Fragment Synthesis Of Autolysin And Study On The Ring-closure Metathesis Of High Hindered Olefins Promoted By Hydrogen Bonding

Autolytimycin is a novel polyketide macrolactam that was originally isolated from the culture of Streptomyces Autolyticus JX-47 in Yunnan soil Streptomyces at the beginning of this century.This material consists of aromatic phenol and ansa-bridged macrocyclic lactams that contain six stereogenic centers and two(E)-tri-substituted ethylenic bond.The ansamycin antibiotics,including the Hsp90 disrupter geldanamycin,are a family of aromatic-containing ansa-bridged macrocyclic lactams that possess a tremendous range of antitumor activities.Autolytimycin,one representative of the phenol type benzenic ansamycin is a promising lead compound with excellent physical and chemical properties.The needs to solve it's the scarcity of resources has captured the organic chemist's attention in an effort to study on structure-activity relationship of autolytimycin.In this dissertation,we have reviewed the development in research of synthesis of benzenic ansamycin and(E)-2,4-dimethylbut-2-en-l-ol-containing fragment.The main works done that can lay a foundation for total synthesis of Autolytimycin and main content as follows:we have defined a synthetic pathway to the C3-C7 fragments of Autolytimycin and both of model and non-racemic C9-C15 fragments of Autolytimycin was prepared via four different strategies of protecting groups,Which can be performed on the decagram scale and multigram-scale laboratory preparation respectively,The third-generation the synthesis of C9-C15 fragment of the autolytimycin was accomplished in 11 steps(17.09%yield,Using the strategy of O-Bn and O-TBDPS protective groups)starting from commercially available 2,3-O-isopropylidene-D-glyceraldehyde.The fourth-generation of the synthesis of C9-C15 fragment of the autolytimycin was accomplished in 11 steps(22.2%yield,Using the strategy of O-TBS and O-TBDPS protective groups)starting from commercially available 2,3-O-isopropylidene-D-glyceraldehyde;A novel and efficient methodology for ring closing metathesis reactions promoted by hydrogen bonding mediated catalysis have been developed.In this paper,computation result from Semi-Empirical Molecular Orbital Methods and so forth also show that hydrogen-bonding can promote demanding Ring-Closing Metathesis.This efficient methodology may pave the way for total synthesis of Autolytimycin and construct tri-substituted olefins via hydrogen-bond-promoted ring closing metathesis reactions.