Total Synthesis of the Antibiotic Kendomycin: A Macrocyclization Using the Tsuji–Trost Etherification

Abstract

A highly stereocontrolled, convergent total synthesis of kendomycin [(-)-TAN2162], an ansa-macrocyclic antibiotic, is reported. The key of the strategy is an unprecedented Tsuji-Trost macrocyclic etherification, followed by a transannular Claisen rearrangement to construct the 18-membered carbocyclic framework. The oxa-six- and five-membered rings were also stereoselectively constructed respectively by a cascade oxidative cyclization at an unfunctionalized benzylic position and using a one-pot epoxidation/5-exo-tet epoxide opening.

Stereospecific Deoxygenation of Aliphatic Epoxides to Alkenes under Rhenium Catalysis

“…Deoxygenation of epoxides into alkenes is a fundamental but important transformation in both organic and biological chemistry . Although the corresponding reverse oxygenation reactions, epoxidation of alkenes, have been well-investigated and widely applied in organic synthesis, catalytic deoxygenation of epoxides leading to alkenes has been much less developed.…”

“…This result illustrates good chemoselectivity against the silyl group as well as the wide substrate scope of the current stereospecific deoxygenation even with the sterically crowded trisubstituted epoxide. Furthermore, it is possible to protect the double bond functionality by applying the current rhenium-catalyzed deoxygenation . For example, olefin cross-metathesis following the deoxygenation (deprotection) of 3 , which was prepared by the epoxidation (protection) of geraniol, resulted in the selective functionalization of one of the double bonds with the allylic double bonds intact (Scheme ).…”

Divergent Synthesis of Bioactive Marine Meroterpenoids by Palladium‐Catalyzed Tandem Carbene Migratory Insertion

“…Scheme shows another synthesis of (+)‐8‐ epi ‐puupehedione ( 2 ). Treatment of 22 with IBX (2‐iodoxybenzoic acid) at room temperature for 2 h gave undesired product 24 in 43 % yield, as the sole product . Alternatively, 22 was treated with DDQ in a mixed solvent of CH 2 Cl 2 and H 2 O (10:1, v/v) at room temperature for 2 h; compound 22 underwent a facile ring‐opening reaction to give the desired product 25 in 62 % yield (Scheme ).…”