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sciencebeard

A blog about chemistry, biology, and everything in between.

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sciencebeard

I am a PhD candidate in the School of Chemistry at Trinity College Dublin, from which I also received my B.A (Mod.) in Medicinal Chemistry. See my about page for more info.

Total Synthesis Blog: Lycoricidine

The Sarlah lab this week published the total synthesis of two isocarbostyril alkaloids1, lycoricidine and the closely related narciclasine, impressively starting from the quite cheap commercially available bromobenzene. Both products have useful biological properties2, but as always the utility of natural products lies in their availability. The latest synthesis obviates reliance on Stille-type couplings3 (and the organotin reagents that come with them), further cementing its utility.

Structures

Fig 1. Structures

The Sarlah et al. synthesis begins with generating the cis-dihydrodiol through a modified Sharpless reaction, the Naraska-Sharpless dihydroxylation. Using the arenophile MTAD with visible light illumination, followed by osmium tetroxide and NMO (as one would usually see in Upjohn and Sharpless procedures) the team introduces the aryl boronic acid to obtain the bicyclic adduct. The researchers at the University of Illinois then utilised a quite nice Suzuki coupling with their boronate ester, using Pd(dppf)Cl2 as a catalyst. The boronate ester likely ‘fragments’ in a sense, and the aryl bromide and boronic acid act in the Suzuki, transposing to yield the diol. Diol protection as the acetonide follows using 2,2,-dimethoxypropane in the presence of the pyridinium salt of p-toluenesulfonic acid, PPTS. This enables the base hydrolysis of the methyl ester to the relevant acid.

First synthetic section

Scheme 1.

They make the call to install the required amino-alcohol through a nitroso Diels-Alder. In order to line up deprotection of the resulting amide nitrogen, the team used a TIPS-protected reagent in the nitroso Diels-Alder. This furnishes the 1,4-syn product with good stereocontrol following a dissolving metal reduction with zinc and acetic acid. To finish off, a one-pot oxidative cleavage using the hypervalent iodine (III) reagent, PIFA, followed by exhaustive acetonide deprotection with trifluoroacetic acid yields (±)-lycoricidine.

Second synthetic section

Scheme 2.

Where the paper really comes into its own is the transformation into narciclasine following the nitroso Diels-Alder – but to see how they do it, check out the published work (DOI: 10.1002/anie.201709712). Displaying increased atom economy and yields relevant to earlier work, the Sarlah approach facilitates analogue synthesis from readily available starting materials.

References

  1. E. H. Southgate, D. R. Holycross and D. Sarlah, Angew. Chem. Int. Ed. Engl., 2017, 56, 15049–15052.
  2. a) T. Okamoto, Y. Torii, Y. O. Isogai, Chem. Pharm. Bull. 1968,
    16, 1860–1864; b) G. Ceriotti, Nature 1967, 213, 595; c) G. R.
    Pettit, V. Gaddamidi, G. M. Cragg, J. Nat. Prod. 1984, 47, 1018;
    d) S. Ghosal, S. K. Singh, Y. Kumar, R. S. Srivastava, Phytochemistry
    1989, 28, 611.
  3. H. Zhang and A. Padwa, Org. Lett., 2006, 8, 247–250.
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Playing God

If you could wipe out a whole species, would you?

If I asked a room of 100 people what their fears are, there’s a pretty high chance I would get answers like “spiders” and “snakes” as a high percentage. So the question I pose is; if we could choose a species or family from the family tree to wipe of the planet, would you?

The two members of the animal kingdom mentioned above might give some people the heebie-jeebies, but the fact is that they each are a fundamental part of a food chain, functioning in their own ecological niche. Wipe out spiders for example, and several bird and reptile species would soon follow as the food web the spiders cling to is sent crashing down.

However their may be a family that can be completely eradicated without any serious repercussions, and furthermore their removal from the biosphere could save millions of lives.

Continue reading “Playing God”

GM-Oh? The Future of Farming

When you Google search the phrase ‘GMO’, you’re met with a a plethora of images showing needles injecting unnamed chemicals into the skin of fruits, protest images and other mock-ups involving Frankenstein’s monster-like vegetables. The phrase ‘Franken-food’ in big red letters on a black background is thrown at you. While these images are (quite frankly) hilarious, they are also inherently damaging and cause hindrance to important genetic research. Unfortunately, as with most popular science topics highlighted in the media, there’s a lot of ambiguity surrounding GMOs and many people have no idea what they actually are.

Continue reading “GM-Oh? The Future of Farming”

Blacker than Black – Novel ‘Nano Art’

I’ll stop wearing black when they invent a darker colour

– Wednesday Addams

Even with our fairly narrow perspective on the electromagnetic spectrum, most people would say that they know their colours. A red car is red, a green plant is green and a black shirt is going to be black regardless of the circumstances. Right?

Continue reading “Blacker than Black – Novel ‘Nano Art’”

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