Macrolides Evans aldol reaction

Glucolipsin A, a glycolipid possessing glycokinase-activating properties, was discovered at Bristol-Myers Squibb, but the absolute stereochemistry of the natural product remained elusive. A. Furstner and co-workers elucidated the absolute stereochemistry via synthesis and spectroscopic analysis of the natural macrolide and its Cj-symmetric stereoisomers." In their approach, they utilized the Evans aldol reaction that provided the syn aldol product with good yield and excellent diastereoselectivity. 

The samarium-catalyzed reduction was utilized in the asymmetric synthesis of the marine macrolide bryostatin 2 (42) to furnish an intermediate (46)12 (Scheme 4.21). The ketone 43 underwent an aldol reaction with the ketoaldehyde 44 via the isopinylboryl enolate to give the aldol adduct 45 in good yield and 93 7 diastereoselectivity. Subsequent samarium-catalyzed Evans-Tishchenko reduction of the (3-hydroxy ketone 45 provided the p-nilrobenzoale 46 with excellent stereoselectivity. Silylation and saponification readily converted compound 46 into the alcohol 47 in 88% yield over two steps. 

The 1,5-anti-aldol reaction was performed with chiral boron enolate of 325 and aldehyde 327, prepared by Evans asymmetric alkylation, cross metathesis, and Wittig homologation (Scheme 72), to afford 324 with a 96 4 diastereoselectivity. Stereoselective reduction of C9-ketone provided the 5y -l,3-diol, which was exposed to catalytic f-BuOK to give 2,6-cis-tetrahyderopyran 333 via an intramolecular Michael reaction. Finally, methyl etherification, deprotection, hydrolysis of ester, and Yamaguchi macrolac-tonization yielded the leucascandrolide macrolide 201 (Scheme 73). 

Miyakolide, a bryostatin-like macrolide isolated from the sponge Polyflbrospongia sp., was synthesized by Evans and co-workers using a transannular aldol reaction for formation of part of the polycyclic ring system. ... 

The reliability, scope, and ease of execution of the aldol addition reactions with acyl oxazolidinones have resulted in their extensive use in complex molecule synthesis. In Evans synthesis of the macrolide antibiotic cytovaricin (69), oxazolidinone aldol methodology was utilized to control the installation of eight stereogenic centers (Scheme 4.7) [53]. 

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