Flow reactor syntheses of the oxazole alkaloids O-methyl siphonazole and (-)-hennoxazole A

• Applicant: Professor Dr. Malte Brasholz
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2008 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 68116605

Polymer-supported reagents have emerged as an ecologically benign alternative to homogenous reagents. Their application to organic synthesis can be regarded as green chemistry because it contributes to the preservation of natural resources and minimises the production of waste materials. Flow reactors are arrangements of linearly connected cartridges pre-packed with these immobilised reagents. An organic substrate can be eluted through such a reactor system and undergo a whole sequence of chemical transformations. The goal of this research is the production of complex target molecules using this novel technology platform. While smaller molecules have already been synthesized, the next challenge is the flow synthesis of antibiotics and antitumor agents. During recent years, the group of Professor Ley have been aiming at this vision and we consequently plan a flow synthesis of the oxazole alkaloid O-methyl siphonazole (2). We present a realistic retrosynthetic analysis of this target compound as well as a detailed plan for a flow reactor setup for its total synthesis. Following the common practice in the Ley group, we have developed a second synthesis project. We present a flexible approach to biologically active pyrrotizidine alkaloids, exemplified by hyacinthacine A5 (23). It relies on chiral butane-2,3-diacetal protected building blocks and a novel preparation of enantiopure aminoalcohols.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professor Dr. Steven V. Ley