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Margaret A. Brimble - One of the best experts on this subject based on the ideXlab platform.
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Benzannulated Spiroketal natural products: isolation, biological activity, biosynthesis, and total synthesis
Organic & biomolecular chemistry, 2019Co-Authors: Rachel M. Gillard, Margaret A. BrimbleAbstract:The Spiroketal moiety is an important privileged scaffold that occurs extensively in natural products, drugs, and bioactive molecules. Naturally occurring Spiroketals are numerous, however aryl-fused Spiroketals are relatively rare. The only comprehensive review disclosing the isolation, biological activity, and synthesis of benzannulated Spiroketal natural products was published nearly a decade ago. This review will serve as an update of the 2009 review and include all known families of benzannulated Spiroketals, detailing their isolation and biological activity where relevant. Although not exhaustive, endeavours towards their total synthesis will be discussed.
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Enantioselective access to benzannulated Spiroketals using a chiral sulfoxide auxiliary.
Organic & biomolecular chemistry, 2013Co-Authors: Harry R. M. Aitken, Jonathan G. Hubert, Daniel P. Furkert, James M. Wood, Margaret A. BrimbleAbstract:This article describes our efforts to develop an asymmetric synthesis of bisbenzannulated Spiroketals using a chiral sulfoxide auxiliary. Our primary focus was on the synthesis of the 3H-spiro[benzofuran-2,2′-chroman] ring system, the spirocyclic core of the rubromycin family. Our strategy employed the use of lithium–halogen exchange on a racemic bromoSpiroketal in order to attach a chiral sulfoxide, thus producing two diastereomers. The diastereomers were separable, enabling isolation of each Spiroketal enantiomer. Subsequent cleavage of the sulfoxide group from each diastereomer yielded the respective parent Spiroketal in high enantiopurity.
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Synthesis of a 6,6‐Spiroketal Amino Acid and Its Incorporation into a Peptide Turn Sequence Using Solid‐Phase Peptide Synthesis
Chemistry (Weinheim an der Bergstrasse Germany), 2013Co-Authors: Jui Thiang Brian Kueh, Ka Wai Choi, Geoffrey M. Williams, Kerstin Moehle, Bernadett Bacsa, John A. Robinson, Margaret A. BrimbleAbstract:Spiropins for SPPS: The rigid structure of an anomerically stabilised Spiroketal motif enables the appendage of substituents in a fixed conformation. To assess the ability of a Spiroketal motif to induce a turn structure and participate in solid-phase peptide synthesis (SPPS), an Fmoc-Spiroketal amino acid was synthesised and incorporated into a Spiroketal-containing cyclic peptide.
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Telomerase Inhibition Studies of Novel Spiroketal- Containing Rubromycin Derivatives
Australian Journal of Chemistry, 2013Co-Authors: Tsz Ying Yuen, Jack L.‐y. Chen, Darcy J. Atkinson, Jonathan Sperry, Margaret A. BrimbleAbstract:Twenty nine novel Spiroketal derivatives related to the rubromycins were evaluated for their anti-telomerase activity using the real-time quantitative telomeric repeat amplification protocol assay. The parent compound γ-rubromycin exhibited the highest potency against human telomerase activity within the series. Modification of the Spiroketal motif by the introduction of heteroatoms and substituents at different positions produced analogues with varying bioactivity. Variation at the isocoumarin subunit of the title compound resulted in weaker activity, indicative of its importance in telomerase inhibition.
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Synthetic approaches to [5,6]‑benzannulated Spiroketal natural products
Pure and Applied Chemistry, 2011Co-Authors: Michael C. Mcleod, Margaret A. Brimble, Zoe E. Wilson, Dominea C. K. Rathwell, Tsz Ying YuenAbstract:Studies toward the synthesis of three biologically active (5,6)-benzannulated Spiroketal natural products are described. The first total synthesis of paecilospirone is reported, employing a late-stage, pH-neutral Spiroketalization. A formal synthesis of γ-rubromycin is described, where the Spiroketal moiety is formed by delicate manipulation of the electronic properties of the spirocyclization precursor. Finally, model work toward the total synthesis of berkelic acid is summarized, introducing a novel Horner-Wadsworth-Emmons/oxa-Michael (HWE/oxa-M) cascade to access the Spiroketal precursor.
Mark A. Rizzacasa - One of the best experts on this subject based on the ideXlab platform.
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The hetero-Diels-Alder approach to Spiroketals.
Organic & biomolecular chemistry, 2009Co-Authors: Mark A. Rizzacasa, Annett PollexAbstract:The hetero-Diels-Alder reaction can provide Spiroketal systems with excellent stereoselectivity. This perspective article will briefly outline the scope and limitations of this approach for the production of naturally occurring Spiroketals and derivatives.
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Hetero-Diels–Alder synthesis of the Spiroketal fragment of reveromycin A
Tetrahedron Letters, 2000Co-Authors: Mariana El Sous, Mark A. RizzacasaAbstract:The asymmetric synthesis of the 6,6-Spiroketal fragment 15 of the epidermal growth factor inhibitor reveromycin A (1) is described. A hetero-Diels–Alder reaction was utilized to construct the 6,6-Spiroketal 14 and subsequent stereoselective hydroboration provided reveromycin A Spiroketal 15.
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Convergent synthesis of polyether ionophore antibiotics: Synthesis of the Spiroketal and tricyclic glycal segments of monensin
Journal of the American Chemical Society, 1993Co-Authors: Robert E. Ireland, Joseph D. Armstrong, Jacques Lebreton, Robert S. Meissner, Mark A. RizzacasaAbstract:The syntheses of the Spiroketal II and tricyclic glycal III portions of the polyether antibiotic monensin (I) are described. The butyric acid side chain of Spiroketal II is constructed through either Sharpless epoxidation of a cis-2-butenol residue or by Brown crotylation of an α-methylacetaldehyde unit. The Spiroketal is then generated through a hetero-Diels-Alder addition between a tetrahydropyranoid methylene ketone and acrolein. Finally, [6.5] - Spiroketal structure II is prepared by mild acid catalyzed rearrangement of [6.6]-Spiroketal epoxide 23. Glycal III was made from the C/D subunit 44. This subunit was prepared by the ester enolate Claisen rearrangement that unites the tetrahydrofuranoid C and D rings 40 and 41 by Brown crotylation, Wittig condensation, and then cyclization to form the E ring. The synthesis of the two fragments set the stage for a final ester enolate Claisen rearrangement that will form the skeleton of the polyether monensin (I)
Peter G. Goekjian - One of the best experts on this subject based on the ideXlab platform.
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A Concise and Efficient Synthesis of Spiroketals - Application to the Synthesis of SPIKET-P and a Spiroketal from Bactrocera Species
European Journal of Organic Chemistry, 2013Co-Authors: Loïc Tomas, David Gueyrard, Benjamin Bourdon, Jean Claude Caille, Peter G. GoekjianAbstract:We report the synthesis of Spiroketals by sequence of enol ether synthesis and cyclization. The enol ethers were prepared from lactones by a Julia olefination reaction, and the starting chiral lactone was prepared from an industrial intermediate. This route is a concise and efficient way to synthesize naturally occurring and biologically interesting Spiroketals. We used this sequence for the preparation of SPIKET-P and a Spiroketal from Bactrocera species.
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A Concise and Efficient Synthesis of Spiroketals – Application to the Synthesis of SPIKET-P and a Spiroketal from Bactrocera Species
European Journal of Organic Chemistry, 2013Co-Authors: Loïc Tomas, David Gueyrard, Benjamin Bourdon, Jean Claude Caille, Peter G. GoekjianAbstract:We report the synthesis of Spiroketals by sequence of enol ether synthesis and cyclization. The enol ethers were prepared from lactones by a Julia olefination reaction, and the starting chiral lactone was prepared from an industrial intermediate. This route is a concise and efficient way to synthesize naturally occurring and biologically interesting Spiroketals. We used this sequence for the preparation of SPIKET-P and a Spiroketal from Bactrocera species.
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A Concise and Efficient Synthesis of Spiroketals – Application to the Synthesis of SPIKET‐P and a Spiroketal from Bactrocera Species
European Journal of Organic Chemistry, 2013Co-Authors: Loïc Tomas, David Gueyrard, Benjamin Bourdon, Jean Claude Caille, Peter G. GoekjianAbstract:We report the synthesis of Spiroketals by sequence of enol ether synthesis and cyclization. The enol ethers were prepared from lactones by a Julia olefination reaction, and the starting chiral lactone was prepared from an industrial intermediate. This route is a concise and efficient way to synthesize naturally occurring and biologically interesting Spiroketals. We used this sequence for the preparation of SPIKET-P and a Spiroketal from Bactrocera species.
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A Julia olefination approach to the synthesis of functionalized enol ethers and their transformation into carbohydrate-derived Spiroketals
Tetrahedron Letters, 2008Co-Authors: Matthieu Corbet, David Gueyrard, Benjamin Bourdon, Peter G. GoekjianAbstract:A synthesis of Spiroketals from carbohydrate lactones is reported. A modified Julia olefination is used to synthesize trisubstituted and highly functionalized exo-glycals, which were subsequently transformed into Spiroketals under acidic conditions.
Tsz Ying Yuen - One of the best experts on this subject based on the ideXlab platform.
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Telomerase Inhibition Studies of Novel Spiroketal- Containing Rubromycin Derivatives
Australian Journal of Chemistry, 2013Co-Authors: Tsz Ying Yuen, Jack L.‐y. Chen, Darcy J. Atkinson, Jonathan Sperry, Margaret A. BrimbleAbstract:Twenty nine novel Spiroketal derivatives related to the rubromycins were evaluated for their anti-telomerase activity using the real-time quantitative telomeric repeat amplification protocol assay. The parent compound γ-rubromycin exhibited the highest potency against human telomerase activity within the series. Modification of the Spiroketal motif by the introduction of heteroatoms and substituents at different positions produced analogues with varying bioactivity. Variation at the isocoumarin subunit of the title compound resulted in weaker activity, indicative of its importance in telomerase inhibition.
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Synthetic approaches to [5,6]‑benzannulated Spiroketal natural products
Pure and Applied Chemistry, 2011Co-Authors: Michael C. Mcleod, Margaret A. Brimble, Zoe E. Wilson, Dominea C. K. Rathwell, Tsz Ying YuenAbstract:Studies toward the synthesis of three biologically active (5,6)-benzannulated Spiroketal natural products are described. The first total synthesis of paecilospirone is reported, employing a late-stage, pH-neutral Spiroketalization. A formal synthesis of γ-rubromycin is described, where the Spiroketal moiety is formed by delicate manipulation of the electronic properties of the spirocyclization precursor. Finally, model work toward the total synthesis of berkelic acid is summarized, introducing a novel Horner-Wadsworth-Emmons/oxa-Michael (HWE/oxa-M) cascade to access the Spiroketal precursor.
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synthetic approaches to 5 6 benzannulated Spiroketal natural products
Pure and Applied Chemistry, 2011Co-Authors: Michael C. Mcleod, Margaret A. Brimble, Zoe E. Wilson, Dominea C. K. Rathwell, Tsz Ying YuenAbstract:Studies toward the synthesis of three biologically active (5,6)-benzannulated Spiroketal natural products are described. The first total synthesis of paecilospirone is reported, employing a late-stage, pH-neutral Spiroketalization. A formal synthesis of γ-rubromycin is described, where the Spiroketal moiety is formed by delicate manipulation of the electronic properties of the spirocyclization precursor. Finally, model work toward the total synthesis of berkelic acid is summarized, introducing a novel Horner-Wadsworth-Emmons/oxa-Michael (HWE/oxa-M) cascade to access the Spiroketal precursor.
Michael T. Crimmins - One of the best experts on this subject based on the ideXlab platform.
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A Modular, Stereoselective Approach to Spiroketal Synthesis
Synlett, 2012Co-Authors: Michael T. Crimmins, Adam M. AzmanAbstract:A highly convergent and flexible synthetic approach to stereochemically defined Spiroketals is reported. Substituents can be incorporated at various positions around the Spiroketal framework without significant disruption to the synthetic scheme. The approach has been exploited to prepare the Spiroketal fragment of milbemycin β14.
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letterStereoselective Approach to Spiroketal Synthesis
2012Co-Authors: Michael T. Crimmins, Adam M. AzmanAbstract:A highly convergent and flexible synthetic approach to stereochemically defined Spiroketals is reported. Substituents can be incorporated at various positions around the Spiroketal frame- work without significant disruption to the synthetic scheme. The ap- proach has been exploited to prepare the Spiroketal fragment of milbemycin β14.
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Synthesis of the C16-C28 Spiroketal subunit of spongistatin 1 (altohyrtin A): the pyrone approach.
Organic letters, 2000Co-Authors: Michael T. Crimmins, Jason D. KatzAbstract:The synthesis of the CD Spiroketal fragment of spongistatin 1 (altohyrtin A) has been accomplished utilizing the addition of a metalated pyrone to an aldehyde and subsequent acid-catalyzed spirocyclization. A stereoselective hydrogenation and subsequent conformational inversion establish the C19 stereocenter and the axial−equatorial Spiroketal center.
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Addition of metalated pyrones to β-alkoxy aldehydes: Synthesis of hydroxylated Spiroketals
Tetrahedron Letters, 1998Co-Authors: Michael T. Crimmins, David G. Washburn, Jason D. Katz, Frank J. ZawackiAbstract:Abstract Addition of lithiated γ-pyrones to β-alkoxy aldehydes followed by acid catalyzed Spiroketalization provides a rapid efficient entry to functionalized hydroxylated Spiroketals. The efficiency of the Spiroketalization step is dependent on the substituents, particularly unprotected hydroxyls, on the chain which becomes the second ring of the Spiroketal.
