We have targeted a variety of prominent polyoxygenated natural products of the polyketide type, including lasonolide A, phorboxazoles, discodermolide, spongistatin, dictyoxetanes, mevinic acids and bryostatin. Advances in asymmetric intermolecular 4+3 cycloaddition methodology and other approaches have allowed us to prepare enantiopure oxabicyclic precursors. The polyketides are constructed by non-iterative, non-aldol methodology. Conventional electrophilic substitution including ipso substitution of 3-silylated and 3-stannylated furan has been suppressed in favour of the rapid 4+3 cycloaddition mode.
A further chapter has been added by the synthesis of glycosides and pseudo-C-glycosides. These glycosides are synthesized de novo. Similar to the polyketides the glycosides are prepared from just a handful of easily obtainable key precursors.
Radical reactions involving acetylenes as radical acceptors, 6-endo-digonal cyclisations and heterocyclic chemistry have been studied and applied. Precursors are 1,5-enynes, and reactive vinyl radical intermediates have been tamed and captured regio- and stereoselectively with formation of complex oxacyclic frameworks.
Another area is the chemistry of Cinchona alkaloids. We have recently invented a transformation of quinine and quinidine into Quincorine and Quincoridine, respectively. These bicyclic aminoalcohols are enantiopure and new and of much interest in various fields of chemistry and in interdisciplinary studies of pharmacology and asymmetric synthesis. A summary of this work has recently appeared (ref. 271).
Other recent work is concerned with the total synthesis of the disorazoles (ref. 261, 266, 267).