- Double diastereoselection in intramolecular photocycloadditions: A radical rearrangement approach to the total synthesis of the spirovetivane phytoalexin (±)-lubiminol
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The highly stereoselective total synthesis of the phytoalexin (±)-lubiminol (1) has been accomplished. The synthesis relies on three pivotal transformations: (1) a conjugate addition-cyclization reaction to prepare a highly functionalized 2-carbomethoxycyclopentenone as a photocycloaddition substrate, (2) a double diastereoselective intramolecular photocycloaddition for a stereoselective intramolecular photoaddition reaction which establishes the central quaternary spirocenter, and (3) the transformation of the photoadduct into the required spiro[5.4]decane through a radical fragmentation-rearrrangement reaction.
- Crimmins, Michael T.,Wang, Zhuo,McKerlie, Lynne A.
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- 2,3-cis-Cyclization of 4-pentenoxyl radicals
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4-Pentenoxyl radicals cyclize 2,3-cis-selectively, when substituted by an allylic hydroxy, acetyloxy, or benzoyloxy group. Additional substituents increase or decrease the fraction of 2,3-cis-cyclized product, depending on relative configuration, position
- Kempter, Irina,Schur, Christine,Huttenlochner, Katharina,Bergstr??er, Ruth-Maria,Wolff, Benjamin,Kopf, Thomas,Hartung, Jens
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- Rearrangement of cyclobutyl carbinyl radicals: Total synthesis of the spirovetivane phytoalexin (±)-lubiminol
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The total synthesis of the phytoalexin (±)-lubiminol 1 has been accomplished. The synthesis relies on a conjugate addition-cyclization reaction to prepare a photosubstrate for a stereoselective intramolecular photoaddition reaction. The photoadduct is and formed into the required spiro [5.4] decane through a radical fragmentation-rearrangement reaction.
- Crimmins, Michael T.,Wang, Zhuo,McKerlie, Lynne A.
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- Total Synthesis of an Isatis indigotica-Derived Alkaloid Using a Biomimetic Thio-Diels-Alder Reaction
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A biomimetic thio-Diels-Alder reaction between a dienylthiadiazole and 3-thioisatin leads to the Isatis indigotica-derived alkaloid (1), along with its diastereomer 2. This synthetic study, supported by molecular modeling, establishes the viability of the proposed biosynthesis by thio-Diels-Alder cycloaddition, a very rare reaction in nature. Moreover, the results described infer that the diastereomer 2 is an as-yet undiscovered natural product present in Isatis indigotica.
- Davison, Emma K.,Hume, Paul A.,Sperry, Jonathan
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- Total synthesis of PGF2α and 6,15-diketo-PGF1α and formal synthesis of 6-keto-PGF1α via three-component coupling
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The asymmetric total synthesis of PGF2α and 6,15-diketo-PGF1α and formal synthesis of 6-keto-PGF1α from a common key intermediate are described. The key intermediate, which has a chiral cyclopentane backbone possessing suitable functional groups with required stereochemistry for both side chains, was prepared from (R)-4-silyloxy-2-cyclopentenone through a three-component coupling reaction. The Wittig reaction, Nozaki-Hiyama-Kishi (NHK) coupling and cross metathesis completed the synthesis of PGF2α, 6,15-diketo-PGF1α and 6-keto-PGF1α.
- Kim, Taehyeong,Lee, Sung Il,Kim, Sejin,Shim, Su Yong,Ryu, Do Hyun
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supporting information
(2019/09/17)
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- Continuous Pd-Catalyzed Carbonylative Cyclization Using Iron Pentacarbonyl as a CO Source
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This work discloses a continuous flow carbonylation reaction using iron pentacarbonyl as source of CO. The described transformation using this surrogate was designed for use in commonly accessible flow equipment. Optimized conditions were applied to a sca
- Lopatka, Pavol,Markovi?, Martin,Koó?, Peter,Ley, Steven V.,Gracza, Tibor
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p. 14394 - 14406
(2019/11/11)
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- Rhodium-Catalyzed Cyclization of O,ω-Unsaturated Alkoxyamines: Formation of Oxygen-Containing Heterocycles
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O,ω-Unsaturated N-tosyl alkoxyamines undergo unexpected RhIII-catalyzed intramolecular cyclization by oxyamination to produce oxygen-containing heterocycles. Mechanistic studies show that an aziridine intermediate seems to be responsible for the formation of the heterocycles, possibly via a RhV species.
- Escudero, Julien,Bellosta, Véronique,Cossy, Janine
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supporting information
p. 574 - 578
(2018/02/21)
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- Scalable synthesis enabling multilevel bio-evaluations of natural products for discovery of lead compounds
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Challenges in the development of anti-cancer chemotherapeutics continue to exist, particularly with respect to adverse effects and development of resistance, underlining the need for novel drugs with good safety profiles. Natural products have proven to be a fertile ground for exploitation, and development of anti-cancer drugs from structurally complex natural products holds promise. Unfortunately, this approach is often hindered by low isolation yields and limited information from preliminary cell-based assays. Here we report a concise and scalable synthesis of a series of low-Abundance Isodon diterpenoids (a large class of natural products with over 1000 members isolated from the herbs of genus Isodon, which are well-known folk medicines for the treatment of inflammation and cancer), including eriocalyxin B, neolaxiflorin L and xerophilusin I. These scalable syntheses enable multilevel bio-evaluation of the natural products, in which we identify neolaxiflorin L as a promising anti-cancer drug candidate.
- Zhu, Lizhi,Ma, Wenjing,Zhang, Mengxun,Lee, Magnolia Muk-Lan,Wong, Wing-Yan,Chan, Brandon Dow,Yang, Qianqian,Wong, Wing-Tak,Tai, William Chi-Shing,Lee, Chi-Sing
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- Rhodium Carbenoid Initiated O-H Insertion/Aldol/Oxy-Cope Cascade for the Stereoselective Synthesis of Functionalized Oxacycles
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A novel diazo-cascade approach has been developed for the synthesis of nine-membered oxacycles utilizing readily accessible β-hydroxy vinyl ketones and vinyl diazo esters. The Rh(II)-catalyzed cascade reaction begins with carbene O-H insertion followed by an intramolecular aldol cyclization to provide a substituted tetrahydrofuran intermediate that undergoes an oxy-Cope rearrangement to provide functionalized nine-membered oxacycles with complete stereoselectivity.
- Chinthapally, Kiran,Massaro, Nicholas P.,Sharma, Indrajeet
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supporting information
p. 6340 - 6343
(2016/12/23)
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- Synthesis of functionalized 1-azabicyclo[3.1.0]hexanes: Studies towards ficellomycin and its analogs
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The molecule of antibiotic agent ficellomycin contains an intriguing array of functional groups assembled around a bicyclic aziridine core. To address the challenges of constructing ficellomycin derivatives, we have developed cycloamination methodology fo
- Chen, Gang,He, Zhi,Yudin, Andrei K.
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p. 1299 - 1310
(2016/10/06)
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- New facile enantio- and diastereo-selective syntheses of (-)-triptonide and (-)-triptolide
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A novel formal asymmetric synthesis of (-)-triptonide and (-)-triptolide, featuring a new alternative access to their known key intermediate 4, has been achieved through two synthetic routes in 9 steps with 13.6% total yield and 10 steps with 18.5% overall yield, respectively. This synthesis is scalable and hence has high potential for application to further synthetic elaboration and biologic investigation on such natural products.
- Zhang, Hongrui,Li, Haifeng,Xue, Jijun,Chen, Rui,Li, Ying,Tang, Yu,Li, Chunxin
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supporting information
p. 732 - 736
(2014/01/23)
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- New and concise syntheses of the bicyclic oxamazin core using an intramolecular nitroso diels-alder reaction and ring-closing olefin metathesis
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Herein two new and concise synthetic approaches for making an unsaturated bicyclic oxamazin core are reported. The first involves the use of an intramolecular Diels-Alder reaction to form both of the fused rings in one step. The second approach incorporates ring-closing olefin metathesis in the final step to form the second fused ring of the core. The scope of the second approach was also expanded further to afford larger ringed bicyclic systems.
- Watson, Kyle D.,Carosso, Serena,Miller, Marvin J.
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p. 358 - 361
(2013/03/13)
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- Total syntheses of naturally occurring seimatopolide A and its enantiomer from chiral pool starting materials using a bidirectional strategy
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Enantioselective total syntheses of both enantiomers of the recently isolated decanolide natural product seimatopolide A are described. The C 2-symmetric building blocks (R,R)-hexa-1,5-diene-3,4-diol (derived from d-mannitol) and its enantiomer (derived from l-(+)-tartrate) serve as key starting materials, which are elaborated in a bidirectional way using a selective mono-cross-metathesis, regio-and stereoselective epoxidation, and regioselective reductive epoxide opening to furnish the first fragment. Both enantiomers of the second fragment, 3-hydroxypent-4-enoic acid, were conveniently obtained through a lipase-catalyzed kinetic resolution and merged with the first fragment via Shiina esterification. An E-selective ring-closing metathesis was used to access the 10-membered lactone. A comparison of the specific optical rotations of synthetic seimatopolides with those reported for the natural product suggests that the originally assigned (3R,6R,7R,9S)- configuration should be corrected to (3S,6S,7S,9R).
- Schmidt, Bernd,Kunz, Oliver,Petersen, Monib H.
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p. 10897 - 10906
(2013/02/22)
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- A facile synthesis of α-fluoro ketones catalyzed by [Cp*IrCl2]2
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Allylic alcohols are isomerized into enolates (enols) by [Cp*IrCl2]2. The enolates react with Selectfluor present in the reaction media. This method produces α-fluoro ketones as single constitutional isomers in high yields. Georg Thieme Verlag Stuttgart. New York.
- Ahlsten, Nanna,Bartoszewicz, Agnieszka,Agrawal, Santosh,Martin-Matute, Belen
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supporting information; experimental part
p. 2600 - 2608
(2011/10/02)
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- Synthesis and evaluation of substrate analogues as mechanism-based inhibitors of type II isopentenyl diphosphate isomerase
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(Chemical Equation Presented) Type 2 isopentenyl diphosphate isomerase (IDI-2), which catalyzes the interconversion of isopentenyl diphosphate and dimethylallyl diphosphate, contains a tightly bound molecule of FMN. To probe the mechanism of the reaction,
- Walker, Joel R.,Rothman, Steven C.,Poulter, C. Dale
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p. 726 - 729
(2008/09/17)
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- Palladium-catalyzed arylation of α,α-difluoro-allylic-β-hydroxyester
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The aryl-substituted α,α-difluoro-allylic-β-hydroxyesters and aryl-substituted α,α-difluoroketones were obtained via the coupling reaction of aryl iodides with α,α-difluoro-allylic-β-hydroxyester in the presence of Pd(OAc)2 as the catalyst and Et3N as the base.
- Fang, Xiang,Yang, Xueyan,Yang, Xianjin,Zhao, Min,Chen, Guorong,Wu, Fanhong
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p. 8231 - 8234
(2007/10/03)
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- Ruthenium-catalyzed tandem ring closing metathesis (RCM) - Atom transfer radical cyclization (ATRC) sequences
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α-ω-Dienes bearing a pendant trichloroacetoxy group undergo a tandem RCM - radical cycloisomerization sequence leading to bicyclic γ-butyrolactones, with both steps of the sequence being catalyzed by ruthenium.
- Schmidt, Bernd,Pohler, Michael
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p. 5552 - 5555
(2007/10/03)
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- Synthesis of isotetronic acids by cyclization of 1,3-bis(trimethylsilyloxy) alk-1-enes with oxalyl chloride
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Isotetronic acids were regioselectively prepared by cyclization of 1,3-bis(trimethylsilyloxy)alk-1-enes with oxalyl chloride.
- Dede, Rüdiger,Michaelis, Lars,Langer, Peter
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p. 8129 - 8131
(2007/10/03)
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- Stereoselective synthesis of the ABC ring system of norzoanthamine
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(Equation presented) An efficient synthesis of enone 4, representing the ABC ring motif of norzoanthamine, is presented. The crucial C22 quaternary center was introduced via a stereoselective methylation of enone 8. The trans-anti-trans relative configura
- Ghosh, Subhash,Rivas, Fatima,Fischer, Derek,Gonzalez, Miguel A.,Theodorakis, Emmanuel A.
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p. 941 - 944
(2007/10/03)
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- Enantioselective synthesis of the antiinflammatory agent (-)-acanthoic acid
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An enantioselective synthesis of the potent antiinflammatory agent (-)-acanthoic acid (1) is described. The successful strategy departs from (-)-Wieland-Miescher ketone (10), which is readily available in both enantiomeric forms and constitutes the starting point toward a fully functionalized AB ring system of 1. Conditions were developed for a regioselective double alkylation at the C4 center of the A ring, which produced compound 32 as a single stereoisomer. Construction of the C ring of 1 was accomplished via a Diels-Alder reaction between sulfur-containing diene 43 and methacrolein (36), which after desulfurization and further functionalization yielded synthetic acanthoic acid. The described synthesis confirms the proposed stereochemistry of the natural product and represents a fully stereocontrolled entry into an underexplored class of biologically active diterpenes.
- Ling,Chowdhury,Kramer,Vong,Palladino,Theodorakis
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p. 8843 - 8853
(2007/10/03)
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- Synthesis of acyclic carba-nucleoside phosphonates, structural analogues to natural deoxyribonucleotides
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Acyclic carba-nucleoside phosphonates, modelled on natural deoxyribonucleotides have been prepared starting from DNA nucleobases and tert-butyl acrylate. The products obtained from a Michael-type reaction were elongated to β-oxo esters that were first reduced to β-hydroxy esters and then transformed into protected β-hydroxy aldehydes. Wittig-Homer-Emmons reaction with the anion of tetraisopropyl methylenebisphosphonate gave, after deprotection, the desired 4-hydroxy-6-purinyl- or -6-pyrimidinyl-1- hexenylphosphonic acids. A dimer, potential precursor of acyctic polynucleotides (APN), homomorphous with DNA, was also prepared.
- Esposito, Annamaria,Perino, Maria Grazia,Taddei, Maurizio
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p. 931 - 936
(2007/10/03)
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- Intramolecular cyclisation of (Z)-N-4-alkenylnitrones and the effects of alkenyl substituents
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The intramolecular 1,3-dipolar cycloaddition reactions of (Z)-N-4- alkenylnitrones carrying various alkenyl substituents were investigated, and the regiochemistry of the resulting isoxazolidines was determined. Silyl-and bromo-substituents were found to effect significant regiocontol on the intramolecular nitrone dipolar cycloaddition reaction.
- Hems,Tan,Stork,Feeder,Holmes
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p. 1393 - 1396
(2007/10/03)
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- Biomimetic cyclisation of prebrevetoxin polyepoxide models
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(E)-1,3-Dihydroxyhex-4-ene and (E)-1,3-dihydroxy-4-methylhex-4-ene undergo epoxidation with peracetic acid and in situ cyclisation to give a mixture of tetrahydro-furans and -pyrans, whereas comparable compounds lacking the allylic hydroxyl group give pre
- Kelly, David R.,Nally, James
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p. 3251 - 3254
(2007/10/03)
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- Synthesis and intramolecular photocycloadditions of 2-acyloxy-3-hexenoyl cyclohexenones: Diastereoselectivity in the intramolecular [2+2] photocycloadditions of alkenes and cyclohexenones tethered by four atoms
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The intramolecular [2+2] photocycloaddition of 2-acyloxy-2-3- hexenoylcyclohexenones has been shown to be highly diastereoselective. The cycloadditions produce exclusively cis fused products and the sense and level of selectivity is consistent with a molecular mechanics model for initial bond formation in the stepwise cycloaddition.
- Crimmins, Michael T.,King, Bryan W.,Watson, Paul S.,Guise, Lisa E.
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p. 8963 - 8974
(2007/10/03)
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