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!!!
A busy week in the lab trying to finish this damn natural product. More things at the weekend.
Update 30/07/11: Forgot to give a reference for the Hoffmann paper, which is Angew. Chem. Int. Ed., 1993, 32, 101-103. It's not a bad piece of work, and was for a time the shortest route, despite being entirely linear.
Johann Mulzer, one of my favourite chemists, wrote a review back in 1991 titled 'Erythromycin Synthesis—A Never-ending Story?'. It's well worth a read as these natural products have inspired an awesome body of work, and were an important benchmark in stereoselective natural product synthesis for many decades. Woodward, Stork, Corey, Danishefsky, Evans, Paterson, Reinhard Hoffmann, Mulzer, Carreira and most recently White have all worked on them, which is some recommendation.
Anyway, I was reading Hoffmann's synthesis of (9S)-dihydroerythronolide A today when I encountered a most unusual set of conditions for deprotection. To set the problem in context, the (unstable) triply protected compound below had been obtained, and only three steps remained to the glorious completion of the target; selective cleavage of the cyclopentylidene acetal, macrolactonisation (assisted by the conformation limiting p-methoxybenzylidene acetals) and a final deprotection. The problem was that the cyclopentylidene acetal couldn't be removed without cleaving the other protecting groups, despite encouraging results obtained earlier in model studies. Not wanting to start again, a method to slow down hydrolysis of the p-methoxybenzylidene acetals was needed.