Well here we are in what is arguably the slowest month to get through, being skint after the excesses of Xmas. Anyway this week’s ASAP is a contribution from the Kirschning group at the Leibnitz University in Hannover and deals with the total synthesis of Elansolid B1 and was published in Organic Letters.

This compound and others of this family of polyketides all show antibiotic activity, especially interesting is the activity against methicillin-resistant Staphylococcus aureus and Micrococcus luteus.

Several prominent reactions were utilised in the construction of elansolid b1: An intramolecular Diels-Alder cycloaddition, producing the bicyclo[4.3.0]nonane ring system,  two Sonogashira reactions to install two of the double bonds via acetylene reduction, not forgetting the Evans (syn) adol reaction, a Grignard reaction and a Yamamoto aldol.

An interesting point here is the use of a benzyldimethylsilyl group as a masked phenol:

After Grignard addition the resulting alcohol is re-oxidised to the ketone. Liberation of the phenol under mildly acidic conditions allows generation of the p-quinone methide. The attack of nucleophiles then only occurs at the re face, because the se face is blocked by the two methyl groups thus achieving complete selectivity.

Another problem that was elegantly solved was the selective reduction of the di-acetylene to produce the Z-E-Z triene.

Several systems were investigated for the acetylene reduction to the Z double bonds. As may be expected the central double bond was also reduced as was the terminal acetylene, the other being subjected to steric crowing was less reactive. A carefully optimised Zn(Cu/Ag) alloy was finally found that carried out the desired conversion, exact details can be found in the supplementary material.

This is an interesting biomimetic approach to this class of antibiotics and I recommend it to you as a synthesis packed with lots of useful information. Good reading.