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Articles tagged with: HWE

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[14 Jan 2012 | 33 Comments | 23,559 views]
Fusarisetin A

Li, Deng, Zhu, Lu, Yu. JACS, 2011, ASAP. DOI: 10.1038/nchem.1196  
Just take a quick look at that target and consider that the synthetic route I’m about to summarise took thirteen steps.  I’m fairly stunned – I read the top-line number in the abstract, and immediately thought that they must have started with an advanced intermediate or degredation product, but no – the synthetic action (like many natural product syntheses) begins with Citronellal.  Sure, only three of the rings are carbocyclic, but there’s a lot going on here, so lets get into …

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[6 Sep 2009 | 31 Comments | 17,963 views]

MacMillan, Jones, Simmons. JACS, 2009, ASAP. DOI: 10.1021/ja9052366.
Now this is a popular target; I’ve covered syntheses by both Qin and Overman (with a related synthesis of vincorine by Qin too), both of which contain some really nice chemistry, and aren’t exactly lengthy.  However, this approach by MacMillan is incredibly concise, containing only nine steps, and starting with a commercially available indole.  To get to the key cyclisation precursor, a process of carbonylating the C-2 position by lithiation and addition of DMF, followed by a Horner-Wadsworth-Emmons olefination …

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[16 Feb 2009 | 17 Comments | 12,633 views]
Norhalichondrin B Pt. I

Phillips, Jackson, Henderson, Motoyoshi. ACIEE, 2009, EarlyView. DOI: 10.1002/anie.200806111. Article PDF Supporting Information Group Website

As I said in the last post, it was a rather quiet fortnight for total synthesis, at least as the big journals go. However, I think Andy Phillips can feel justified in his absence when he’s been cooking molecules like this ‘un up. Norhalichondrin B is part of the halichondrin family, isolated about twenty years ago – plenty of time for a bit of synthetic action, kicked off by Kishi back in ’92. Impressively, the synthesis hasn’t been entirely academic, with the peeps at Eisai Pharma also working on analogues. So how to start (lots of grant-application forms…)?

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[4 Jan 2009 | 27 Comments | 17,010 views]
Oseltamivir (Tamiflu) Pt. 6

Hayashi, Ishikawa and Suzuki. ACIEE, 2009, EarlyView. DOI: 10.1002/anie.200804883.
It’s back! Not just Tot. Syn., reanimated refreshed after a decent winter break, but Tamiflu too (thanks to all those who flagged this one up for me. In this case, in a (marginally) different guise, as what we’ve got here is Oseltamivir-free base, not the phosphate salt normally isolated. Not an important fact, but the salt formation probably makes quite a difference in-vivo…
However, that doesn’t matter a damn when the synthesis is a sweet at this. …

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[25 Apr 2008 | 9 Comments | 5,666 views]

Lee, Kim, Jang, Choi and Chung. ACIEE, 2008, EarlyView. DOI: 10.1002/anie.200800568.
Antibiotic… blah blah… Merck… Nicolaou… other synthesis covered…
Yep, you all know about platensimycin, and half of you have probably worked on / are working on syntheses of this ‘popular’ target. Eun Lee hasn’t bothered with a full total synthesis, instead satisfying a neat formal of the right-hand ‘cage’ motif. Key to this was the optimisation of a substrate for a rhodium catalysed carbonyl-ylide cycloaddition.
They suggest that they knew that a terminal olefin would have …

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[20 Apr 2008 | 29 Comments | 8,808 views]

Toste, Radosevich, Chan and Shih, ACIEE, 2008, EarlyView. DOI: 10.1002/anie.200800554.
Another paper from the Toste group that doesn’t use recycled Rolex watches in any of the steps. Indeed, the metal of choice today is vandadium – read-up on the methodology in this tasty JACS from 2005. Anyway, the target is octalactin A, a medium ring lactone with a bit of murine melanoma and colon tumor busting activity. Previous syntheses by Buszek, Clardy, Shiina and my boss with Andy Holmes, so it’s certainly seen …

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[10 Mar 2008 | 66 Comments | 29,694 views]

Zakarian and Stivala. JACS, 2008, ASAP. DOI: 10.1021/ja800435j.
What a beast of a molecule! This ‘un’s been around for a while, though, and has several synthesis to it’s credit – most notably that of Kishi. With a target this size, we’ve got to start with a thorough retrosynthesis. Splitting the molecule in half, separating the two polycyclic systems, the unification was planned via an alkylation of an aldehyde, which could be reoxidised for formation of the A-ring imine. RCM could then be used to complete …

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[3 Mar 2008 | 10 Comments | 6,579 views]

Nicolaou, Chen, Guduru, Sun, and Banerji. ACIEE, 2007, EarlyView. DOI: 10.1002/anie.200702243 JACS, 2008, ASAP. DOI: 10.1021/ja710485n.
You’d be forgiven for a feeling of déjà vu when looking at the post – yes, you have seen it before. Originally described in an Angewandte paper last year (which was discussed on this blog), Nicolaou and Chen achieved a smart, logical synthesis of the marine macrolide. The main problem was not the synthesis (which, at least from their description, was achieved without adversity), but the stereochemistry. The stereochemical …