Study On The Synthesis Of The Natural Products Of The

A practical and economical approach to benzoquinone ansamycin antibiotics was described.The all-purpose C8-C15synthon was synthesized based on Sharpless asymmetric dihydroxylation and Katuski asymmetric epoxidation. Weinreb-CBS protocol was employed to introduce the aromatic ring and construct the C15stereogenic center. The C1-C7fragment was prepared in7steps from a commercial available chiral pool material using easy chemistry. Assembly of the target molecule was then achieved in5steps including a zincate mediated coupling of the two pieces in a diastereoselective manner. At last, the total synthesis of Herbimycin A was accomplished in19linear steps and4.2%yield.In addition, on the strength of Weinreb-Deoxygenation protocol, the C11-C21fragment of Geldanamycin was obtained in9steps and24%overall yield. Thus, the versatility of this approach which could be utilized in the synthesis of all benzoquinone ansamycins was demonstrated.Instead of utilizing the sensitive and expensive chiral-reagent, this route emphasizes the use of catalytic asymmetric reactions to construct the challenging stereogenic centers. Furthermore, the aromatic ring was introduced at the late stage, which endows the route with convergence. The concise skeleton-construction strategy and the facile access to stereogenic centers made the strategy applicable in deep-seated SAR exploration and structure modification.