B.R.S.M. Yield isn't everything

13Jun/131

Guest Post: Pentacycloanammoxic Acid

Today's guest post is from Siddharth Yadav, an enthusiastic young chemist from somewhere in India. Enjoy!

 

I found B.R.S.M. when I was searching the web for the synthesis of cubane by Philip Eaton and was much delighted by the way the material was presented and interpreted, although a quick glance through B.R.S.M. showed me that this blog is not actually centred on compounds like cubane but rather on natural compounds (with their asymmetric carbons and stuff). So, I decided to write up a post on a compound that is much strained like the unnatural compounds but is indeed a naturally occurring chemical – pentacycloanammoxic acid.

Fig 1

It all started when a guy named Damste discovered some unique lipids in some rare bacteria known as ‘Anammox’ (derived from Anaerobic Ammonia Oxidation) bacteria. These tiny guys oxidize ammonia and nitrite ions to liberate nitrogen gas and water, but during this conversion they produce hydroxylamine and hydrazine; two very damaging and membrane permeable intermediates! So as an SOS, these guys have a lipid bi-layer made of pentacycloanammoxic acid, which is denser than average membranes (dense enough to keep hydroxylamine and hydrazine at bay; hence avoiding their diffusion into the cytoplasm and preventing cellular damage).

Now to the really interesting part – structural determination of this ‘unique’ lipid gave a rather odd looking architecture! In fact they found two such lipids with slightly different structures. Much to the delight of the synthetic community; E. J. Corey and Vincent Mascitti jumped on the challenge for a total synthesis for pentacycloanammoxic acid. Any guesses why Corey and Mascitti didn’t choose the other acid?

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5Mar/1312

Guest Post: Pactamycin (Hanessian, 2012)

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

Pactamycin Structure

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 [1].  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 [2].  The ACIE paper has also been discussed over at Synthetic Nature.

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29Jan/132

Guest Post: 50p

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?[1] 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.[2] 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.

Practical Chemistry

For the record:

Title: Practical Chemistry
Authors: Bruce and Harper
ISBN: ?
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.

TNT recipe

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 %).[3]

What is the best investment of your life so far?

Written by Fredrik von Kieseritzky who blogs as DrFreddy at Synthetic Remarks

 

[1] Kind of a stretch admittedly, since I likely have very little real Viking DNA in me.

[2] In this context, I should probably say "shop." — And maybe consider putting the closing quotation mark before the damn period. No! Full stop... aarrgh....

[3] 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!!!

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