Total Synthesis Of The Angucycline-type Natural Products

Angucycline-type natural products belong to the largest family of polycyclic aromatic polyketides.The core skeleton of this group of molecules always possess tetracyclic framework.And,their structural differences mainly rely on the oxidation state,substituted groups and the stereochemistry,which result the diversities of this family of natural products.Most of Angucyclines show the biological activities,such as anti-cancer and anti-bacterial.Accordingly,the synthetic and biological studies of this family of natural antibiotics will be of great significance.This dissertation mainly focuses on the total synthesis of typical Angucycline,PD-116740.A convergent synthetic route was developed by respectively preparing of the A/B and D ring fragments.Sequently,a palladium-catalyzed Suzuki-Miyaura coupling reaction was applied to connect the A/B and D rings.Sharpless hydroxylation was then employed for the introduction of the chiral diol moiet stereoselectively.After some attempt towards the optimization of the copper（II）induced oxidative coupling reaction,Cu（OH）Cl·NMI₂was selected to conduct the cyclization to generate the C ring,which could accomplish the synthesis of the A/B/C/D core tetracyclic skeleton of the Angucycline-type natural products.Herein,the total synthesis of PD-116740 was completed with 13 steps,7.5%overall yield.Additionally,the dissertation also finishes the synthesis of the sugar fragments of Xanthone.The p-toluenesulfonyl chloride was used for the activation of the deoxyoligosaccharides.The trisaccharide fragment of FD-594 was synthesized in gram scale by glucosylation of 2-deoxysaccharide in 4 steps,19%overall yield.