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Articles Archive for August 2006

Still In The RBF »

[30 Aug 2006 | 19 Comments | 9,192 views]

Rizzacasa, Bunte, Cuzzupe and Daly. ACIEE, 2006, Early View. DOI: 10.1002/anie.200602507.
A short formal synthesis of zaragozic acid C, this paper is a good reminder of the power of the Claisen rearrangement, this time in the Ireland modification. These targets were isolated in the last decade, and are inhibitors of squalene synthase, and thus have cholesterol-lowering properties. The SM shown below was made from a bit of sugar-bashing (L-arabinose), and coupling of the differentially protected unsaturated diol.

Ireland-Claisen, followed by diazomethane methyl-esterification and deprotection returned the terminal olefin, which, upon hydrogenation, cyclised …

Retrosynthetic »

[25 Aug 2006 | 5 Comments | 6,363 views]

Pérez-Castells and Gradillas. ACIEE, 2006, Early View. DOI: 10.1002/anie.2006006410.
This review article covers the ever-popular RCM step in natural product synthesis. The range of architectures is impressive, as you might expect, as is the range of ring-sizes. However, a certain theme develops as this paper contains 24, count them, reference to Alois Fürstner’s work.
However, the scope of the article is good, detailing the conditions used in each synthesis, and those condition which failed. RCM (and metathesis in general) is a relatively new field, and we as organic chemists are still getting …

Still In The RBF »

[22 Aug 2006 | 12 Comments | 6,608 views]

Gin, Kim, Wang, Navarro-Villalobos, Rohde and Derryberry. JACS, 2006, ASAP. DOI: 10.1021/ja062364i.
Amazing beast, this, and I’m using an abbreviated form! David Gin and his group have used deft control of their sugar chemistry to build this huge immunoadjuvant, containing an astounding array of functionalities. The steroid-type core is taken completely from quillaic acid, which they use as the starting point for this work. Of couse, they had to complete many glycosidations in this paper, which can look a deceptively simple coupling, but as this table shows, it can be a …

Still In The RBF »

[17 Aug 2006 | 17 Comments | 5,034 views]

Stoltz, Tambar and Ebner, JACS, 2006, ASAP. DOI: 10.1021/ja0651815
Another short but sweet synthesis by Stoltz, this time of the isopavine alkaloid amurensinine (or at least the enantiomer of the natural product). The biological activity of this target is certainly appealing enough, as it seems to be interest with regard to Parkinson’s and Alzheimer’s disease. Their synthesis involves C-C and C-H bond insertions, the former with an aryne. Lets start with a bit of C-H activation:

Okay, I guess you’ve seen this style of thing in you undergrad course, but it’s nice …

Retrosynthetic »

[16 Aug 2006 | 9 Comments | 7,932 views]

Danishefsky and Wilson. JOC – Perspective, 2006, ASAP. DOI: 10.1021/jo0610053 .
An excellent review of a great topic – development of pharmaceutical agents derived from natural products. The paper covers a broad range of substrates, but particular focus is paid to Lipitor, Paclitaxel, prostaglandins and the epothilones. If you don’t look at anything else in this paper, check out page B, Scheme 1…
Additional: As mentioned by an astute commentator, the same authors have published a related artical in Acc. Chem. Res., DOI: 10.1021/ar068018n

Retrosynthetic »

[16 Aug 2006 | 4 Comments | 5,998 views]

Peters and Fischer, ACIEE, 2006, Highlights – Early View. DOI: 10.1002/anie.200602409.
Another look at at this interesting and popular target (with a great name!) in this Angewandte Highlight. This features both the syntheses by Nicolaou and Sorensen, but doesn’t mention Snider’s intriguing efforts towards this same structure. As mentioned in a previous post, Soresen and Snider came upon a similar intermediate, attempting the same epoxidation, and both using DMDO, but to quite different results. Pity…

Still In The RBF »

[10 Aug 2006 | 24 Comments | 9,215 views]

O’ Doherty and Li. Org. Lett., 2006, ASAP. DOI:10.1021/ol061439k.
A very succinct paper by O’Doherty (no relation…) in Org. Lett. this week, showcasing his work on asymmetric hydration in a total synthesis of Milbemycin ß3. This macrolide has a huge range of activity, from antibiotic to pesticidal, so is a tempting target, exemplified by the previous syntheses by Amos Smith, Tony Barrett and Phil Kocienski amongst others. The principle disconnection left them with a spiroketal unit and a remote stereodefined methyl group to consider, which they tackled with some interesting methodology.

Very …

Retrosynthetic »

[8 Aug 2006 | One Comment | 4,244 views]

Phillip Broadwith. Daily Telegraph, 2006, August 08.
Okay, a bit off-topic again, but congratulations to my lab-mate Phillip, who won this years Telegraph / Bayer Science Award for scientific writing (in the 20-28 year old category). He wrote a great article about olefin metathesis that was published in this UK national newspaper today (you can read it here). Bringing metathesis (and dancing) to the masses!

Still In The RBF »

[8 Aug 2006 | 7 Comments | 4,742 views]

Boeckman, Pero, and Boehmler. JACS, 2006, ASAP. DOI:10.1021/ja063532+.
A masterclass in the use of chiral auxiliaries, Boeckman et al. have used this synthesis to showcase the power of the camphor lactam chiral auxiliary. A potent target, rasfonin is cytotoxic to cells dependant upon the protein, Ras, a known oncogene; however, other cell lines are unaffected by rasfonin at ten times the IC50. So certainly a valid target. As inferred above, their approach utilises campor lactam chiral auxiliaries rather heavily, and start with an interesting elaboration of …

Editorial »

[4 Aug 2006 | 21 Comments | 4,227 views]

I know, it’s not chemistry, but interesting things are brewing over at Nature. You see, they’re changing their peer-review process, and adding a new option for authors (so far only for Nature Chemical Biology edit: actually, only Nature just now). It’s currently working as a blog, where one can comment as on the Sceptical Chymist. This is the “open review” process, and clearly means that the sample-size of their referees has grown hugely. But the demographic of those lauding or critisisng the work has also changed to a more web-literate …