Natural Products Containing Medium‐Sized Nitrogen Heterocycles Synthesized by Ring‐Closing Alkene Metathesis

Abstract

The formation of carbon-carbon bonds is a crucial issue in organic synthesis. Out of all methodologies available, the metathesis reaction has, over the past decade, evolved as one of the most useful tools in this field to rapidly construct the skeleton of carba-and heterocyclic molecules [1]. Key step of the metathesis reaction entails the metal-catalyzed redistribution of two carbon-carbon double bonds by a scission-recombination process [2]. Among various applications of the metathesis reaction, ring-closing metathesis (RCM) has emerged as one of the most powerful tools for the construction of natural and unnatural cyclic compounds (Scheme 2.1) [3]. Other types of metathesis reactions developed so far include cross-metathesis (CM), ring-opening metathesis (ROM), ring rearrangement metathesis (RRM, combining ROM with RCM in a tandem sequence), and ene-yne metathesis [3].The metathesis reaction has already been used for several decades in polymer chemistry for ring-opening metathesis polymerization (ROMP) [4]. Only since the development of well-defined molybdenum and ruthenium carbene complexes by Schrock [5] and Grubbs [6] in 1990 and 1992, respectively, an explosion of their application in organic synthesis has been witnessed. Initially, it was demonstrated that the Schrock catalyst [Mo]-I could serve as a homogeneous catalyst for olefin RCM [7]. Unfortunately, metal carbene complex [Mo]-

2-Amino-1,3,4-thiadiazoles as prospective agents in trypanosomiasis and other parasitoses

“…Nitrogen-containing heterocycles are found in a wide range of natural products and biologically active synthetic compounds (8)(9)(10)(11)(12)(13)(14)(15). In addition, nitrogen-containing heterocycles constitute a common structural unit of many marketed drugs (16,17).…”

“…Effective drugs should be able to treat both stages of the disease or at least one of them. Pentamidine (9) and suramin (10) are used in early stages of African trypanosomiasis, whereas eflornithine (12) or the combination nifurtimox (13)-eflornithine (12) is approved for second-stage treatment. Melarsoprol (11), an arsenical drug with high toxicity, is also approved in later stages ( Fig.…”

Sequential Two‐Fold Claisen Rearrangement, One‐Pot Ring‐Closing Metathesis and Cross‐Metathesis as a Route to Substituted Benzo[b]azepine‐2‐one, Benzo[b]azepine and Benzo[b]oxepine Derivatives

“…[2 -6] Recent progress in various metal-catalyzed ring-forming reactions has facilitated access to these classically otherwise difficult-to-make ring systems. [7][8][9][10][11][12][13][14] In particular, olefin-metathesis mediated transformations, [15][16][17][18][19][20][21][22][23][24][25][26][27][28] either in tandem or in sequence with other named and unnamed reactions, [29,30] have provided rapid access to several structurally embellished entities accommodating the core ring systems. However, comparatively less attention has been paid to develop synthetic methodologies that simultaneously address incorporation of functionalities within the core ring system.…”

Synthesis of Tetracyclic Molecules Containing Medium-Sized Heterocycles: Scope Expansion of Cascade Nicholas and Pauson–Khand Methodology

“…2 Their structurally unfavorable conformational states brought about by entropic and enthalpic effects, means that their synthesis primarily relies on ring-closing metathesis reactions. 3 Although the number of synthetic examples of eight-membered heterocycles has increased in natural product synthesis, that of nine-membered rings, especially those with multiple heteroatoms within the ring framework, is limited. 1, 3 Recently, we reported a synthetic route towards tetracyclic compounds containing a nine-membered sultam, wherein we demonstrated that a cobalt-alkyne complex-mediated cyclization could serve as a powerful approach for the synthesis of nine-membered heterocycles containing nitrogen and sulfur atoms.…”

“…3 Although the number of synthetic examples of eight-membered heterocycles has increased in natural product synthesis, that of nine-membered rings, especially those with multiple heteroatoms within the ring framework, is limited. 1, 3 Recently, we reported a synthetic route towards tetracyclic compounds containing a nine-membered sultam, wherein we demonstrated that a cobalt-alkyne complex-mediated cyclization could serve as a powerful approach for the synthesis of nine-membered heterocycles containing nitrogen and sulfur atoms. 4 Motivated by the rapid construction of novel nine-membered ring frame-works, we attempted to clarify the substrate scope and limitations by modifying the ring size and constituent elements.…”