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Articles tagged with: macrolide

Guest Post, Still In The RBF »

[16 Jun 2011 | 29 Comments | 24,711 views]
Cyanolide A Aglycon

Rychnovsky, Gesinski. JACS, 2011, ASAP. DOI: 10.1021/ja204228q
Guest Blogger: See-Arr-Oh
When I first saw the dimeric gamma-substituted pyran motif in this molecule, I said “Gotta be Rychnovsky” (or maybe Wender).   Throughout his career at UC-Irvine, Scott Rychnovsky has been the master of the TMS-promoted diastereoselective Prins cyclization, which he has applied to the synthesis of at least 10 macrolides.  Until now, however, none have been attempted sans protecting groups!
Cyanolide A was isolated in 2010, and it’s already been the target of four total syntheses.  Perhaps this is due to …

Still In The RBF »

[30 Aug 2009 | 42 Comments | 16,673 views]
6-deoxyerythronolide B

White, Stang. Nature Chem., 2009, AOP. DOI: 10.1038/nchem.351.
Nice to see a bit of total synthesis in Nature Chemistry this month – but to be fair, this is more about the organometallics than the macrolide.  But if you’re going to prove some methodology – especially, as in this case, macrolactonisation, this is a good target to work on.  6-deoxyerythronolide B (6-dEB) is a typical polyketide macrolide, and I mean that chemically, as the configuration of the stereocenters is very much the norm.  This meant two things – …

Still In The RBF »

[25 Aug 2009 | 8 Comments | 12,537 views]
Sorangicin A – pt. 2

Smith, Dong, Brenneman, Fox. JACS, 2009, ASAP. DOI: 10.1021/ja9052366.
Read the first post?  Good.  Let’s get on with the one remaining fragment, a further DHP.  Work on this fragment was conducted via a coupling of an enone with the ready-elaborated sidechain – reaction that might be a little sluggish, as the enol functionality is again working against the group.  However, forming a cuperate of the vinyl bromide solved this, allowing a highly selective and reasonably high yielding reaction (60%, 20:1 d.r.).  BTW, the two fragments weren’t particularly …

Still In The RBF »

[23 Aug 2009 | 5 Comments | 10,726 views]
Sorangicin A – pt. 1

Smith, Dong, Brenneman, Fox. JACS, 2009, ASAP. DOI: 10.1021/ja9052366.
I thought I’d re-start after holiday with a tasty target, and sorangicin A certainly fits the bill.  It’s not often that I have to draw such an exotic structural motif into a target (though in reality it’s not far removed from a DHP); always a welcome feature in a synthesis.  But sorangicin A is more than just a structural challenge – it’s quite an antibiotic, with broad-spectrum activity against both Gram-positive and Gram-negative strains.  With the funding proposal …

Still In The RBF »

[23 Jun 2009 | 46 Comments | 16,253 views]

Jamison, Trenkle. ACIEE, 2009, ASAP. DOI: 10.1002/anie.200902079.
When a target’s been made as many times as gloeosporone, it’s a good idea to come along with something new.  And when the people you’re following have a bit of a rep, it makes it doubly necessary.  How does Seebach (twice), Fürstner, Schreiber, Ley and Holmes make you feel?  Good thing Tim Jamison’s got quite a thing for a macrocycle, and an impressive creativity with them – as demonstrated in his synthesis of acutiphycin, covered here back in 2006.  He’s …

Still In The RBF »

[10 May 2009 | 31 Comments | 12,905 views]
Amphidinolide X

Lee, Jung. ACIEE, 2009, EarlyView. DOI: 10.1002/anie.200900865.
Another month, another amphidinolide – but we’re getting pretty close to the end of the alphabet now.  Actually, I’m (as ever) being rather over-the-top – we’ve not actually covered that many, but X & Y (as well as being an affront to my ears) were blogged in 2006, where the focus was on the THF synthesis.  This is the case again with Eun Lee’s synthesis, which almost disregards the polyketide-style sections.
The key to his synthesis of the THF is a …

Still In The RBF »

[6 Apr 2008 | 26 Comments | 12,620 views]

MacMillan, Carpenter, Northrup, Chung, Wiener and Kim, ACIEE, 2008, EarlyView. DOI: 10.1002/anie.200800086.
Macrolide time again, and as this is David MacMillan, proline time too. The callipeltoside family of natural products has been reasonably popular, with syntheses from the usual suspects: Trost, Evans, Paterson, and Panek. However, all of those syntheses were of callipeltoside A, so this synthesis marks the first of callipeltoside C, including a reassignment of stereochemistry (the sugar fragment needed all is stereocenters inverted). Retro:

So far reasonably predictable/sensible disconnection – and you’ll note no …

Still In The RBF »

[13 Mar 2008 | 30 Comments | 14,737 views]

Paterson, Anderson, Dalby, Lim, Genovino, Maltas, and Moessner.ACIEE, 2008, EarlyView. DOIs: 10.1002/anie.200705565, 10.1002/anie.200705566.
Now I’ve been waiting for this ‘un… those of you who have been reading for a while will remember that I used to study at Cambridge University, and shared weekly meetings with the Paterson group. It’s certainly an ambitious target, with 21 stereocenters – and when they started the work, the absolute stereochemistry was yet to be assigned! Plenty of other groups are working on a synthesis of this beast, including …

Still In The RBF »

[3 Mar 2008 | 10 Comments | 6,782 views]

Nicolaou, Chen, Guduru, Sun, and Banerji. ACIEE, 2007, EarlyView. DOI: 10.1002/anie.200702243 JACS, 2008, ASAP. DOI: 10.1021/ja710485n.
You’d be forgiven for a feeling of déjà vu when looking at the post – yes, you have seen it before. Originally described in an Angewandte paper last year (which was discussed on this blog), Nicolaou and Chen achieved a smart, logical synthesis of the marine macrolide. The main problem was not the synthesis (which, at least from their description, was achieved without adversity), but the stereochemistry. The stereochemical …