Herein we describe the total synthesis of five guaianolide natural products: thapsigargin, thapsivillosin C, thapsivillosin F, trilobolide and nortrilobolide. Prodrug derivatives of thapsigargin have shown selective in vivo cytotoxicity against prostate tumours and the need for further investigation of this phenomenon highlights the importance of these total syntheses. The first absolute stereochemical assignment of thapsivillosin C is also delineated.

1,3-dipolar cycloaddition reactions of nitrones with alkenes and alkynes are well-studied reactions in solution-phase organic chemistry. However, the number of studies concerned with their application in solid-phase organic synthesis is rather low compared to other 1,3-dipoles, e.g. azides or nitrile oxides. This tutorial review aims to summarise the main approaches towards the application of nitrones in 1,3-dipolar cycloaddition reactions on solid supports in addition to subsequent transformations with polymer-bound isoxazolidines and reactions using polymer-bound catalysts.

The enantioselective total synthesis of thapsigargin, a potent, selective inhibitor of the Ca2+ pump SERCA, is described. Starting from ketoalcohol 8, key steps involve regioselective introduction of the internal olefin at C4-C5, judicious protecting group choice to allow chelation-controlled reduction at C3, and chemoselective introduction of the angelate ester function at C3-O. A selective esterification approach completes the total synthesis in a total of 42 steps and 0.61% overall yield (88.6% average yield per step). [reaction: see text].

Terpenes U 0200 Total Synthesis of Thapsigargin, a Potent SERCA Pump Inhibitor. -(BALL, M.; ANDREWS, S. P.; WIERSCHEM, F.; CLEATOR, E.; SMITH, M. D.; LEY*, S. V.; Org. Lett. 9 (2007) 4, 663-666; Dep. Chem., Univ. Cambridge, Cambridge CB2 1EW, UK; Eng.) -R. Steudel 27-154

Keywords: Solid-phase synthesis / Isoxazoli(di)nes / Piperazin-2-one scaffolds / Cycloaddition / NϪO-bond cleavageIsoxazolidines and 1,3-aminoalcohols with a piperazin-2-one skeleton were readily prepared on a solid support through [3+2] cycloaddition and subsequent N−O-bond cleavage, starting from a polymer-supported cyclic nitrone. Libraries of functionalized 1,3-aminoalcohols and their derivatives were obtained by automated amine acylation and Mitsunobu reac-