Total synthesis of kendomycin: a macro-C-glycosidation approach.
Kendomycin, also known as (-)-TAN 2162, is a novel polyketide-derived ansamycin isolated from Streptomyces sp., which exhibits potent antagonist and agonist activities at the endothelin and calcitonin receptors, respectively. This bacterial metabolite also possesses a strong antibiotic activity against a range of gram-positive and -negative bacteria and cytostatic effects on the growth of human cancer cell lines. When a novel macroglycosidation reaction is employed as the key step, the first enantioselective total synthesis of kendomycin has been accomplished. A Friedel-Crafts-type ring closure of the acyclic precursor containing tetrahydropyran and benzofuran moieties produces the macrocycle as a single stereoisomer in good yield, thus establishing the aryl C-glycosidic linkage of the ansa core. This reaction requires a phenolic glycosyl acceptor and appears to proceed through a rapid O-glycosidation followed by a slow rearrangement to an aryl C-glycoside. The requisite secomacrocycle is prepared by the Pd(0)-catalyzed B-alkyl Suzuki-Miyaura cross-coupling of two subunits, which in turn can be expeditiously assembled from readily available building blocks in a modular fashion.
Yuan
Yu
Y
Department of Chemistry, Princeton University, Princeton, NJ 08544-1009, USA.
Men
Hongbin
H
Lee
Chulbom
C
D006027:Glycosides / Q000737:chemistry*; D017828:Rifabutin / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry
D006027:Glycosides; C485395:kendomycin; D017828:Rifabutin