TOTAL SYNTHESIS OF PUREALIN AND ITS ANALOGUESSYNTHESIS OF LAGUNAPYRONE B AND ITS ISOMERS WITH FLUOROUS MIXTURE SYNTHESIS

摘要

Purealin is a natural product that has been isolated from the sea sponge Psammaplysilla purea known to inhibit axonemal dynein. A total synthesis of purealin and a small library of purealin analogues are reported here in. This research allows initial examination of biological properties of purealin and its analogues. The results indicate purealin and some of the analogues inhibited the ATPase activity of isolated cytoplasmic dynein heavy chain. The inhibitory effect of purealin was concentration-dependent. The library of puealidin A showed effective antiproliferative activity against a mouse leukemia cell line, but selective activities against human carcinoma cell lines. These data illustrate small molecule inhibitors of cytoplasmic dynein that could prove to be useful tools for investigation of the cellular function of cytoplasmic dynein.Lagunapyrone B, a marine bacteria isolated by Fenical in 1996, possesses an unusual alpha-pyrone functionalized with highly methyl-branched side chain, a conjugated diene and two skipped dienes. The carbon skeleton of lagunapyrones has not been previously observed. Because of the long distance between the two groups of stereocenters, the absolute configuration of these compounds is difficult to assign using spectroscopic methods. Using fluorous mixture synthesis (FMS), we have synthesized four diastereomers in order to determine the absolute configuration of the natural product. By comparing the [¦Á]D25 data of final four isomers, compound 2.1c was determined to be the natural product, whose configuration is 6R, 7S, 19S, 20S, 21R.