I had completely forgotten that today was my 2nd anniversary as a blogger until my girlfriend sent me this photo a bit earlier:
Apparently, as there were no number 2 candles (cf. last year), she instead made two cakes (possibly setting a dangerous precedent in the process!).
I can't believe that it's that time again – I've now been talking to the internet for two whole years! It's been really busy period for me in real life but in contrast a quieter one for BRSM. Although I've written 5 papers, I've only managed 44 blog posts in the past 12 months, which is unfortunately quite a bit short of the one-a-week target that I try to aim for. How people like Derek, CJ and See Arr Oh write so much decent stuff, I don't know!
I still think of this a total synthesis blog—after all, it began with me reading a Totally Synthetic post one day and thinking "I could do that!"–but it seems that the posts that get the most hits tend to be the ones based on random observations or conversations with friends. For example, here are my top posts of 2012-13 (In descending order of pageviews):
1. Where Did It All Go Wrong? – I probably wrote this in about 10 mins after glimpsing a ridiculously misassigned structure in J. Nat. Prod., but a link from Derek probably helped this to the top.
2. Drugs I Shan’t Be Taking This Week 1: 2,4-Dinitrophenol – I really have no idea why people keep reading this. It must be high on some Google search!
3. And Now For Something Completely Different 4: Wikipedia Fun – Based on the chance tea time observation that my PhD supervisor is outranked on Google by a number of golfers and DJs with the same name. I think that occasional commenter Martyn (of gyrofaunal fame) did most of the legwork for this one.
4. Superlatives 3: The Longest Polyene – A friend emailed me a photo (thanks, James!), which I posted.
5. A Birthday Surprise for K. C. Nicolaou – Inspired by a drunken conversation in a pub.
Not a single scheme in sight – I am constantly surprised by what you guys will read!
While I'm reminiscing, I'd like to thank this year's three guest authors: my long-time benefactor DrFreddy, who promised me a post 'about teenage love, the Greenwich Observatory and TNT' that he surprisingly was able to deliver; Brandon from ChemTips, who wrote about Hanessian's recent full paper on pactamycin; and Siddharth Yadav, whose post on pentacycloanammoxic acid will be up later in the week. Conversely, I also wrote my first ever guest post, which attempted to give some practical advice for the Birch reduction, over at ChemTips. I also contributed a little bit to Blog Syn, by mostly failing to reproduce other people's work. I hope that we'll find a way to get that site going again!
I'd also really like to thank everyone who has gave me advice for my imminent move to the US whether it was in person, on twitter, or via the recent mini-carnival that Jess and Freda organised. Hopefully I'll catch up with some of you one day!
Finally, thank you all for reading and commenting! I don't know what a couple of years in the US will do to my ability to spend hours messing around on the internet, but hopefully I'll keep this thing up for another year!
1. This claim would be a lot less impressive if I told you where we sent them...
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...