6-Deoxyerythronolide asymmetric aldol reaction

These highly diastereoselective aldol reactions have been used in a synthesis of 6-deoxyerythronolide B (5), which contains 10 asymmetric centers. Four aldol reactions, indicated by dotted lines, were used to construct the carhon framework with overall stereoselection of 85%.2... 

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). 

The final example illustrates yet another use of the biomimetic approach. Figure 10.9shows a retro-synthetic analysis for Masamune s synthesis of deoxyerythronolide B (213). The biosynthetic building blocks of this and other macrolide antibiotics are known to be acetate and/or propionate units combined head-to-tail, as seen in 213. 7 xhe stereocenters in 213 are clearly shown in the acyclic (seco acid) form of the macrolide 215. The specific biopathway is not utilized but rather modified to include the basic building blocks, seven propionate units (bold lines in 213).Seco acid 215 was constructed by sequential aldol condensation reactions (sec. 9.4.A) of propionaldehyde units, as shown by the disconnections in Figure 10.9. Asymmetric... 

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