Grant-funded Project Nr. 385/2004/B-CH/FaF Final Report
Project title:
Continuation of Synthetic Studies on Furanones Derived from Uncinine
Research leader:
Mgr. Helena Fáková, 2001
Co-researcher:
Doc. RNDr. Milan Pour, Ph.D.;
Jitka Sedláková
Period of project:
2004-2004
Overall grant:
87 000 CZK
Project Results
The project was directed towards the preparation of uncinine, which is one of the alkaloids isolated from the plant Artabotrys uncinatus. The possibility that the compound would possess interesting biological properties was the main reason, why we initiated synthetic studies, which should result in the total synthesis of uncinine as well as its analogues. The total synthesis would also confirm the structure of the substance, which was derived only on the basis of the spectral data.
Our proposed synthesis of uncinine, based on Pd-catalyzed carbonylation of a suitable precursor as the key step, has been successfully accomplished. All spectral charakteristics (NMR, IR, HREIMS) of our synthetic substance were in excellent agreement with those published for the natural product. The first total synthesis of uncinine commences with a simple, commercially available starting material and involves eight synthetic steps. We assume that after the optimization of the final step, the sequence will enable us to provide an economic supply of uncinine for extensive pharmacological evaluation.
In the synthesis of uncinine, the desired γ-alkylidene butenolide, disubstituted at the exocyclic terminus of the double bond, was constructed by a tandem Pd-catalyzed carbonylative lactonization of a ß-iodoenone precursor in a single step. Considering the mild conditions of this process (1 atm CO), further progress in the development of carbonylative lactonizations involving carbonyl oxygen as an internal nucleophile has been made. Two analogues of uncinine, which will also be tested for their cytotoxic and antifungal activities, were prepared, as well.