ChemInform Abstract: A NEW TOTAL SYNTHESIS OF DL‐PUMILIOTOXIN C VIA AN INDANONE

Abstract

~~~~Summary dl-Pumiliotoxin-C (4) was synthesized in a practical manner from trans-4-hexenal (9). The key step 14+15 (Scheme 3) involves an intramolecular Dielv-Alder reaction giving mainly the ciy-fused indanols 15a, which were converted to the cis-fused kctone 16. After Beckmann-rearrangement of 16 the octahydroquinolinone 7 was transfoimed to the lactim-ether 23. (Scheme 7). Reaction of 23 with propylmagnesium bromide followed by hydrogenation furnished dl-4 in a highly stereoselective fashion. . The complex stereochemical features 2, and the paucity of this physiologically active alkaloid provide a considerable challenge to the synthetic chemist [3-61. We have recently met this challenge by using the intramolecular Diels-Alder reaction 2 + 3 as the crucial step in the synthesis outlined below3) (Scheme 1 ) ; one of its key features is that during the conversion of 1 to 4 the original chiral center of the amine 1 controls to a major extent the configuration of the other chiral centers which are formed simultaneously in the cycloaddition process.We now wish to report an alternative synthetic scheme (5 i 6 i 7 --f 4) following a different stereochemical strategy in which center C(2) is induced by the other three chiral centers*) during the transformation 7 i 4; for their assembly an intramolecular cycloaddition 5 + 6 was envisaged. Since both trans-dienes 5a, as well as the corresponding cis-dienes (5b) may be considered as leading selectively to the required cis-junction of 6 the two isomeric trienols 11 and 12 were separately prepared from the dienynol 10 in a stereocontrolled manner.