ABSTRACT
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 spirangienâ 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.
Subject(s)
Polyketide Synthases/chemistry , CyclizationABSTRACT
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.
ABSTRACT
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.
Subject(s)
Acetals/chemical synthesis , Butanes/chemical synthesis , Microchemistry/instrumentation , Acetals/chemistry , Butanes/chemistry , Equipment Design , Microchemistry/methodsABSTRACT
The syntheses of butane-2,3-diacetal protected tartrate derivatives are described using continuous flow processing techniques with in-line purification and I.R. analytical protocols.
