title: Highly stereoselective total synthesis of fully hydroxy-protected mycolactones A and B and their stereoisomerization upon deprotection.
abstract: Unprecedentedly efficient and highly (≥98 %) stereoselective syntheses of mycolactones A and B side chains relied heavily on Pd-catalyzed alkenylation (Negishi version) and were completed in 11 longest linear steps from ethyl (S)-3-hydroxybutyrate in 12% and 11% overall yield, respectively, roughly corresponding to an average of 82% yield per step. The synthesis of mycolactone core was realized by using Pd-catalyzed alkenyl-allyl coupling and an epoxide-opening reaction with a trialkylalkenylaluminate as key steps. Fully hydroxy-protected mycolactones A and B of ≥98% isomeric purity were synthesized successfully for the first time. However, unexpected 4:3-5:4 inseparable mixtures of mycolactones A and B were obtained upon deprotection.
authors.affiliation: Herbert C. Brown Laboratories of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907-2084, USA.
authors.forename: Guangwei
authors.initials: G
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Yin
authors.forename: Ei-ichi
authors.initials: E
authors.lastname: Negishi
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D001427:Bacterial Toxins / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry*; D018942:Macrolides; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D001427:Bacterial Toxins; D007783:Lactones; D018942:Macrolides; C117218:mycolactone; C451488:mycolactone A; C451489:mycolactone B