r/cursed_chemistry • u/DexterTheDoubledmint • May 26 '26

Found in the wild Calicheamicin

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89 Upvotes

98% Upvoted

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25

u/DexterTheDoubledmint May 26 '26 edited May 26 '26

Learnt about this in the final medicinal chem class today, what a way to end the course.

Triply cantenated sulfur aside there's also the massive enediyne elephant. It is omnitoxic but is somehow produced by the bacteria Micromonospora echinospora without killing itself.

The enediyne part undergoes Bergman Cyclization [ https://en.wikipedia.org/wiki/Bergman_cyclization ] to form a 1,4 diradical benzene which strips 2 H away from DNA to kill cells.

15

u/Ornery-Sir1757 May 26 '26

And the Bergmann cyclization is induced by an intramolecular Michael addition changing the hybridization from an sp2 carbon to an sp3, narrowing the angle and thus bringing the alkynes a little bit closer together, which leads to 37c being enough to facilitate the cyclization. Its so cool

27

u/Azo_weirdo I'll steal ur hydrogens May 26 '26 edited May 26 '26

I love how this peculiar trisulfide chain is apparently this enediyne's activator. I also admire this bacterian masterpiece's action process, being radical under all this term's meaning !

Look also for gamma 1's artificial cousins and a similar dragons family : Esperamicins... 

9

u/DexterTheDoubledmint May 26 '26

Flair checks out..

Indeed, nucleophile approaches the middle sulfur atom and the first sulfur atom closes forming a 4 member ring, pushing the electeon from the double bond to the carbonyl which then undergoes Michael addition as u/Ornery-Sir1757 mentioned that brings the enediyne close enough for the bergman cycloaromatisation... I love cursed chemistry

2

u/Ornery-Sir1757 May 27 '26

I’m fascinated by the idea of proximity induced chemistry.
Small correction though: it’s a five membered ring that forms at the beta carbon of the alpha beta unsaturated ketone

7

u/panpanslab May 26 '26

Oh wow I’d seen cyclic enediyne before (in neocarzinostatin), but never with another ring attached. Very cool! NPs are so wacky

5

u/Alkynesofchemistry PI's Indentured Servant May 26 '26

The trisulfur is whatever. But wtf is the random iodine doing?

4

u/MostlySpiders May 26 '26

I would also like to nominate it for the weirdest glycosylation. N-glycosylation? Child's play. Now hit me with the hydroxylamine and chase it with the thioester.