Synthesis of C13-C25 fragment of 24-demethylbafilomycin C(1) via diastereoselective aldol reactions of a ketone boron enolate as the key step.
An efficient synthesis of the C13-C25 fragment is described for 24-demethylbafilomycin C1, a new member of the plecomacrolide family isolated from fermentation broth of Streptomyces sp. CS which is a commensal microbe of Maytenus hookeri. The targeted C13-C25 fragment possesses five oxygenated and three methyl-substituted stereogenic centers. It is obtained through formation of the C17-C18 syn aldol by using an ethyl ketone boron enolate with diastereomeric ratios of 95:5 and 83:17, respectively, for the chiral aldehydes substituted with acetoxy and methoxyacetoxy groups at C15. The results confirm the observation that the stereochemistry at C22 of the ketone is determinant to the diastereoselectivity of the aldol reaction. The synthesized C13-C25 fragment having a methoxyacetoxy group at C15 is considered as a useful precursor for construction of the 16-membered ring lactone of 24-demethylbafilomycin C1 through an aldol condensation of the methoxyacetate followed by formation of the C12-C13 double bond via a diene-ene RCM reaction.
Guan
Yucui
Y
Laboratory of Asymmetric Catalysis and Synthesis, Department of Chemistry, Zhejiang University, Hangzhou 310027, China.
Wu
Jinlong
J
Sun
Liang
L
Dai
Wei-Min
WM
D000447:Aldehydes / Q000737:chemistry; D001895:Boron / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry*; D005030:Ethylenes / Q000737:chemistry; D007659:Ketones / Q000737:chemistry*; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism
C522529:24-demethylbafilomycin C; D000447:Aldehydes; D005030:Ethylenes; D007659:Ketones; D018942:Macrolides; D002244:Carbon; C036216:ethylene; D001895:Boron