The Total Synthesis of Dragmacidins D and F

dragmacidin;heterocycle;indole;natural products;palladium;Suzuki;total synthesis

Garg, Neil Kamal ; Stoltz, Brian M.

University:California Institute of Technology

Department:Chemistry and Chemical Engineering

关键词: dragmacidin;    heterocycle;    indole;    natural products;    palladium;    Suzuki;    total synthesis;   

Others  :  https://thesis.library.caltech.edu/1058/2/Garg_Thesis_Caltech_Format.pdf

美国|英语

来源: Caltech THESIS

【 摘 要 】

The dragmacidins are an emerging class of bis(indole) natural products isolated from deep-water marine organisms.Although there has been a substantial effort to prepare the simple piperazine dragmacidins, little synthetic work has been done in the area of the pyrazinone-containing family members, dragmacidins D, E, and F.These compounds are particularly interesting due to their complex structures and broad range of biological activity.

A highly convergent strategy to access dragmacidin D has been developed.In this approach, sequential halogen-selective Suzuki couplings were used to assemble the carbon scaffold of the natural product.After executing a highly optimized sequence of final events, the first completed total synthesis of dragmacidin D was achieved.

An enantiodivergent strategy for the total chemical synthesis of both (+)- and (-)-dragmacidin F from a single enantiomer of quinic acid has been developed and successfully implemented. Although unique, the synthetic routes to these antipodes share a number of key features, including novel reductive isomerization reactions, Pd(II)-mediated oxidative carbocyclization reactions, halogen-selective Suzuki couplings, and high-yielding late-stage Neber rearrangements.

The formal total syntheses of dragmacidin B, trans-dragmacidin C, and dihydrohamacanthin A are described.In addition, preliminary studies involving a novel approach for the preparation of dragmacidin E are reported.