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.

 

(+)-Sch 725680

(+)-Sch 725680

Organic Letters, 2012, 14, 4303-4305

Toshifumi Takeuchi et al.

The retrosynthesis of (+)-Sch725680, begins with disconnecting the ester bond, thus giving acid chloride 13 and alcohol 10 as the main components.  Alcohol 10 comes from an hydroxyl addition on to a carbon-carbon triple bond in alkyne 9.  (Synthetically this is accomplished by just acidic treatment of the in-situ generated alcohol on the conjugated triple bond).  Compound 9 comes from an Aldol-condensation of ketone 8, which is generated by (a) alkyne lithium addition on aldehyde 6,; (b) methyl lithium attack on Weinreb amide portion of the molecule and finally,; (c) oxidation of the alcohol formed to the ketone functionality by using PCC.  Compound 6 comes by ring-opening of lactone 5 by N, O-dimethylhydroxylamine hydrochloride and oxidation of the primary alcohol.  The protected alcohol 5 comes from diol 4, which is formed by a cyclization of terminal alcohol on the chiral auxiliary 3.  Compound 3 is generated by a titanium mediated aldol reaction of imide 1 with aldehyde 2.