I don't like to apologise too much for things I do (or more often don't do) on here, because, well... it's not like you pay me anything. That said, I am sorry things have been so quiet around here for the last couple of months. It's been a hectic end to my postdoc, but I'm able to kick back for a couple of weeks at least before I head over to the USA. I'll try and write a few posts before then. And after. In the meantime, here's a talk I wrote for a group meeting at the start of the month on the topic of Felkin Ahn selectivity. We've been revising 'basic' topics, and I was amazed how much I've forgotten Maybe this'll be useful to someone.
Yes, I did steal that image from Dave Evans' notes...
Here it is: Substrate Control in Acyclic Systems BRSM (2 mb)
Update 03/04/2013: Chemjobber made a few!
Thanks to a recent xkcd comic I've just discovered a wonderfully concise new way to communicate – non-overlapping Venn Diagrams:
For example, here's a statement my boss made last week expounded thus:
I quite enjoy the contradiction between the visual simplicity of displaying information in this way and the fact that it's actually a lot more effort to construct these than write a sentence that conveys the same information, as well as their highly inefficient use of space. There's just something kind of amusing about them. Or I think so, anyway.
Give it a go, and share any good (chemistry related) ones you can think of in the comments. I've just put one in a talk I'm writing on acyclic stereocontrol for a group meeting; I'll let you know how that goes down next week!
Most of the credit for this one goes to occasional commenter Martyn!
Is it just me, or will green chemistry journals publish anything these days? For example, check out this paper published this morning in the Journal of Sustainable Agitation:
Unpowered Mechanical Stirring of Reaction Media Using Renewable Stirring Fish (RSFs). [PDF]
I couldn't make this stuff up!
Okay, this second post is a lot later and a fair bit shorter than I had hoped it would be, but it's been a crazy and not entirely pleasant month. Enjoy!
In the previous Woodward Wednesday post I showed you guys the first half of Woodward's epic total synthesis of the popular bioactive natural product reserpine. If you didn't catch that when it came out, go and check it out, because I'm just going to carry straight on where it left off. Here goes!
Sorry things have been so quiet around here; it's been a hectic month! Here's something silly born of an unusual conversation over coffee.
The office microwave: unnecessary chemophobia?
The Merck Index, along with Fieser and Fieser's Reagents for Organic Synthesis, Greene’s Protective Groups, March’s Advanced Organic Chemistry and Amarego’s Purification of Laboratory Chemicals is one of those books that any self-respecting organic research group will have a copy of. It’s an iconic reference work, although its usefulness has definitely waned in recent decades with the rise of the internet, Scifinder/Reaxys/Chemspider and Wikipedia. As Derek reported before Christmas, it was recently acquired by the RSC, who have just released an updated edition. I mostly use mine to pass the time waiting for NMRs to run, or when I need a more reputable reference than Wikipedia for a paper or report. However, all of that changed last week when a tea break conversation sparked a bizarre new game: The Merck Index Challenge.
Anyone who’s ever flicked through a copy will probably have noticed that amongst all the drugs, solvents, salts and plants there are a number of… aberrant… entries. For example, Whiskey. And Lard. And Raspberries. And Quorn. And Milk. Thus, the question arose: could a meal be constructed using only ingredients from the Merck Index? Better yet, could one manage three courses?
To mix things up a bit, I've traded posts with Brandon from Chemtips, who's going to be telling you a bit more about Hanessian's pactamycin work in this special guest post. If you head over to his blog you can read my advice to anyone attempting a Birch reduction. Anyone else interested in guest blogging here or swapping posts, please contact me! Enjoy! -BRSM
Today’s target, pactamycin, is an excellent example of just how creative evolution can be. Densely functionalized and almost unique (the authors put forward several loosely related structures), this Streptomyces metabolite is characterized by six contiguous stereogenic centres. First isolated in the early 1960’s, pactamycin binds strongly to the 30S fragment of the ribosome and is toxic to both mammalian and bacterial cells . Briefly considered a potential anticancer agent, the natural product was ultimately shelved over safety concerns.
The first total synthesis of pactamycin was published by Hanessian et al. in Angew. Chem. Int. Ed. Eng. back in 2011, but I’m going to base most of this post on a follow-up publication in J. Org. Chem., which details some of the trials and tribulations encountered during the long synthesis . The ACIE paper has also been discussed over at Synthetic Nature.
I'm going to do this one in two parts, in the hope that posting the first half now will force me to find time to write the second part at the weekend. Also, it'll hopefully make for shorter and more readable posts. Enjoy!
Reserpine is an indole alkaloid isolated in 1952 from the extract of Rauwolfia sepentina or ‘Indian snake root’, a popular plant in traditional Indian medicine used as a sedative and antipyretic, and reportedly taken by Mahatma Gandhi himself. It's also enjoyed some attention from Western doctors as an antihypertensive and antipsychotic, notably being the first ever drug to successfully demonstrate antidepressant properties in a randomized placebo-controlled trial (although it’s rarely used nowadays because of its numerous side effects, which are as varied as they are unpleasant). Its structure was solved in just 3 years (a remarkably short period for the pre-NMR era) and, when it was finally reported in the summer of 1955, Woodward immediately set to work. By the end of 1956, just a year later, he was able to report a detailed series of studies culminating in the landmark first total synthesis of the natural product, again pushing forward the complexity limit at which synthetic chemists could operate. In the years that followed, reserpine became a classic target, worked on by some of the greatest chemists of the past 50 years. In fact, it remains a popular molecule to this day, as indicated by a new total synthesis reported just a month or so ago by Jacobsen and co-workers, (Org. Lett., 2013, 3, 706).
Although Woodward’s synthesis of this target, supposedly his personal favourite of all those he masterminded, has been discussed in just about every book to be written on the history of total synthesis, I can’t resist the temptation of writing my own summary of it any longer, so here goes.
From Chem. Commun., 2013, ASAP (DOI: 10.1039/C3CC38271K)
Seriously. From the abstract:
"Self-supporting superconducting replicas of pasta shapes are reported, yielding products of differing 3D architectures. Functioning high-temperature superconductor wires are developed and refined from replicas of spaghetti, demonstrating a unique sol–gel processing technique for the design and synthesis of novel macroscopic morphologies of complex functional materials."
Huh? And it gets better in the 'General Experimental' section:
"Spaghetti (own-brand durum wheat dried pasta) was purchased from The Co-operative Food (Co-operative Group Limited, UK), penne and fusilli (own-brand durum wheat dried pasta) were purchased from Sainsbury’s (J. Sainsbury’s plc, UK) and HonigTM Samen “Piraten Pasta” was a gift from Jamie Shenston (University of Bristol, UK) and Caroline Walker (Heinz)... Unless stated otherwise, all materials were used as received, and with no further purification."
The pasta is then soaked in a delicious blend of yttrium, barium, copper and silver (until green), oven baked at 920 ºC (gas mark 36, if you're trying this in your oven at home), sintered and annealed to taste then served in liquid helium. Yum!
Thanks to occasional commenter Martyn for pointing this out!
I'm a little busy with blog-syn and actual work at the moment, but a friend just sent me this screenshot from the Aldrich website, which I think I'll share with you all (annotation his):
Now, correct me if I'm wrong, but if I wanted to report a compound in, say, J. Med. Chem., I'm quite sure that TLC would not be an acceptable proof of purity. And if anyone knows how I can TLC quantitatively, please leave a comment, because I'm getting sick of running all these crude NMRs and HPLCs...
As some of you might remember, towards the end of last year DrFreddy over at Synthetic Remarks offered out his services as a guest blogger to anyone interested, purely for the fun of blogging somewhere new for a change. I took him up on his kind offer, and this post is the result. Anyone else interested in writing a guest post (or having me write one) should get in touch. Enjoy!
When I first came to London I was only sixteen
With a fiver in my pocket and my ole dancing bag
I went down to the dilly to check out the scene
And I soon ended up on the old main drag
That's the first verse of one of the best songs ever written and performed.
When I was seventeen (not sixteen — and it wasn't my first time in London — but still), me and my then girlfriend went on a weekend trip to London. It was awesome in every aspect. Unfortunately, I can't bring back every detail of it today, and for that I blame the synergistic effects of ethanol and teenage love (CAS # 51-61-6) on your central nervous system. One thing, however, will never be forgotten — and I still possess the physical proof (vide infra).
On the Sunday morning, we took a boat out to the Greenwich Observatory. By the way, did you know that is was we Vikings who first named the place? Anyhoo, apart from literally standing at the center of time and taking in every revelation that comes with it, we got hungry. So, we started looking for a place to eat. Mind you, this was in the early '90s, and large tracts of Europe were still not perfectly adjusted to a free market economy, so every street corner was yet to be blessed with a 7-Eleven (True story, kids!). It turned out that we couldn't find a single open pub or restaurant or any place that would sell us something edible. But, on one street we found open store. Antique books.
I love old books, it's not that. But when you are hungry, slightly hung-over and your teenage love deserves a meal, your main priorities might be elsewhere. However, our return boat was another hour away, so I decided to check the place out anyway. My girlfriend waited outside. In anger.
I made it quick. I came out with this.
For the record:
Title: Practical Chemistry
Authors: Bruce and Harper
Publisher: Macmillan and Co Limited
Publication date: 1947
It set me back 50 pence, and I decided to just take it before flipping it open. Its pocket size, the nice patina and the word "chemistry" on the cover; good enough.
Back in Stockholm, Sweden several weeks later was probably the first time that I gave it a real chance. Little did I realize then that this was hands down the best investment I had made in life so far (and maybe to this day). Also, that it would strongly contribute to choosing the path that led to who I am today, for good or bad.
This little one had everything. First, I read it. Then I read it again. Before I knew it, I had memorized every page. I set up a laboratory in my boy room. It grew bigger and crazier by the day, and my risk assessments were in hindsight not stainless.
I'd like to wrap this story up with a confession: Yes — I did at one time synthesize TNT according to the recipe presented. On the kitchen stove, no idea of what I was really doing, a late night when my parents were away, in a 500 mL Erlenmeyer flask, into a boiling mixture of concentrated nitric and sulfuric acids went a squirt of toluene, and out came eventually a yellow solid that stained your fingers upon touching it, and judging by ocular inspection, in a total yield of a few milligrams (<1 %).
What is the best investment of your life so far?
Written by Fredrik von Kieseritzky who blogs as DrFreddy at Synthetic Remarks
 Kind of a stretch admittedly, since I likely have very little real Viking DNA in me.
 In this context, I should probably say "shop." — And maybe consider putting the closing quotation mark before the damn period. No! Full stop... aarrgh....
 I just consulted with a lawyer friend of mine, who uttered the magic phrase "statute of limitations." Still everyone — do not try this at home!!!