| The diastereoselective total syntheses of the unnatural (+)-enantiomer of the alkaloid ({dollar}-{dollar})-debromoflustramine B, isolated from the marine bryozoan Flustra foliacea (L), and that of the unnatural (+)-enantiomer of the alkaloid (-)-pseudophrynaminol, isolated from the skin of the Australian frog Pseudophryne coriacea, from the cyclic tautomer of L-tryptophan are described. The syntheses were achieved by the development of two key reactions namely, functionalization at C-3a by free radical benzylic bromination and formation of the all important quaternary carbon-carbon bond via a free radical mediated allylation reaction. The optical rotations and CD spectra of the two alkaloids synthesized are opposite in sign to those of the natural materials, thus enabling the absolute configuration of the natural products to be established as 3aS, 8aR.; A system was developed wherein asymmetric induction in radical cyclizations was achieved by the use of 1,3-dioxan-2-yl radicals as chiral acyl radical equivalents. Extensive experimentation with 1,3-dioxan-2-yl radicals generated from C2 symmetric acetals resulted in modest diastereoselectivity. The design, synthesis and application of disymmetrically substituted trans-1,3-dioxabicyclo (4.4.0) decanes was achieved successfully. Finally, 10,10-dimethylbornane-2-exo, 10-diol was specifically designed and prepared in optically pure form. The cyclizations resulting from the corresponding acetals proceeded with excellent diastereoselectivity. The cyclized products after hydrolysis yielded highly enantiomerically enriched cyclopentanones. |
