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Articles tagged with: Claisen

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[30 Oct 2011 | 38 Comments | 20,380 views]
Daphmanidin E

Carreira, Weiss. ACIEE, 2011, EarlyView. DOI: 10.1002/anie.201104681   
Now that’s a busy polycyclic ring-system!!  Three five-membered rings, two six-membered rings and one seven (depending, of course, on how one counts the ring sizes.  Anyone read the IUPAC Gold Book last night?) – adding up regardless of maths to one hell of a synthetic challenge.  And there’s even some token biological activity to aim for – this bad-boy has some moderate vasorelexant acitivity next to rat aorta.  (When the paper mentions ‘moderate’ activity, we can be pretty sure it does very little indeed…) …

Still In The RBF »

[18 Jan 2010 | 16 Comments | 16,394 views]
Hyperforin

Shibasaki, Kanai, Shimizu, Shi, Usuda. ACIEE, 2010, EarlyView. DOI: 10.1002/anie.200906678. ; Shibasaki, Kanai, Kuramochi, Usuda. Org. Lett., 2004, 6, 4387. DOI: 10.1021/ol048018s. 
Three amazingly tough targets completed in (almost) as many months – you can’t tell me that total synthesis is stifled.  Hyperforin has been staining the white-boards of many a lab for decades – the isolation (reported in Antibiotik…) was way back in ’71, and has resisted synthesis until now.  Shibasaki himself has been working on it for quite a while, as you’ll have seen in the header – a key …

Still In The RBF »

[10 Nov 2009 | 19 Comments | 14,437 views]
Rubromycin

Brimble, Rathwell, Yang and Tsang ACIEE, 2009, EarlyView. DOI: 10.1002/anie.200903316.
Now for something rather different… indeed, we’ve only got one stereocenter in rubromycin, and the synthesis is racemic.  However, one of the toughest and most commons lessons learnt when moving from total synthesis to medicinal chemistry is ‘just cause it’s flat, doesn’t mean the synthesis is easy’.  Frankly, rubromycin is a bitch to make, and has attracted many a chemist to their folly (seventeen papers referenced by Brimble here…).  However, tricky as it is, it’s not impossible – both Danishefsky …

Still In The RBF »

[20 May 2009 | 22 Comments | 14,271 views]
5-epi-vibsanin E

Davies, Williams, Schwartz, Denton, Lian. JACS, 2009, ASAP. DOI: 10.1021/ja9019484.
Now that’s a substituted ring…  done and dusted by Huw Davies and Craig Williams as a collaborative effort (I’d quite like to know how this worked, as the two groups are quite removed), with Davies weighing in with some smart chemistry for building seven-membered rings.  This clearly critical to the synthesis of such a molecule, but the challenge is the heavy substitution, which has thwarted several groups (including individual efforts).  Whilst this paper doesn’t complete the …

Still In The RBF »

[10 Mar 2008 | 66 Comments | 29,376 views]

Zakarian and Stivala. JACS, 2008, ASAP. DOI: 10.1021/ja800435j.
What a beast of a molecule! This ‘un’s been around for a while, though, and has several synthesis to it’s credit – most notably that of Kishi. With a target this size, we’ve got to start with a thorough retrosynthesis. Splitting the molecule in half, separating the two polycyclic systems, the unification was planned via an alkylation of an aldehyde, which could be reoxidised for formation of the A-ring imine. RCM could then be used to complete …