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Articles Archive for May 2007

Still In The RBF »

[31 May 2007 | 23 Comments | 7,891 views]

Cossy, Ferrié, Reymond and Capdevielle. Org. Lett., 2007, ASAP. DOI: 10.1021/ol070670a.
Another synthesis of this popular target, and whilst not mind-blowing, certainly a nice strategy for one of my favourite targets. However, I should point out that the synthesis is actually only a “formal”, as they didn’t bolt-on the oxazole sidechain. Rather, they focused on the macrolide core, using three allylations and a crotylation to install four of the hydroxyl units.

The rest of the molecule was constructed using a metathesis to add the ester unit to the top …

Still In The RBF »

[25 May 2007 | 33 Comments | 10,027 views]

Nicolaou, Sarlah and Shaw. ACIEE, 2007, Early View. DOI: 10.1002/anie.200701552.
I wasn’t planning on putting this synthesis up today; in fact, I’ve got a tasty number from Steve Ley to put up. However, one glance at the palladium cascade in this paper left me with my jaw on the floor, and I’d started transcribing the structures before I knew it! So, a quick look at the biological activity would be in order: selective inhibitory activity against HIV replication in H9 lymphocytes (EC50=0.798 μg) with a TI of about 31.3, …

Still In The RBF »

[21 May 2007 | 23 Comments | 9,967 views]

Macherla, Manam, McArthur and Potts. Org, 2007, ASAP. DOI: 10.1021/ol0706051 .
This target has certainly seen it’s share of interest, and you certainly know it’s an interesting target if industry decide to make it! Indeed, this paper is by some folks at Nereus Pharmaceuticals, San Diego, who were clearly interested in its 20S proteasome busting activity (read inhibition). Although there have been several syntheses of Salinosporamide A, the group state that they needed a route suitable for analogue generation – apparently that beta-lactone is a bit of …

Meta »

[18 May 2007 | 8 Comments | 4,280 views]

Many of you will have noticed that I have a forum on this site; if you haven’t, it’s accessible from the link above. However, I’ve a had a bit of trouble with spammers, so I’d closed new regisrations for quite a while. Since then, though, I’ve opened up registration again, and hope things clean up a little.
So if your got something on your mind, chemistry or not, then head on over!

Still In The RBF »

[16 May 2007 | 38 Comments | 6,860 views]

D. Kim, Park, B. Kim, H. Kim, and D. Kim. ACIEE, 2006, Early View. DOI: 10.1002/anie.200700854.
Again with the medium rings! And what a target – I’m still surprised to see that bromo-allene in a natural product, but nature is known for her surprises… This time, however, the focus isn’t really on the eight-ring, but on the six, with a slightly tricky bromide to introduce.
The starting point for the synthesis was a Grignard addition into an aldehyde, setting up the stereochemistry from a chiral aldehyde. Formation of the …

Still In The RBF »

[14 May 2007 | 14 Comments | 4,634 views]

Takahashi, Doi, Iijima and Takasaki. JOC, 2007, ASAP. DOI: 10.1021/jo062546v.
At first, I loved the look of this synthesis; take one really simple acyclic precursor, dump in a little of everyone’s (or at least my) favourite palladium catalyst, and hey-presto – instant 5,5-spiro fused ring system. However, after that reaction, things go off-the-rails a little…
The substrate, as I said, was made very quickly, doing a double Tsuji-Trost allylic alkylation with the bis(phenylsulfonyl)methane on two allyl halides (okay, one is an allyl acetate…). They were then set to cyclise, using the same …

Still In The RBF »

[7 May 2007 | 77 Comments | 35,454 views]

Nicolaou. ACIEE, 2006, Early View. DOI: 10.1002/anie.200604656.
Nope, it’s not done yet (slackers…), but there’s a very interesting KCN penned piece in Angewandte this week as an essay on the structure of Maitotoxin. It’s certainly been an intimidating challenge for the synthetic community for sometime, but with a molecular weight of 3422 g-1mol, LD50 of 50ng (yes, nanograms… I read a paper that states “a gram of maitotoxin can kill
approximately half a billion mice”), and nearly 100 stereocentres, it’s going to take some doing. Interestingly, there may be a flaw in …

Still In The RBF »

[3 May 2007 | 35 Comments | 13,668 views]

Feng, Tian, Yuan, Mu and He. Org. Lett., 2007, 9, 2019. DOI: 10.1021/ol070597o.
Bear with me on this one – I guess you’ve seen this target before. I was shown this paper by a few of the chaps in our group, and was just astounded with the transformation, and even more by the mechanism.

Awesome! But the mechanism contains some rather worrying steps. I’ve capture the entire thing directly from the supp. info., cause even I can’t be bothered redrawing that:

(The supp. info., BTW, is here.)
I’m particularly concerned by the Fe-mediated …