Closing Metathesis Strategy Research Articles

Synthetic Studies on Pyrroloindolizidine Skeleton Based on Gold–Catalyzed Hydroamination–Enamine Cyclization–Ring–Closing Metathesis Strategy

Synthetic Studies on Pyrroloindolizidine Skeleton Based on Gold–Catalyzed Hydroamination–Enamine Cyclization–Ring–Closing Metathesis Strategy

Novel methodology for the synthesis of the benz[a]anthracene skeleton of the angucyclines using a Suzuki-Miyaura/isomerization/ring closing metathesis strategy

The synthesis of the benz[a]anthracene skeleton of the angucyclines is described. Key steps involve the Suzuki-Miyaura reaction, isomerization of an aromatic allyl substituent to the corresponding styrene, and the use of the ring closing metathesis reaction to construct a benzene ring. For example, exposure of 3-allyl-2-bromo-1,4,5-trimethoxynaphthalene to (2-formyl-4-methoxyphenyl)boronic acid under palladium catalysis conditions resulted in the formation of 2-(3-allyl-1,4,5-trimethoxynaphthalen-2-yl)-5-methoxybenzaldehyde. This 2-naphthyl benzaldehyde then underwent a Wittig reaction to furnish 3-allyl-1,4,5-trimethoxy-2-(4-methoxy-2-vinylphenyl)naphthalene. Isomerization of the allyl group of this compound afforded the diene, (E)-1,4,5-trimethoxy-2-(4-methoxy-2-vinylphenyl)-3-(prop-1-en-1yl)naphthalene. Exposure of the formed diene to the Grubbs II catalyst resulted in the formation of the benzanthracene, 3,7,8,12-tetramethoxytetraphene, which was easily oxidized to the corresponding quinone.

A ring closing metathesis strategy for carbapyranosides of xylose and arabinose

The synthesis of β-carba-xylo and arabino pyranosides of cholestanol is described. The synthetic strategy, which is analogous to the Postema approach to C-glycosides, centers on the ring closing metathesis of an enol ether–alkene precursor to give a cyclic enol ether that is elaborated to a carba-pyranoside via hydroboration–oxidation on the olefin. The method, which is attractive for its modularity and stereoselectivity, may find wider applications to carba-hexopyranosides and other complex cycloalkyl ether frameworks.

A ring closing metathesis strategy for carbapyranosides of xylose and arabinose

The synthesis of β-carba-xylo and arabino pyranosides of cholestanol is described. The synthetic strategy, which is analogous to the Postema approach to C-glycosides, centers on the ring closing metathesis of an enol ether–alkene precursor to give a cyclic enol ether that is elaborated to a carba-pyranoside via hydroboration–oxidation on the olefin. The method, which is attractive for its modularity and stereoselectivity, may find wider applications to carba-hexopyranosides and other complex cycloalkyl ether frameworks.

Discovery of novel Cobactin-T based matrix metalloproteinase inhibitors via a ring closing metathesis strategy

The discovery of potent N-hydroxyl caprolactam matrix metalloproteinase (MMP) inhibitors (6) based on the natural product Cobactin-T (2) is described. The synthetic method, which utilizes the ring closing metathesis reaction, is compatible to provide complementary (R) and (S) enantiomers. These compounds tested against MMP-2 and 9, show that the R stereochemistry (i.e., 16), which is opposite for that found in the natural product Cobactin-T is >1000-fold more active with IC(50) values of 0.2-0.6nM against both enzymes. The variation in the incorporation of the sulfonamide enzyme recognition element (Ar(2)XAr(1)SO(2)N(R(1)), 6), along with alterations in the RCM/double bond chemistry (R(2)) provided a series of sub nanomolar MMP inhibitors. For example, compounds 16 and 34 were found to be the most potent with IC(50) values against MMP-2 and MMP-9 found to be between 0.2 and 0.6nM with 34 being the most potent compound discovered (MMP-2 IC(50)=0.39nM and MMP-9 IC(50)=0.22nM). Compounds 16 and 34 showed acceptable drug-like properties in vivo with compound 34 showing oral bioavailability.

ChemInform Abstract: Synthesis Staurosporines via a Ring Closing Metathesis Strategy as Potent JAK3 Inhibitors and Modulators of Allergic Responses.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthetic staurosporines via a ring closing metathesis strategy as potent JAK3 inhibitors and modulators of allergic responses

The synthesis and biological evaluation of JAK3 based staurosporine compounds is described. The compounds are constructed completely de novo, and a ring closing metathesis strategy is used to assemble the sugar mimetic portion. These analogs show potent JAK3 activity against isolated enzyme and in T-cells. One analog ( 32) showed unique biological effects during in vitro and in vivo tests including inhibition of STAT5 phosphorylation, blockade of mast cell responses, and reduction of JAK3 based effects in mice models of allergic disease.

Synthesis of indolizidines from dialkylated isocyanides: a novel radical cyclisation/N-alkylation/ring closing metathesis approach

Two dialkylated isocyanides were first synthesised from simple starting materials and then used as building blocks for the synthesis of indolizidines via a novel radical cyclisation/N-alkylation/ring closing metathesis strategy. Several functionalised indolizidines were accessed in good to excellent yields.

ChemInform Abstract: Synthesis of Benzofused Medium Ring Cyclic Ethers via a Michael Addition—Ring Closing Metathesis Strategy Involving Nitroaliphatic Compounds.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of benzo-fused medium ring cyclic ethers via a Michael addition–ring closing metathesis strategy involving nitroaliphatic compounds

Nitroalkenes derived from O-protected salicylaldehyde undergo facile Michael-type addition of nucleophiles possessing unsaturated tether. Ring closing metathesis of the Michael adducts provides benzo-fused medium ring cyclic ethers possessing a nitroalkyl functionality.

Synthesis of spirocyclic butenolides by ring closing metathesis

Spirocyclic butenolides were efficiently prepared by a ring closing metathesis strategy.

Stereoselective synthesis of advanced intermediates en route to Taxuspine U and X: a study of macrocyclization via ring closing metathesis to highly constrained twelve-membered rings

The stereoselective synthesis of an advanced intermediate of Taxuspine U and X has been accomplished using a ring closing metathesis strategy. The feasibility of ring closing metathesis in synthesizing highly constrained and functionalized macrocycles has been demonstrated provided the appropriate substrate structure and substitution pattern are chosen.

Studies towards the synthesis of the bicyclic 3,8-secotaxane diterpenoid system using a ring closing metathesis strategy

Molecular modelling studies on the interations between taxanes and tubulins, developed by us, revealed that modified Taxuspines U and X could adopt a conformation similar to that of the bioactive conformation of paclitaxel and could be well accommodated within the proposed model. Accordingly, simplified Taxuspine U and X analogues have been rationally designed and their bicyclic 3,8-secotaxane diterpenoids intermediates have been synthesized through an approach that involves ring closing metathesis (RCM) as the key step for the macrocycle formation. Extensive studies on RCM have been performed using chemically diverse substrates, outlining the influence in the macrocyclization of the presence and position of functionalities, the molecular constraints and the importance of the site of ring closure.

Synthesis of a Simplified Analogue of Eleutherobin via a Claisen Rearrangement and Ring Closing Metathesis Strategy.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of a simplified analogue of eleutherobin via a Claisen rearrangement and ring closing metathesis strategy

The enantioselective synthesis of a simplified eleutherobin analogue by ring closing metathesis (RCM) of the 2,9-divinyl-substituted tetrahydro-oxonin is described; the analogue and an advanced intermediate revealed microtubule stabilising properties in the micromolar range.

A new approach to functionalized spiropiperidines through tandem RCM and nitrogen-directed reactions.

The synthesis of a functionalized spiropiperidine via a tandem ring closing metathesis strategy is described, furthermore, the regio- and stereoselective functionalization of this compound has been achieved through a novel nitrogen-directed epoxidation reaction.

Formal total synthesis of (+)-trehazolin. Application of an asymmetric aldol-olefin metathesis approach to the synthesis of functionalized cyclopentenes.

An asymmetric synthesis of the aminocyclopentitol pseudosugar of trehazolin has been completed. The synthesis hinges on an asymmetric aldol-ring closing metathesis strategy to construct the five-membered ring with control of both the relative and absolute stereochemistry.