Tremorgenic Indole Alkaloids. The Total Synthesis of (−)-Penitrem D

Abstract

A convergent, stereocontrolled total synthesis of the architecturally complex tremorgenic indole alkaloid (-)-penitrem D (4) has been achieved. Highlights of the synthesis include an efficient, asymmetric synthesis of the western hemisphere; the stereocontrolled assembly of the I-ring; discovery of a novel autoxidation to introduce the C(22) tertiary hydroxyl group, required for tremorgenic activity; union of fully elaborated eastern and western hemispheres, exploiting an indole synthetic protocol developed expressly for this purpose; and a late-stage, stereoselective construction of the A and F rings exploiting a Sc(OTf)(3-)promoted reaction cascade. The longest linear sequence leading to (-)-penitrem D (4) was 43 steps.

Iron salt, a cheap, highly efficient and environment-friendly metal catalyst for Se–Se bond cleavage and the further reaction with methylenecyclopropanes under mild conditions

“…Therefore, they are useful building blocks in organic synthesis. During the past decade, the applications of MCPs had been well investigated and a series of interesting organic skeletons could be easily constructed from MCPs, which include homoallylic compounds [ Four-membered carbon ring structures are widely present in natural products [26,27]. They are also valuable in organic synthesis [28].…”

Functionalized organolithium compounds in total synthesis

“…Thus, N-silylated aniline 220 has been treated with 2.2 equiv of secbutyllithium to provide the organolithium reagent 221 which reacted with lactone 222 giving rise to intermediate 223 capable of an intramolecular Peterson olefination to furnish indole 224 after silica gel treatment, which supplied the BCDE-ring system in a recent total synthesis of tremorgenic indole alkaloid (K)-penitrem D (225), a component of the ergot fungi family of alkaloids (Scheme 37). 99 Another example of the use of a benzyllithium, but which is Benzyllithium 233 bearing a lithium carboxylate at the g-position has been obtained by LDA-promoted deprotonation of the corresponding carboxylic acid 232, being used as nucleophile in the reaction with chiral allylic bromide 234 (Scheme 39). The resulting acid 235 was used as an intermediate in the synthesis of some b-resorcylic acid derivatives 236 isolated from Lasiodiplodia theobromae and with potato microtuber-inducing activity.…”

Rhizovarins A–F, Indole-Diterpenes from the Mangrove-Derived Endophytic Fungus Mucor irregularis QEN-189

“…Indolediterpenes are a group of structurally interesting mycotoxins that have mainly been characterized from Aspergillus and Penicillium species, 11−15 have been reported to possess significant antiinsectan activity, 13,14 and have attracted great interest from synthetic chemists as well. 16 Recent research shows they are novel inhibitors of the Wnt/β-catenin pathway in breast cancer cells. 17 This paper describes the details of fungal isolation, genome mining of the biosynthetic clusters, and isolation and structure elucidation of the novel indole-diterpenes, as well as their inhibitory activity against the HL-60 and A549 tumor cell lines.…”