B.R.S.M. When all you have is a hammer everything looks like a nail


Cyanthiwigins B, F, and G

Total Syntheses of Cyanthiwigins B, F, and G

Stoltz et al., Chem. Eur. J., 2011, Early View; [PDF] [SI] [GROUP]

DOI: 10.1002/chem.201100425

I briefly contemplated not covering this, as I covered the Stoltz group conquest of liphagal last month,[1] and this uses the same palladium-catalysed enantioselective decarboxylative alkylation as the key asymmetry creating step. However, this is such a clever and powerful demonstration of the methodology that I couldn't help myself.[2] This time the targets are the cyanthiwigins, a family of marine diterpenoids with over 30 members, all sharing a highly conserved 5-6-7 tricyclic core. The few members isolated in sufficient quantity for testing, and the cyathanes in general, have demonstrated a range of biological activities so new routes to these compounds could be useful.

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A second post this weekend - you guys are lucky the weather is awful here!

Total Synthesis of (+)-Omphadiol

Romo et al., Angew. Chem. Int. Ed., 2011, Early View; [PDF] [SI] [GROUP]

DOI: 10.1002/anie.201102289

Omphadiol is an africanane sesquiterpene isolated for the first time in 2000 from a basidiomycete. No-one knows what it does because of the small amounts isolated, but structurally similar sesqui- and diterpenes exhibit various biological activities including antiviral, anti-inflammatory and anti proliferative effects. It’s also got an interesting 5-7-3 ring system and 6 contiguous stereocentres around the ever popular trans-hydroazulene core. That notwithstanding, it took Daniel Romo and coworkers at Texas A&M University just 10 steps (and not a single protecting group) to prepare the natural product stereoselectively from (R)-carvone via a bicyclic b-lactone intermediate. 

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Schindilactone A

Here's an impressive total synthesis of schindilactone A by Tang, Chen, Yang,[1] and 14 coworkers. At 29 steps in the longest linear sequence that's comfortably fewer than two per author. Still, the route is entirely linear and it's a fairly heroic effort, as we'll see.

Work began sometime ago as the group published syntheses of the ABC (Org. Lett., 2006, 8, 107) and FGH (Org. Lett., 2005, 7,885) fragments of the slightly more complex micrandilactone A some time ago. Apparently that unique, ketal spanned, 7-8 carbocyclic system in the middle took some time to work out. I'll cover the older work on those fragments as well, as it shows the origins of some of the key steps in the schindilactone A total synthesis.

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(+)-Loline Alkaloids

2330 - update: Just noticed the Tot. Syn. writeup. Check it out for an alternative discussion! Funny that this work's two weeks old, yet we both write about it today!

An Efficient Synthesis of (+)-Loline Alkaloids

D. Trauner et al., Nature Chemistry, 2011, 3, 543 [PDF][SI][GROUP]

DOI: 10.1038/nchem.1072

I just noticed this very efficient enantioselective synthesis of a trio of the loline pyrrolizidine alkaloids reported by Trauner and coworkers back in June. Although loline has been known for more than a century, prior to this work only one enantioselective synthesis had been reported, and at 20 steps in length - that's well over two synthetic operations per carbon atom - it's as good an example as any to illustrate the point that size isn't always what makes a target challenging. Trauner, with characteristic German efficiency, took only 9 steps to reach loline through clever use of some simple and largely well established chemistry. Reading this paper reminds me of one of the most important axioms for designing anything (syntheses, websites, software, machinery...): that a thing should only be as complicated as it needs to be - and no more.

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