Synthesis of simplified analogues of eleutherobin via a Claisen rearrangement/RCM strategy

The enantioselective synthesis of a number of simplified analogues of the cytotoxic natural product eleutherobin is reported.     

Synthesis of phosphorus containing medium ring heterocycles by sequential Claisen rearrangement and ring closing metathesis

An efficient method for the synthesis of novel medium ring phosphorus containing heterocycles starting from phenol derivatives by ruthenium catalyzed ring closing metathesis is described. This work deals with a sequential aromatic Claisen-rearrangement, coupling of an allyl/vinyl phosphonate, and ring closing metathesis reaction. All of these reactions were carried out at ambient temperature to afford the medium-sized phosphorus heterocycles in excellent yields.     

Synthesis of novel simplified sarcodictyin/eleutherobin analogs with potent microtubule-stabilizing activity, using ring closing metathesis as the key-step

The synthesis of a number of novel simplified eleutheside analogs with potent tubulin-assembling and microtubule-stabilizing properties is described, using ring closing metathesis as the key-step for obtaining the 6-10 fused bicyclic ring system. The RCM precursors were synthesized starting from aldehyde 3 [prepared in 6 steps on a multigram scale from R-(−)-carvone in 30% overall yield] via multiple stereoselective Brown allylations. Second generation RCM catalyst 13 gave the desired ring closed 10-membered carbocycles as single Z stereoisomers in good yields. The RCM stereochemical course (100% Z) likely reflects thermodynamic control. The crucial role of the protecting groups of the homoallylic and allylic substituents for the efficiency of the RCM reactions is discussed. These simplified analogs of the natural product (lacking inter alia the C-4/C-7 ether bridge) retain potent microtubule-stabilizing activity. However, the cytotoxicity tests did not parallel the potent tubulin-assembling and microtubule-stabilizing properties: limited cytotoxicity was observed against three common tumor cell lines (human ovarian carcinoma and human colon carcinoma cell lines, IC₅₀ in the μM range given in Table 2), three orders of magnitude less than paclitaxel (IC₅₀ in the nM range).     

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 cholaphanes by ring closing metathesis

The synthesis of cholaphanes by ring closing metathesis (RCM) of 3α,7α,12α,24-tetraol allyl derivatives, obtained from cholic acid, was attempted. The reactions of tetraol 3,24-diallyl ether or 3,24-diacrylate were not satisfactory. However, diallyl derivatives of disteroidal 3,3′- or 24,24′-ortho-phthalates reacted smoothly affording cyclic dimers in good yields. In all the reactions studied, the E isomers of the macrocycles were obtained in excess.     

Synthesis of huperzine B through ring closing metathesis

Huperzine B and its analogues were obtained through ring closing metathesis of N-alkenyl amine to the corresponding tricyclic compounds.     

A new approach to A/B ring analogue of eleutherobin and sarcodictyns through a sequence of highly diastereofaceselective Diels-Alder reaction and ring opening-ring closing metathesis (RO-RCM)

An approach to the construction of A/B ring analogue of antitumour compounds eleutherobin and sarcodictyns is described. The key steps involve a highly diastereofaceselective Diels-Alder reaction of a dienophile containing a furanosugar moiety with cyclopentadiene and ring opening-ring closing metathesis of the resulting adduct.     

Synthesis of spirocyclic butenolides by ring closing metathesis

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

Synthesis of bruguierol A employing ring closing metathesis

An expedient synthesis of bruguierol A encompassing a novel 2,3-benzo-8-oxabicyclo[3.2.1]octane ring system is described employing ring closing metathesis to generate the oxa-bridged tricyclic core.     

Studies toward Taxuspine X, a potent multidrug-resistance reversing agent, via ring closing metathesis strategy

The synthesis of bicyclic 3,8-secotaxane diterpenoids, which includes Taxuspine U and X, has been achieved through an approach that involves a ring closing metathesis reaction as key step for the macrocycle formation.     

Synthesis of vinylcyclopropanes by allylation/ring-closing metathesis/Claisen rearrangement

A facile double allylation/ring-closing metathesis/Claisen rearrangement route for preparing vinylcyclopropanes 6 is developed. The efficient synthesis includes O-allylation of α-allyl-α-sulfonylketones 8 with allylic bromides, ring-closing metathesis of diallyl compounds 9 and sequential Claisen rearrangement of the resulting oxepines.     

Synthesis of cycloalkenyl geminal bisphosphonates by ring closing metathesis

Five‐ and six‐membered cycloalkenyl bisphosphonates were obtained by ring closing metathesis (RCM) reactions of diethyl bis(alkenyl)methylene bisphosphonates using ruthenium alkylidene catalysts. The substitution pattern on the double bonds involved in the reaction greatly influences the reaction rate. The synthesis of the starting materials was carried out by dialkylation of tetraethyl methylene bisphosphonate or through a Michael addition of Grignard reagents to tetraethyl vinylidene bisphosphonate followed by alkylation, depending on the structure of the required substrate. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:332–338, 2010; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20622     

A synergistic approach to polycyclics via a strategic utilization of Claisen rearrangement and olefin metathesis

Olefin metathesis promoted by a well-defined metal carbene complex has evolved into an efficient method for the construction of a broad range of carbocyclic and heterocyclic rings of varying size. The synthetic potential of the olefin metathesis has been further increased by combining various other C-C bond forming processes either in tandem or in sequence. Herein, application of Claisen rearrangement and olefin metathesis to prepare various intricate and/or biologically important targets has been described.     

Synthesis of sulphur-containing heterocycles by ring closing diene metathesis

We have shown that, surprisingly, the Schrock molybdenum alkylidene catalyst 1 can perform ring closing metathesis reactions on substrates containing a sulphide group, converting diallyl sulphide 5 to 2,5-dihydrothiophene 6 with >99 % conversion. By contrast, the ruthenium alkylidene catalyst 2, which is generally more tolerant of functional groups in the substrate, is unreactive towards diallylsulphide. However even the molybdenum catalyst 1 proved unable to catalyse ring closure of tetrathiafulvalene derivative 7.     

Synthesis of small cyclic peptides via reverse turn induced ring closing metathesis of tripeptides

A reverse turn induced (gamma/beta-turn) cyclization of tripeptides 1 can be performed in a ring closing metathesis reaction with Grubbs' catalyst to the corresponding cyclic peptides 2. These cyclic peptides may be useful probes as a conformationally constrained mimic of the bioactive conformation of structurally related HIV protease inhibitors.     

Synthesis of fused dihydropyrido[e]purines via ring closing metathesis

Ring closing metathesis (RCM) of 8,9-diallylpurines or 9-butenyl-8-vinylpurines with the Grubbs 2nd generation catalyst resulted in fused 6,9- or 8,9-dihydropyrido[e]purines, respectively. The 8,9-dialkenylpurines were prepared from 8-bromopurines after 9-alkenylation and subsequent Stille coupling at C-8 with alkenylstannanes in the presence of Pd(PPh₃)₄ or Pd(PPh₃)₂Cl₂.     

Diversity-oriented approach to cyclophanes via Claisen rearrangement and ring-closing metathesis as key steps

Among numerous reactions to prepare cyclophane derivatives, Claisen rearrangement reaction is very useful. We have prepared cyclophanes containing ethylene oxy bridge by double Claisen rearrangement reaction and ring-closing metathesis reaction as key steps.     

Synthesis of novel aromatic macrolactones via ring closing metathesis of substituted phenylalkanoic acid allylic esters

Stable aromatic macrolactones have been synthesized and characterized from 2‐ and 3‐substituted phenylalkanoic acid systems in modest yields.     

Synthesis of an eight-membered cyclic pseudo-dipeptide using ring closing metathesis

Ring closing metathesis of diallylglycine 6 provided cyclic Z-olefin 7 in 80% yield. The reaction was promoted by substitution of the amide nitrogen with the 2,4-dimethoxybenzyl group allowing for the required cis diallylglycine amide rotamer. Removal of the protecting groups provided cyclic dipeptide 2, a constrained scaffold useful in peptidomimetic research.     

A ring-closing metathesis approach to a synthesis of the B ring of eleutherobin

A short and efficient RCM route is reported for the construction of the key nine-membered B ring of eleutherobin starting from the readily available 1,2,5,6-diisopropylidene-d-glucose.