conjugate reductions (an area of recent interest).  Of course, a silent majority of copper is used in conjugate additions (soft-soft interactions to all you HSAB peeps), which includes conjugate reductions using Stryker’s reagent ([Ph3PCuH]6, as seen in Org. Lett. 2001, 3, 1901-1903) or an air-stable hydrosilylating alternative (Yun’s invention, for an example, Chem. Comm. 2005, 5181-5183).  Apart from simply preparing copper hydrides from silanes (Tet. Lett. 1997, 38, 8887-8890), enantioselective variants have crept into the literature in recent years.  Here’s an interesting, yet reasonably appropriate analogy for you: Molander is to samarium chemistry as Buchwald is to enantioselective conjugate additions (check out JACS 2003, 125, 11253-11258 or Org. Lett. 2003, 5, 2417-2420, for example).  As a fairly young and naïve grad student, it’s interesting to know that Buchwald isn’t just about C-N bond forming reactions.

Does anyone know why arylsilanes work better/faster than alkylsilanes in hydrosilylating conjugate reductions?  I’m assuming it’s due to two things: (1) the electron-donating nature of an aryl ring creates a more labile hydride thus allowing for better insertion/ligand exchange with the copper and (2) the b-silicon effect seen in alkylsilanes stabilizes the cationic nature of the silicon atom making the hydride less labile.  Comments are welcome and encouraged!

As mentioned before, there’s a wide variety of conjugate additions in the literature ranging from Mulzer’s morphine synthesis (ACIE 1996, 35, 2830-2832) to Amir Hoyveda’s recent enantioselective methodologies (Org. Lett. 2007, 9, 3187-3190).  In all of the literature I’ve encountered, very few have yet to optimize an enantioselective conjugate addition of vinyl groups, which would be unbelievably synthetically useful (ORP ALERT!!!).  Apart from conjugate reductions, Evans and Johnson hammered out methodology for enantioselective Diels-Alder reactions using catalytic amounts of copper(II) and chiral ligands at low temperatures (JACS 1998, 120, 4895-4896, for example).

The majority of these reactions (with the exception of the Diels-Alder example) seem to use an excess of reagents and therefore don’t appear to be too environmentally benign.  I recall doing a copper(I)-mediated conjugate addition only to filter off the reagent during workup.  All of that precious, expensive copper gets totally wasted.  (I’ll mention that copper sulfate will complex with pyridine to pull the base out of the organic phase if your workup is acid sensitive).  Even in some of these conjugate reductions, 2 molar equivalents are used (though, it’s been demonstrated in a variety of methodologies that the mechanism is catalytic in copper) and often there’s an excess of silanes (upwards of 4 molar equivalents).  Stryker’s is no better because of the excess of triphenylphosphine, which I imagine is a pain during workup/chromatography.  Are there any benign alternatives to what’s currently out there?  (again, ORP ALERT!)

Anyone else headed to the Boston ACS conference later this month?  I’m trying to meet up with friends and colleagues in the hope of increasing my networking.  Perhaps if I come across an interesting presentation or two I’ll create a post.  Don’t really care about Barry Bonds and his 756* homeruns.  I was ecstatic about the Blue Jays, Yanks game last night when Clemens got tossed for hitting Rios (http://www.youtube.com/watch?v=-HZtiWzgT6s).  As for my Sox, we can start hitting the panic button now…

(Please don’t take my title literally)

It’s that time of year again: you don’t have a life for the next 4 weeks because you’re teaching roughly 40 h/week while trying to juggle research and getting a paper out the door (in this case, before the Boston ACS meeting).  Tensions are running a bit high, and, as a result, I’ve discovered refuge in going out for dinner/drinks with Kerri.  So, after experiencing a week of our respective families in direct contact while staring at the incoming task of a month of nonstop teaching, we headed out to the bar with a couple of friend for a few.

The New Orleans-style décor and a few rounds of drinks certainly helped, but the conversation seamlessly evolved from the Air Force and weddings to Bourbon St. and absinthe.  Often described as an “awful” but drinkable liquor, there’s lots of mystery encompassing this iconic drink.  A simple search on ebay will return results for posters with green demons, sugar spoons and herb kits.  There are numerous websites that’ll instruct you on preparing absinthe (beware, it usually takes anywhere from 2 to 4 weeks).  If you dig a bit deeper, you’ll probably find a Czech or German distributer that can get you a bottle (should it survive the voyage through US Customs). 

The US government has effectively banned absinthe for some time though (1) prohibiting the use of the purportedly “psychoactive” ingredient thujone for consumption purposes (FDA Regulations, Title 21, Chapter 1, Part 172.510) and (2) requiring that all forms of liquor distillation be licensed through the Bureau of Alcohol Tobacco and Firearms (27 Code of Federal Regulations, Part 19).  Fortunately, modern versions of the historically controversial liquor are plentiful courtesy of the internet (some that do not include the use of thujone or distillation).  Apart from the boring legal ramifications, absinthe, and more importantly, thujone, is coupled with some interesting chemistry, biologically and synthetically speaking. 

Thujone is found in many common herbs, in particular wormwoods (of the genus Artemisia) among junipers, mugwort and cedar leaf oil.  Misra and Singh reported high concentrations of a-thujone (traditionally found in absinthe at a 5 ppm concentration) in the steam distillation extracts of Artemisia vulgaris, which is native to mountainous regions of India (J. Nat. Prod. 1986, 49, 941).  While thujone carries the stigma of being “psychoactive,” (van Goth purportedly severed his ear whilst “inspired” by absinthe) researchers recently demonstrated that both thujone isomers are actually convulsants.  Casida and co-workers reported that a-thujone blocks g-aminobutyric acid (GABA) gated chloride channels during metabolism via noncompetitive inhibition (J. Agric. Food Chem. 2001, 49, 1915-1921), which (from what I gather) is a bad thing.  Interestingly, though, thujone (and its corresponding analogs) might play a role in the development of a newer, naturally occurring insecticide.  It’s been known that GABA receptors are responsible for binding insecticides (in fruitflies) and point mutation of said receptors lead to insecticide resistance (Nature 1993, 363, 449-451).

Both thujone isomers were recently determined to be radical clocks (J. Org. Chem. 2004, 69, 5684-5689) whereby ring-opening of the cyclopropyl moiety indicates a radical pathway.  Conversely, rearrangement of thujone to form the phenol carvacrol indicates a cationic path (BTW, phenols stain well on TLC plates with a 1% solution of FeCl­­3 in MeOH).  In 1971, W. S. Bowers noted the insecticidal properties of thujone, which no doubt gave rise to the preparation of a number of derivatives that are currently being studied by entomologists and chemists alike.  No doubt, both thujone isomers are also used as starting materials for natural product synthesis (Helv. Chim. Acta 1989, 72, 205-212), as thujone is a magnificent synthon for cyclopropyl moieties (clearly from a medicinal chemistry standpoint).   

Thujone is a controversial, yet very interesting molecule.  When I was recently asked to make some absinthe for experimental reasons, I promptly noted that the psychoactive effects of thujone are grossly exaggerated; you’ll clearly feel the effect of the alcohol before anything else hits you.  Nevertheless, it’s an interesting tonic that’s coupled with interesting chemistry. 

As for me and my time issue?  I’m procrastinating from setting up 3 parallel reactions that may, for all intents and purposes, prove my boss is right and I’m wrong.  Enough wasting time.  Any suggestions for future posts?

For those keeping score at home, it’s been Carbon-Carbon Bond Forming Reaction: 10, Jeremy: 0. I’ve come home the past few weeks with a sweaty forehead after my nitroethylene unexpectedly flash-polymerized in a plume of NO2 (I’ve been told by my inorganic cohorts that a little bit of NO2 is “good for ya” once in a while).  Fate has taken a turn recently, though; the University finally repaired the severed fiber optic cable behind the science library finally allowing me to use SciFinder. 

I literally stumbled onto my proverbial four-leafed clover (something that probably would’ve happened sooner had the construction crews excercised a bit more caution with the jackhammer, see above).  In the preparation of a number of nitro-containing substrates, Watanabe et al. (Hel. Chim. Acta 1984, 67, 1204-1207) disclosed that trialkylphoshpines are capable of activating already highly reactive substrates (i.e. nitroethylene) to facilitate pseudo-conjugate addition reactions via substitution mechanism.  In short, it’s a variation of the Rauhut-Currier reaction (US Patent 3,074,999 1963) or Baylis-Hillman with a twist (alkylphosphines instead of DABCO).  The best part is that the reaction mixture is pretty mild in terms of pH and therefore can tolerate a number of highly reactive olefins; the proof is seen in the new TLC spot this morning that matches up against my known standard and the fact that I haven’t seen one nanomole of nitrogendioxide gas. 

WHAT?  To the layman, think of the reaction as TNT that you’re trying to light with a match but no fuse.  You’ll inevitably blow yourself up when the match touches the highly explosive material.  Now, think of the alkylphosphine as a detonation switch similar to what Wile E. Coyote uses to blow up the Road Runner in Bugs Bunny cartoons.  This charge source is reusable and suits other major purpose of not blowing yourself up (or tanking your reaction). 

The Rauhut-Currier reaction has been applied in numerous instances.  While I won’t highlight the several applications, I will say that there’s an excellent, well-cited review about the Rauhut-Currier reaction by Michael Bultman (works with David Gin at the Sloan-Kettering Institute in NY): http://chemistry.uiuc.edu/gradprogram/chem435/fall04/07_Bultman_Abstract.pdf

Just got back from spending a few days in at Ft. Walton Beach (purportedly the “Redneck Riviera”) with Kerri.  We both ate a ton of seafood and had a great time.  The trip was surprisingly semi-inspirational as I’ve been at a research roadblock the past week or so trying to do a simple, symmetric carbon-carbon bond formation with a very unstable Michael acceptor.  I found out that the acceptor really likes to form nitrogen dioxide really easily in the presence of triethylamine.  We recently tried the lithium route but the substrate is very stubborn and won’t connect well. 

So, with my toes buried in the sand looking out on the emerald-green Gulf, I recalled doing a Michael reaction with a similarly unstable acceptor in water some time ago.  As Li reported in Aqueous Reactions in Organic Chemistry (the 2nd edition JUST came out, ISBN 978-0471761297), acrolein can installed at the alpha carbon of 1,3-diones in excellent yields using water as a solvent (demonstrated by Deslongchamps et al., JOC 2002, 67, 5669-5672).  It turns out that this method (or at least its enantioselective variant) is pretty hot in organic synthesis.  Xiao et al. recently reported on their early work on aqueous Michael additions using pyrrolidine-urea catalysts to induce enantioselectivity (Tetrahedron Letters 2007, 48, 21-24).  Other noted researchers in the field include Takabe who reported that Michael reactions in brine (particularly with reactive, easily polymerizable acceptors) actually help to stabilize the anionic intermediates thus optimizing yields (JACS 2006, 128, 4966-4967).  Interestingly enough, when his researchers used seawater as the solvent from the Pacific (they work at Scripps and Shizuoka University) they achieved similar results to using brine. 

On a side note, while the fire department was rummaging though Shelby Hall trying to find the cause of this morning’s fire alarm, Vince and I were talking about Maddox’s Titanic conspiracy that he posted a while back.  If you’re looking for a laugh, check it out: http://www.thebestpageintheuniverse.net/c.cgi?u=af07