Catalytic Selective Cyclizations of Aminocyclopropanes: Formal Synthesis of Aspidospermidine and Total Synthesis of Goniomitine

Abstract

Sanfte Kontrolle: Je nach Reaktionsbedingungen gelingt die Titelreaktion an der N1‐ oder der C3‐Position eines Indolrings (siehe Schema). Das neben Aspidospermidin mithilfe dieser Strategie synthetisierte Goniomitin ist gegen mehrere Tumorzelllinien cytotoxisch (IC50=150–400 nM). Cbz=Benzyloxycarbonyl, Ts=4‐Toluolsulfonyl.

Ring-opening, cycloaddition and rearrangement reactions of nitrogen-substituted cyclopropane derivatives

“…Examples are displayed in Table 10. 170,201,202,205,206 Analysis of the results suggests that monocyclic cyclopropane substrates perform less effectively in these reactions than fused bicyclic compounds (entry 5 vs entry 1, entry 6 vs entry 3 and entry 8 vs entry 7). As already pointed out in the previous subsection, cyclisations onto unprotected indole rings may occur either at C3 or at N1.…”

“…For instance, the secondary amine tetracycle obtained after deprotection of the N-Cbz group of the product 126 is a known precursor of the alkaloid aspidospermidine. 170,201,202 The total syntheses of (±)-deethyleburnamonine (Scheme 83) 206 and of the cytotoxic alkaloid jerantinine E (Scheme 84) 207 are based on the same strategy. Scheme 86.…”

“…Acid-catalysed ring-opening of aminocyclopropanes and intramolecular trapping with indole moieties 170,201,202. With substrates in which the nitrogen atom attached to the cyclopropane moiety is not embedded in a ring, only few related transformations are described.…”

Esf-Cost High-Level Research Conference Natural Products Chemistry, Biology and Medicine III

“…Isolated in 2003 from a marine tunicate Aplidium haouarianum off the coast of Spain, haouamine A was reported to have high activity against HT-29 human colon-cancer cells (IC 50 = 0.1 µg/ml). This unprecedented polyphenolic alkaloid contains a 3-aza- [7]-paracyclophane macrocycle that is so strained that the cyclophane arene is bent out of planarity and exists in a boat-like conformation. Burns synthesized this challenging target in only eight steps from a readily available indanone precursor.…”

“…Chair: Bruno Botta (University "La Sapienza," IT) Jérôme Waser (Ecole Polytechnique Fédérale de Lausanne, Switzerland) discussed the total synthesis of goniomitine (13) and indole alkaloid from the tree Gonioma Malagasy, using a donor-acceptor cyclopropane strategy (figure 7) [7]. A donor-acceptor cyclopropane is one that contains an electron-donating substituent and an electron-withdrawing substituent.…”