Center of Excellence on Environmental Health and Toxicology (EHT)
| In summary, a novel synthetic method for the preparation of substituted indanes was successfully developed via the Lewis/Brønsted acid-mediated cyclization of the E-stilbenylmethanols followed by nucleophilic transfer from trialkylsilyl reagents. The reactions gave the products in good to excellent yields with excellent diastereocontrol; the products were exclusively trans at the C1-C2 position. However, the nucleophilic transfer proceeded with only moderate to good diastereoselectivity. A small library of indolobenzazocinone was synthesized by using developed method involving ring annulations of various dihydroisoquinolines with azlactone and Pd-catalyzed C-H amidation which could accomplish the target molecule in just two steps. This lactamization protocol provides a new synthetic route which was performed initially for the biologically active compounds and also capable of constructing a wide range of related compounds with different substitution patterns. These biologically active indolobenzazocin-8-ones exhibited a cytotoxic potency, in particularly, indolobenzazocinone 2e which gave the activities in the nanomolar IC50 range. This study led to the delineation of structure activity relationship (SAR) relating substitution patterns of the indolobenzazocinone. We initially validated our hypothesis that the X-Cl species generated from the reaction between TMSCl and NXS could induce the halocyclization of N-methoxyalkynylimine to give the desired products in good to excellent yields. More reactions are being carried out with more substrates to demonstrate the generality of this method for the synthesis of 4-haloisoxazoles. The results will be reported in due course. แหล่งข้อมูล:
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