Catherine F. Carter

Accelerating Spirocyclic Polyketide Synthesis using Flow Chemistry

Over the past decade, the integration of synthetic chemistry with flow processing has resulted in a powerful platform for molecular assembly that is making an impact throughout the chemical community. Herein, we demonstrate the extension of these tools to encompass complex natural product synthesis. We have developed a number of novel flow-through processes for reactions commonly encountered in natural product synthesis programs to achieve the first total synthesis of spirodienal A and the preparation of spirangien A methyl ester. Highlights of the synthetic route include an iridium-catalyzed hydrogenation, iterative Roush crotylations, gold-catalyzed spiroketalization and a late-stage cis-selective reduction.

A breakthrough method for the accurate addition of reagents in multi-step segmented flow processing

In order to use segmented chemical flow processing in more complex reaction sequences, a method has been developed to precisely control the addition of reagent streams during multi-step operations. Using in-line infra-red monitoring with a new LabVIEW software application, it is possible to control additional pumps to dispense further reagents in real time based upon the concentration of reaction intermediates. This enables precise mixing with perfect timing thus greatly increasing product quality and enabling segmented chemical flow processing to be used in extended reaction sequences.

Diastereoselective chain-elongation reactions using microreactors for applications in complex molecule assembly.

Diastereoselective chain-elongation reactions are important transformations for the assembly of complex molecular structures, such as those present in polyketide natural products. Here we report new methods for performing crotylation reactions and homopropargylation reactions by using newly developed low-temperature flow-chemistry technology. In-line purification protocols are described, as well as the application of the crotylation protocol in an automated multi-step sequence.

The continuous flow synthesis of butane-2,3-diacetal protected building blocks using microreactors

The continuous flow synthesis of butane-2,3-diacetal protected derivatives has been achieved using commercially available flow chemistry microreactors in concert with solid supported reagents and scavengers to provide in-line purification systems. The BDA protected products are all obtained in superior yield to the corresponding batch processes.