Macrolide aglycons

The combination of the (S)-enolate 2 with aldehyde 1 is one of the key steps in the syntheses of the macrolide aglycone 6-deoxy-erythronolide B131 and tylonolidc16. 

M. Roddis, P. Gates, Y. Roddis, J. Staunton, Structural elucidation studies on 14- and I6-membered macrolide aglycones by accurate-mass ESI sequential MS, J. Am. Soc. Mass Spectrom., 13 (2002) 862. 

In an earlier ehapter in this series (Volume 1, Chapter 13) written twenty years go, one of us compared the exercise of a complex synthesis to a tortuous journey "that continually asserts the unpredictability of travel through all but the most familiar terrain." And that was a chapter describing a synthesis of the Prelog-Djerassi lactone Onward travel to methynolide, the simplest of all the macrolide aglycons, seemed like a daunting task for its time. It is a measure of the distance synthetic organic chemistry has come in the past two decades that we can now plan and execute routes to the most complex macrolide structures found in nature, albeit with a blueprint that usually requires many steps and at a level of overall efficiency that removes practical value from the sequence in most... 

Masamune [91]. It is recognized as particularly relevant in the context of stereoselective aldol reactions. Masamune developed the chiral ketones (J )-and (S)-179, derived from each enantiomer of mandelic acid, to conduct dia-stereoselective aldol reactions with both achiral and chiral aldehydes (Scheme 4.19) [91-93]. Subsequent to aldol addition, desilylation and oxidative cleavage of the chiral controlling group provides a carboxylic acid. The synthesis of the macrolide aglycon 6-deoxyerythronolide B (187) showcases the use of these ketones and represents the first successful application of double asymmetric induction in the context of a complex target [91, 93, 94). 

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