Total synthesis of (−)-(6R,11R,14S)-colletallol via proline catalyzed α-aminoxylation and Yamaguchi macrolactonization

A simple and efficient synthesis of 14-membered macrolide (−)-(6R,11R,14S)-colletallol was achieved in a highly diastereoselective manner using proline catalyzed alpha-aminoxylation and Yamaguchi protocol.

An enantioselective total synthesis of Sch-725674

An enantioselective total synthesis of Sch-725674 using dithiane alkylation, cross metathesis reaction, Yamaguchi macrolactonization and a substrate controlled stereoselective reduction as key steps is described.

Glycal approach to the synthesis of macrolide (−)-A26771B

A convergent synthesis of macrolide natural product (−)-A26771B starting from d-glucal is reported. Key features of this synthesis involve Ferrier rearrangement, cross metathesis of chiral fragments 3 and 4 and Yamaguchi macrolactonization.

Carbohydrate-based first stereoselective total synthesis of bioactive cytospolide P

A facile stereoselective approach has been developed for the total synthesis of cytospolide P via Yamaguchi macrolactonization.

A macrolactonization approach to the total synthesis of the antimicrobial cyclic depsipeptide LI-F04a and diastereoisomeric analogues

The cyclic peptide core of the antifungal and antibiotic cyclic depsipeptide LI-F04a was synthesised by using a modified Yamaguchi macrolactonization approach. Alternative methods of macrolactonization (e.g., Corey–Nicolaou) resulted in significant epimerization of the C-terminal amino acid during the cyclization reaction. The D-stereochemistry of the alanine residue in the naturally occurring cyclic peptide may be required for the antifungal activity of this natural product.

The Sammakia Synthesis of the Macrolide RK-397

The polyene macrolide RK-397 3, isolated from soil bacteria, has antifungal, antibacterial and anti-tumor activity. Tarek Sammakia of the University of Colorado has described (Angew. Chem. Int. Ed. 2007, 46, 1066) the highly convergent coupling of 1 with 2, leading to 3. The preparation of 1 depended on the powerful methods that have been developed for acyclic stereocontrol. Beginning with the allylic alcohol 4, Sharpless asymmetric epoxidation established the absolute configuration of 5. Following the Jung “non-aldol aldol” protocol, exposure of 5 to TMSOTf delivered the aldehyde 6 in high de. Condensation of 6 with the lithium enolate of acetone also proceeded with high de. The resulting alcohol was protected as the MOM ether, to direct the stereoselectivity of the subsequent aldol condensation with 8. Selective β-elimination followed by reduction and protecting group exchange then gave 1. The preparation of 2 took advantage of the power of Brown asymmetric allylation. Allylation of the symmetrical 11 led to the diol 12. This was desymmetrized by selective acetonide formation, to give 13. Ozonolysis, reductive work-up, and protection of the newly-formed 1,3-diol gave 14, setting the stage for oxidation and asymmetric allylation to give 15. Reductive deprotection and oxidation then delivered the acetonide 2. The tris acetonide 16 was assembled by addition of the enolate derived from 1 to the aldehyde 2, followed by reduction and protection. Kinetically-controlled metathesis with 17 established the triene 18. Phosphonate-mediated homologation to the pentaene 19 followed by hydrolysis and Yamaguchi macrolactonization then completed the synthesis of the macrolide RK-397 3.