Synthesis of bioactive natural products and analogues

Abstract: Natural products have until recently provided the only remedy for treatment of diseases. The development of modern chemistry in the last centuries has opened the door for tapping into the chemical diversity found in nature. Synthetic natural products, together with analogues, are an important piece in the puzzle towards curing many ailments. In this thesis, synthetic endeavors towards different biological targets are presented. A plant derived cannabinoid was synthesized and shown to have nociceptive properties in mice, by activating the TRPA1 receptors in the spinal cord, without having any activity on the cannabinoid receptors. Chronic obstructive pulmonary disease (COPD) is a growing health problem and the cytokine thymic stromal lymphopoietin (TSLP) has been shown to play a key role. By semisynthesis of TSLP inhibitors, a structure activity relationship study was performed in order to find new TSLP inhibitors, which leave the bodily defense systems intact, and help persons with asthma or COPD. Parasitic illnesses often lack efficient treatments, thus a total synthesis of pulchrol and pulchral, natural antiprotozoal benzochromenes, and the preparation of a library of analogues for a SAR study, is presented. Furthermore, a synthetic effort towards the total synthesis of the plant metabolite pulcaffeate is presented, a compound that also has been shown to possess antiprotozoal activity. By targeting different biological systems, new compounds are developed and tested, In the case of the synthesis of the bioactive benzochromenes, this led to the finding of a method for synthesizing either benzochromene or fluorene compounds from a common starting material. This could possibly be of interest for the synthetic organic chemists in the future.