Now today we're going to learn a little
bit about uh this molecule here. This uh
crazy complex looking piece of molecular
architecture which is called strickening
which no doubt you probably well have
heard of. It's a well-known poison.
These days it's used for killing rats
but in the past it was a medicinal
compound especially in the Victorian
area. So at that point in time uh it was
used for all sorts of ailments like
headaches. It was a one of the very
first athletic performance enhancers,
believe it or not. And of course, it's
it's a poison. It's really not useful in
any of these respects whatsoever. It
comes from the the seeds of a tree in
the Philippines. And over hundreds of
years, the Filipinos had used the
extracts of this bean, as they called
the seed, to treat various ailments. So,
it was a a sort of herbal type of
medicine. And it works on the nervous
system. So it'll give you a bit of a
tingle. Um obviously in high doses or or
actually not that high doses um it it
will have very severe effects on you.
But if if something you take something
interacts with your body, you get a bit
of a tingle and perhaps you feel it like
it's doing good rather than harm. So in
small quantities uh it it was used for
centuries but actually it's got no real
beneficial effect as a medicine. And
indeed, you know, famously it's been
used uh in all sorts of murder mystery
cases. I have just one story about
stricken, but I really like
it. Just before I started as a PhD
student, a Brazilian professor visiting
the chemistry
department took some stricken out of the
store because he wanted to poison his
wife. But being a professor, he was a
bit absent-minded and he mislaid the
scritnine. He lost it and he got really
worried that somebody might get poisoned
other than his wife. So he went to the
police and admitted
everything and then the stricken was
found in his jacket pocket hanging in
his
wardrobe. So his wife was safe. What
happened to the professor? I have no
idea. One of the founders of Stanford
University was poisoned by Strickling,
murdered by Strickling, and her last
words were that this is the most
horrible and painful death. In fiction,
it's been used a lot. Agatha Christie,
three or four novels of hers had
stricken in in the Grand Budapest Hotel.
It's in there as a as a poison.
Actually, there hasn't been many deaths
or murders through the use of
strickening uh luckily. So this was uh
given to us by Sigma Aldrich uh for the
use in uh the periodic videos. So thank
you very much to them. Yeah, there's
about a gram in here and it takes about
10 to 50 mg to to kill a human being.
This tree gives beautiful white flowers.
Uh very fragrant smelling. Um but
presumably it's in there to stop animals
from eating the seeds. You know, the
animal takes a bite of it and doesn't
finish its meal. Like many of the
compounds that I talk about, it works on
the nervous system. means that your all
your muscles go out of control and you
know you die of aphixxiation of uh not
being able to breathe because your lungs
aren't working properly. Imagine it is a
series of electrical cables with
junction boxes in between and at the
ends you got sensors and muscles at the
other end. So sensors build up using
ions a concentration of of positive
charge using generally sodium,
potassium, calcium ions that then fires
an electrical charge down the the cable
to the other end and then calcium ions
allow the release of neurotransmitters
to go and tell the muscle or the brain
or whatever is on the other end what to
do. So this interferes with that process
at the junction boxes. Uh so this
inhibits uh both sodium and chlorine ion
channels which is unusual. Normally a
molecule will interact with just one
type of receptor whereas this this
interacts with two types of receptor.
How does it actually get there? Yeah,
that's a good question. So if you ingest
something, it will go obviously into
your your gut. Once it's in the gut, it
can then pass through the gut to blood
barrier. It needs to be charged to do
that. So we got a basic amine on here.
It then gets into your bloodstream and
the bloodstream then transports it
around your body. this uh obviously with
the blood will go to all your muscles
and start to interfere with any uh
neuromuscular junctions that that it
comes across. It's not a very good
murder weapon because it will stay in
the body for years, traces of it. So,
it'll be very easily identifiable.
[Music]
No, it's a new one to us.
What does stricken taste like? Um well
they say it tastes bitter and uh on
stricken uh there's this tertiary amine
here this this blue atom uh and anything
with a tertiary amine always tastes
incredibly bitter. A lot lot of insects
have uh these tertiary amine molecules
on on the back so that they taste
horrible. So a bit like um licking a
brass or copper spoon. Yeah. Really
bitter and
h really not very pleasant at all. So
again, not not the best poison cuz you
you're going to taste it in your cup of
tea.
Here we are. We'll open the bag. Yeah.
The uh high security containment system
and just take a a little look at what
stricken looks
like. So there we have the top. There's
not a lot in here actually. I was maybe
maybe 100 milligrams. Not not a gram at
all.
Let's just take
that. There we
go. So, there we go. Just a a
white powder essentially. Looks fairly
innocuous. I mean, the majority of
chemicals that we work with are not
toxic. Uh that maybe it was so-called
harmful, maybe slightly corrosive. The
majority are not that way at all. I
wouldn't want my PhD students to to work
with anything that's extremely toxic. Um
although we have made a few natural
products over the years which which are
really quite potent but this is quite
dangerous substance and and not
something that the likes of which we
would normally be working with. I look
at that and I think wow that's
beautiful. Such a a really unique
architecture. All of these ring systems,
you've got hydrogens pointing into this
cavity here. Seven membered rings, five
membered rings, six membered rings, all
sorts of different molecular
architectural pieces in there. And for
the synthetic chemist, that makes this
an absolutely outstanding challenge.
This is the Everest, if you like, of the
total synthesis type of world. So, it
was
isolated by two French chemists in 1818.
So, you know, nearly 200 years ago now.
Uh, and it was about 120 years later by
the time chemists had figured finally
figured out what on earth the structure
was because it's just so
complex. So, there were over 100 250
papers attempting to find out what the
structure of stricken was. And
eventually in 1947
uh two chemists uh Robert Robinson who
was later became Sir Robert Robinson at
Oxford University he proposed the
correct structure and uh Luke's and and
a completely separate chemist also did
but Rob Robinson was very famous in his
day and this was a culmination of of two
decades worth of work in his
laboratories. Seven years later, Robert
Burns Woodward was the first uh group to
synthesize it. And uh Robinson had said
for its molecular size, it's the most
complex molecule ever known. Since
Woodward's original synthesis, there's
been 17 further synthesis. So 1954 was
the first synthesis. There's around 28
synthetic steps, so different things
that you had to do. And the yield was
minuscule. It was uh they were starting
from tens of kilos and getting milligs
out.
O00006% yield which is a very small
amount and and quite a lot of steps 28
steps actually is for the the complexity
of this molecule is still quite
competitive. The next synthesis was uh
carried out in 1992. So it was you know
many years later uh by Philip Magnus
that was again 28 steps but he he got it
up to 0.03% 03% yield. Considerably uh
more efficient, about a thousand times
more efficient, but still a very low
yield. In each case, um all of these
people uh were developing a new type of
bond connection connecting reaction and
they were putting that into operation.
So Magnus in in his synthesis was making
this bond and this bond in the key step
using a deal's order type of reaction.
uh Woodward had used uh um obviously the
the synthetic chemistry of the day and
in you know 40 years had passed by the
time Magnus uh came to doing it in 1994
was the next synthesis and that went and
went up to 3% yield using Larry
Overman's chemistry and these are all
you know incredible these are the the
rock stars of the organic chemistry
world that are coming to play here. Uh
so uh time moves on 2007 Padra got it
down to 16 steps 2% yield by 2011 we had
the shortest synthesis ever nine steps
by Chris Vanderval terrible yield there
was one really difficult step in there
but nine steps when you think the
original was 28 um it's quite incredible
and probably the best synthesis out
there is by David McMillan 12 steps but
6% yield so considerably stronger 10,000
times more efficient than the original
synthesis and this is the progress that
organic chemistry has made not only in
structural elucidation. So 20 years
worth of work in the 1930s and 40s 250
papers to determine the structure of
this. Today one of my PhD students would
be able to determine the structure in an
afternoon because spectroscopic
techniques have have come an incredibly
long way. There were almost none back in
1946. We had infrared. There was an
X-ray of this in 19 52. So that was one
of the very first X-rays, but in 1946
that didn't exist. So back then they had
to uh literally chemically react it and
figure out what uh bonds would have been
broken through that uh type of reaction.
So it was a real detective story back
then using evidence, chemical evidence
to determine structure. Whereas now we
can use spectroscopy. What's going to
happen to that now? Well, I'll put some
of that back in the bottle and the rest
we'll have will destroy and then what
it'll sit on a shelf for a rain. It will
sit in a lock cupboard. Yeah. Just in
case we get some rats in the uh the
labing. Uh but every few seconds your
brain's saying breathe in, breathe out,
breathe in, breathe out. It it does it
automatically or or move your muscles.
So if you stop any of those signals,
then obviously your muscles stop. And if
you stop breathing, you're going to die
pretty quick.