Stereoselective Synthesis of (+)-11βH,13-Dihydroestafiatin, (+)-11βH,13-Dihydroludartin, (−)-Compressanolide, and (−)-11βH,13-Dihydromicheliolide from Santonin

Abstract

Starting from 2 and 3, obtained from santonin (1), we have synthesized natural guaianolides 4-7. Chemoselective epoxidation of 2 gave (+)-11betaH,13-dihydroestafiatin (4), and epoxidation of 3 followed by regioselective elimination of the hydroxyl group afforded (+)-11betaH,13-dihydroludartin (5). Sharpless' mild regioselective ring-opening of 4 and 5 followed by hydrogenolysis yielded (-)-compressanolide (6) and (-)-11betaH,13-dihydromicheliolide (7), respectively.

Concise Total Synthesis of (−)-8-Epigrosheimin

“…Many of them display a broad biological profile including strong antitumor, antihelmitic, contraceptive, plant growth-regulatory, antiinflammatory, and cytostatic properties, which makes them interesting lead structures for new drugs. While many synthetic approaches have therefore been developed, there are still some challenges in synthesizing this kind of natural lactone. One of them is the efficient assembly of the trans -fused γ-butyrolactone ring.…”

Synthesis of Biologically Active Guaianolides with a trans‐Annulated Lactone Moiety

“…A further strategy using (-)-α-santonin (125) as a starting point was extensively used by the groups of Ando [24,53] and Pedro [54] to access several natural products of the guaianolide family (Scheme 27). The transformation of the 6,6-into the 5,7-ring system is accomplished by a carbocation rearrangement initiated by the solvolysis of 140.…”

Natural sesquiterpenoids

“…Santonin has been used as the starting material for the synthesis of (ϩ)-11βH,13-dihydroestafiatin, (ϩ)-11βH,13-dihydroludartin, (Ϫ)-compressanolide and (Ϫ)-11βH,13-dihydromicheliolide. 353 Progress in the study of the sesquiterpene lactones isolated from the genus Xanthium has been reviewed. 354 The xanthanolide 353 has been obtained from the flowers of Paulownia coreana.…”