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(±)-11-O-Debenzoyl tashironin   

15 December 2006 5,116 views 10 Comments


Danishefsky, Cook, and Polara. JACS, 2006, ASAP. DOI: 10.1021/ja0670254.

A very quick synthesis of this compact yet complex natural product, abliet in it’s racemic form. Danishefsky et al. decided to use a rather impressive oxidative dearomatization to construct one ring, allowing a further intramolecular Diels-Alder reaction to complete the core. But they had to make the cyclisation substrate first:


Functionalisation of the aromatic ring was completed easily, with a formylation and bromination of a m-hydroxy-phenol delivering the electrophilic Stille component. Coupling to an allyl silane, and elimination of a mesyl group then finished the cyclisation substrate, which was treated with phenyliodine-(III) diacetate (PIDA):


Good job! Completing the natural product really took no effort took relatively few transformations; Prilezhaev reaction produced only the desired epoxide, and the exocyclic double-bond was reduced with Wilkinson’s catalyst. Opening of the epoxide with superhydride and oxidation/deprotection then returned the target. Nice work!

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  • chemist says:

    I would say that “completing the natural product really took no effort” is an understatement. In fact, the completion of the synthesis was as challenging as the development of the cyclization itself (and, probably, even more challenging). For example, they tried to use Me instead of Bn, but couldn’t cleave former and had to repeat the entire synthesis for the Bn version.

  • Tot. Syn. says:

    You are quite right; I’ve rephrased that statement to what I actually meant. Serves me right for writing a post after a few beers…! However, I don’t recall reading about the methyl / benzyl ether problem – is that in the paper? Methyl ethers are notoriously hard to remove, so I’m not entirely surprised that they had a bit of bother.

  • ranfiddler says:

    It’s a nice synthesis.
    “Prilezhaev reaction produced only the desired epoxide”. Huh? I guess the reaction actually was not easy to control. It may not be surprising to deliver an alpha-epoxide. The regioselectivity was hampered by steric hindrance. The low isolated yield was expected. Another question is, if the methyl was installed instead of the terminal alkene, the allene substrate will behavior differently? What I thought about the biomimetic strategy could be rather different. Nature may form the C5-C6 at last as Fukuyama proposed in 1995 (TL).

  • I had to look up the Prilehaev reaction. I was rather underwhelmed to discover it’s just a peracid epoxidation of an alkene, and for all my chemistry years I have neglected to recognise this valuable contribution by name. In future I will endeavour to bamboozle my colleagues by referencing him.

    So as not to make an arse of myself, any ideas how you pronouce that? Pril-E-Hi-eff?

  • PS Danishefsky – he’s the man!

  • Tot. Syn. says:

    I notice that too, but I couldn’t help myself but use the named reaction term! I knew you folks would look it up and go “Huh?!”.

  • Antediluvian says:

    It’s a thing of beauty. Not much room for retrosynthetic analysis there :).

  • Chemist of Sorts says:

    Nice work! I have to comment, though, on the phrase “abliet in it’s racemic form”. In my mind this does not detract from the synthesis in the least. Academics obsess about enantioselectivity and, while certainly important, it is the strategy I find fascinating in a synthesis like this. Enantioselectivity, presumeably through formation of the allene selectivity, would seem to be more of an methodology advance and add relatively little to the synthetic accomplishment.

  • Buckgopher says:

    There is already alot of methodology out there for creating allenes selectively. During the alkyne addition they just could have added BINOL (just like they say in the paper) to make the alcohol selectively. Then during the SN2′ only one allene would form.

  • dtb says:

    ^ Not so sure about that… I’m sure Danishefsky and co. would have tried adding BINOL at least once, and would have made the target enantioselectively if they could. I wouldn’t be surprised to find that the addition of BINOL resulted in isomerisation of the delta,gamma-unsaturated aldeyhde – from my own (limited) experience with similar species, they’re nightmarishly prone to isomerisation.