Total synthesis of spongistatin 1: a synthetic strategy exploiting its latent pseudo-symmetry.
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Biological Factors↗
Biomedical subjects
Steven V Ley
Publications and source records attributed to Steven V Ley.
A phase-switch purification approach for the expedient removal of tagged reagents and scavengers following their application in organic synthesis.
In this paper we wish to report on a variety of expedient chemical transformations and purifications achieved via a generic "catch and release" methodology, based on a synthetically inert bipyridyl chelating tag that can be selectively captured with a resin-bound copper(II) species. Utilising this approach we are able to derive many of the same benefits associated with both solid phase synthesis and supported reagent methods.
2,2'-Dipyridyl↗
The use of a continuous flow-reactor employing a mixed hydrogen-liquid flow stream for the efficient reduction of imines to amines.
Imines have been reduced to amines in high yield, and with excellent chemoselectivity, by catalytic hydrogenation in a continuous flow-reactor, utilising an electrochemically-generated hydrogen source to produce a mixed hydrogen-liquid flow stream.
Amines↗
Total synthesis of antascomicin B.
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Molecular Structure↗
Efficient batch and continuous flow Suzuki cross-coupling reactions under mild conditions, catalysed by polyurea-encapsulated palladium (II) acetate and tetra-n-butylammonium salts.
Suzuki cross-coupling reactions are effected in both conventional organic solvents, under continuous flow conditions at 70 degree C, and in batch mode in supercritical carbon dioxide (scCO2), at temperatures as low as 40 degrees C in the presence of palladium(II) acetate microencapsulated in polyurea [PdEnCat] and tetra-n-butylammonium salts.
Acetates↗
The total synthesis of the annonaceous acetogenin 10-hydroxyasimicin.
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Annonaceae↗
Total synthesis of the Fusarium toxin equisetin.
A short stereoselective synthesis of the Fusarium toxin equisetin, a potent inhibitor of HIV-1 integrase enzyme is described, using as the key step a stereoselective intramolecular Diels-Alder reaction of a fully conjugated E,E,E-triene with a trisubstituted gamma,delta-unsaturated beta-ketothioester.
Fusarium↗
Organocatalysis with proline derivatives: improved catalysts for the asymmetric Mannich, nitro-Michael and aldol reactions.
Tetrazole and acylsulfonamide organocatalysts derived from proline have been synthesised and applied to the asymmetric Mannich, nitro-Michael and aldol reactions to give results that are superior to the proline-catalysed counterpart.
Catalysis↗
Preparation of enantiopure butane-2,3-diacetals of glycolic acid and alkylation reactions leading to alpha-hydroxyacid and amide derivatives.
The preparation of butane-2,3-diacetal protected glycolic acid and related systems is described together with highly selective alkylation reactions of (R,R) and (S,S) butanediacetal protected glycolic acid. These compounds are readily deprotected to give enantiopure alpha-hydroxyacids, alpha-hydroxyesters or alpha-hydroxyamides by suitable choice of conditions.
Acetals↗
Studies on the generation of enolate anions from butane-2,3-diacetal protected glycolic acid derivatives and subsequent highly diastereoselective coupling reactions with aldehydes and acid chlorides.
Highly diastereoselective coupling reactions of enolates derived from butane-2,3-diacetal protected glycolic acids 1 and 2 and their alkylated derivatives with aldehydes are reported together with their efficient acid-catalysed deprotection to yield enantiopure anti-2,3-dihydroxyesters. A procedure to provide the corresponding syn-2,3-dihydroxyesters is also described in two cases, proceeding via an acylation-reduction sequence. An usual double addition reaction of butane-2,3-diacetal protected glycolic acid to small aliphatic acid chlorides provides a synthetically useful, densely-functionalised lactone after acidic deprotection.
Acetals↗
Enantioselective organocatalytic cyclopropanation via ammonium ylides.
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Journal Article↗
A concise total synthesis of (+)-okaramine C.
The first total synthesis of (+)-okaramine C is described. Our previously described selenocyclisation-oxidative deselenation sequence was used to establish a 3a-hydroxy-pyrrolo[2,3-b]indole core, which was modified by selective epimerisation to the common pyrrolo[2,3-b]indole of the okaramines.
Indole Alkaloids↗
5-Pyrrolidin-2-yltetrazole as an asymmetric organocatalyst for the addition of ketones to nitro-olefins.
The organocatalytic Michael addition of enamines derived from ketones to a range of nitro-olefins has been effected using the l-proline derived 5-pyrrolidin-2-yltetrazole.
Journal Article↗
Synthesis of the thapsigargins.
The thapsigargins are a family of complex guaianolides with potent and selective Ca(2+)-modulating properties. This article documents the evolution of a synthetic route through several iterations to a final practical and scaleable synthetic route capable of generating both unnatural and natural products based around the guaianolide skeleton.
Apiaceae↗
Multi-step application of immobilized reagents and scavengers: a total synthesis of epothilone C.
The total synthesis of the cytotoxic antitumour natural product epothilone C has provided a stage for the exploitation and further development of immobilized reagent methods. A stereoselective convergent synthetic strategy was applied, incorporating polymer-supported reagents, catalysts, scavengers and catch-and-release techniques to avoid frequent aqueous work-up and chromatographic purification.
Antineoplastic Agents↗
Anomeric oxygen to carbon rearrangements of alkynyl tributylstannane derivatives of furanyl (gamma)- and pyranyl (delta)-lactols.
Tetrahydropyran and tetrahydrofuran containing natural products, drugs and agrochemicals often possess carbon-carbon bonds adjacent to the heteroatom. Consequently, new methods for the construction of anomeric carbon-carbon bonds are of considerable importance. We have devised a new strategy to access these systems that requires the treatment of O-glycoside alkynyl tributylstannane derivatives of furanyl and pyranyl lactols with Lewis acid to effect oxygen to carbon rearrangements. This leads to the formation of the corresponding carbon linked alkynol products that can be further manipulated to produce key structural motifs and building blocks for the assembly of complex molecules.
Alkynes↗
Polymer-assisted, multi-step solution phase synthesis and biological screening of histone deacetylase inhibitors.
The polymer-assisted solution phase synthesis (PASP) of an array of histone deacetylase (HDAc) inhibitors is described. HDAc inhibitors have considerable potential as new anti-proliferative agents. Selected compounds were shown to inhibit both human endothelial cell proliferation, and the formation of tubules (neovascularisation) in an in vitro model of angiogenesis.
Cell Proliferation↗
Microwave assisted Leimgruber-Batcho reaction for the preparation of indoles, azaindoles and pyrroylquinolines.
The development of enhanced conditions for Lewis acid catalysed Leimgruber-Batcho indole synthesis using microwave acceleration is described. This approach has permitted the preparation of a variety of heteroaromatic enamine intermediates in good yield and high purities. Subsequent catalytic hydrogenation reactions, under various conditions including the use of a solid-phase encapsulated catalyst, furnish the corresponding indole derivatives in good yields.
Journal Article↗