[poonilization]

Hello, I need a little help/clarification with an assignment based on the biosynthesis of Citrinin. This may get a little messy so bear with me.

Ok so here is an image from one of my references showing the steps in the reaction. http://i.gyazo.com/8090c7213cf52cea7322133ece638fb5.png

I've drawn the mechanism/reactions of 4 malonyl CoA with acetyl CoA to form a pentaketide.
http://i.gyazo.com/b84af8607ce77ae010e5da788584fd68.png

From my references it's been stated that methylation at 3 of the carbon position occurs next. So I've drawn the enol tautomer and then drawn a reaction mechanism with the alkene attacking the methyl group on S-adenosylmethionine.
http://i.gyazo.com/ed9ccb9c449da62485107ea33b1da165.png

Ok if i've done everything correct up until now, this is where i need some clarification. In this step of the reaction http://i.gyazo.com/0b704338df9724713cb6875e4beb5829.png

Do i draw a tautomerism reaction, drawing all the ketones into their enol forms. And then do a dehydration removing an OH and a H to form the first aromatic ring shown in the step.

Then in the next step of the reaction http://i.gyazo.com/e36c72a23f1f0ead6ad85be8a208e169.png
the methyl group on the left marked with an asterisk, is that suggesting a proton is taken to form a primary anion? which would then attack the carbonly group? because it seems a bit silly to form a primary anion.

[salteen]

What you've proposed seems reasonable.  Yes, formation of the aromatic ring is likely due to a couple tautomerizations followed by aldol-type attack of the second ketone and then dehydration. 

The asterisks/squares/circles/triangles are likely just being shown to keep track of carbons (probably deduced by isotopic labeling).

[poonilization]

thanks for the reply, so i would just like to confirm one of the steps in the reaction. For this part of the synthesis. http://i.gyazo.com/e36c72a23f1f0ead6ad85be8a208e169.png

Does this mechanism look correct? http://i.gyazo.com/e36f0731c48b12e19e6e9d058a4216b9.png

I'm unsure about the primary anion, however i can't see any other way to form the ring with the 2 keto groups on it.

[salteen]

It does look a little weird when you draw it like that - the carbanion will not be stable.  How else can you represent that nucleophilic species?  Can you draw any resonance forms?

[poonilization]

Yes the negative charge can be pushed onto the oxygen, thanks i'll make a note of that in my mechanism. Is the mechanism correct though? I would have assumed the resonance form where the oxygen has the negative charge on it would attack the carbonyl carbon in a nuclophilic attack however in the reference it shows a carbon-carbon bond forming to create a ring. So i can only assume the carbanion attacks the carbonyl carbon.

[poonilization]

Also could someone explain to me what's happening in this reaction? http://i.gyazo.com/479e505bf4a3cdcf709909cb3fea22b5.png

Ok so the H on the OH group gets deprotonated, the electrons push into the C-O bond forming a C=O however that carbon is now pentavalent. So the carbon-carbon bond breaks and i'm a little confused here. How does the CH₂ group marked by an asterisk become a CH₃ group? Where does the extra hydrogen come from?

[salteen]

I would have assumed the resonance form where the oxygen has the negative charge on it would attack the carbonyl carbon in a nuclophilic attack however in the reference it shows a carbon-carbon bond forming to create a ring. So i can only assume the carbanion attacks the carbonyl carbon

The carbon does attack, through concerted electron donation of the adjacent oxygen.  I suggest you review Aldol/enolate chemistry, as this is essentially what is taking place here.

How does the CH2 group marked by an asterisk become a CH3 group? Where does the extra hydrogen come from?

If the mechanism proposed is indeed correct, there would have to be an acidic group in the active site of the enzyme catalyzing this reaction which could donate an H+ to the departing CH₂. 

As an aside, I find that step of the biosynthesis quite surprising.  I'm not sure if it's just a proposed mechanism or if it has been thoroughly demonstrated experimentally, but to me, a CH₂^- leaving group seems quite unorthodox, even with the "magic" that enzymes are capable of.  Perhaps someone with more experience in biosynthesis than I can offer more insight.