Ripostatin A

 

Ripostatin A

Org. Letters 2012, 14, 4690

W. Tang & E. V. Prusov*

The retrosynthesis of Ripostatin A begins with a deprotection of the protected methyl acetal which quite sensitive.  This was achieved by a mild neutral aqueous hydrolysis.  The terminal acid functionality was derived from oxidation of the primary alcohol by Dess-Martin periodinane oxidation followed by Pinnick Oxidation (sodium perchlorate).  The alcohol was originally in its TBS-protected form in 8.  Predictably, the central alkene group in 8 was formed by a ring-closing-metathesis reaction using Grubb’s second generation catalyst. The double allyl groups required for the RCM reaction were neatly installed by a double Stille reaction between allyl stannane 5 and double-vinyl-iodide compound 6.  Conceptually, this is really interesting as it reduces the need to install the two carbon-carbon-double-bond groups separately.  The ester group of compound 6 is the next disconnection giving rise to acid 5 and alcohol 4.  The ketal group of 4 comes from the open ketone 3, which is prepared by an Patterson Aldol reaction between methyl ketone 2 and aldehyde 1.  The syntheses of both 1 and 2 have been described by the authors in their previous publication Angew. Chem. Int. Ed. 2012, 51, 3401–3404.