137 results found
Allen LAT, Raclea R-C, Natho P, et al., 2021, Recent advances in the synthesis of α-amino ketones, Organic & Biomolecular Chemistry, Vol: 19, Pages: 498-513, ISSN: 1477-0520
<p>This review on α-amino ketone synthesis collates and evaluates developments made in this area over the past decade, with an extended discussion on functional group compatibility, resultant product substitution patterns, and medicinal applications.</p>
Mies T, White AJP, Parsons PJ, et al., 2021, Conversion of 5-methyl-4H-benzo[d][1,3]dioxin-4-one derivatives into functionalized 8-hydroxyisochroman-1-one under basic conditions, TETRAHEDRON LETTERS, Vol: 81, ISSN: 0040-4039
Mies T, Patel C, Parsons PJ, et al., 2021, Biomimetic total syntheses of amorfrutins A, B, (S)-D and (R)-D and formal synthesis of amorfrutin C, European Journal of Organic Chemistry, Vol: 2021, Pages: 2540-2548, ISSN: 1099-0690
Bibenzyl natural products, such as the amorfrutins, contain a heavily substituted aromatic core and display a diverse range of biological activities (anti-tumor, anti-diabetic, antimicrobial, and antibiotic). In this study, we report unified syntheses of amorfrutin A to D either through total or formal synthesis by employing a dual biomimetic strategy of polyketide aromatization followed by remote terpene functionalization. The key core structures were synthesized from β-keto dioxinone esters through a magnesium(II) mediated regioselective C-acylation, palladium catalyzed decarboxylative allylic rearrangement, and dehydrative cyclization.
Patel C, Mies T, White AJP, et al., 2021, Biomimetic syntheses of amorfrutin C and C-5 substituted amorfrutin analogues, European Journal of Organic Chemistry, Vol: 2021, Pages: 1258-1265, ISSN: 1099-0690
Amorfrutin C, a C-5 prenyl amorfrutin, its allyl analog and an amorfrutin C-5 aldehyde have been synthesized using a biomimetic strategy from non-aromatic precursors. In this approach, a dioxinone derived β,δ-diketo ester underwent a decarboxylative Pd(0) catalyzed prenyl migration to give a β,δ-diketo dioxinone, which readily aromatized giving the amorfrutin core. The introduction of prenyl and allyl moieties at the C-5 position of the scaffold was accomplished using a Claisen rearrangement. Alternatively, iodination, lithium-iodine exchange and trapping with DMF gave the amorfrutin aldehyde and an amorfrutin alcohol when excess n-BuLi was used.
Petti A, Natho P, Lam K, et al., 2021, Regioselective Electrochemical Cyclobutanol Ring Expansion to 1‐Tetralones, European Journal of Organic Chemistry, Vol: 2021, Pages: 854-858, ISSN: 1434-193X
Mies T, White AJP, Parsons PJ, et al., 2021, Biomimetic syntheses of analogs of hongoquercin A and B by late-stage derivatization, Journal of Organic Chemistry, Vol: 86, Pages: 1802-1817, ISSN: 0022-3263
The hongoquercins are tetracyclic meroterpenoid natural products with the trans–transoid decalin-dihydrobenzopyran ring system, which display a range of different bioactivities. In this study, the syntheses of a range of hongoquercins using gold-catalyzed enyne cyclization reactions and further derivatization are described. The parent enyne resorcylate precursors were synthesized biomimetically from the corresponding dioxinone keto ester via regioselective acylation, Tsuji-Trost allylic decarboxylative rearrangement, and aromatization. The dioxinone keto ester 12 was prepared in 6 steps from geraniol using allylic functionalization and alkyne synthesis.
Natho P, Yang T, Allen L, et al., 2021, An entry to 2-(cyclobut-1-en-1-yl)-1H-indoles through a cyclobutenylation/deprotection cascade, Organic and Biomolecular Chemistry, ISSN: 1477-0520
Natho P, Annie R, Greenfield J, et al., 2020, Regioselective synthesis of 1- and 4-tetralones from heteroaryl-3-cyclobutanols, Tetrahedron, Vol: 76, ISSN: 0040-4020
Herein we describe the first transition-metal-free ring expansion of four-membered rings to 1-tetralones from 3-substituted heteroaromatic compounds, and the first example of an oxetanol ring expansion to an oxa-tetralone. We also experimentally investigate the mechanism of the silver-mediated ring expansion and elucidate the active oxidant in these systems using electrochemical techniques.
Raclea R-C, Natho P, Allen LAT, et al., 2020, Oxidative Deconstruction of Azetidinols to α-Amino Ketones, The Journal of Organic Chemistry, Vol: 85, Pages: 9375-9385, ISSN: 0022-3263
Natho P, Allen LAT, Parsons PJ, 2020, Recent advances in the ring expansion of cyclobutanols, oxetanols, and azetidinols, Tetrahedron Letters, Vol: 61, Pages: 1-9, ISSN: 0040-4039
The number of developed methodologies for the ring expansion of cyclobutanol rings to five, six and seven-membered rings has increased significantly over the last six years. In this timeframe, the semipinacol rearrangement of vinyl-group containing cyclobutanols to cyclopentanones has been advanced under photoredox and electrochemical conditions, enabling the concomitant introduction of a wide array of functional groups. The expansion to 1- and 4-tetralones has been achieved for the first time under transition-metal-free conditions and even expansion to seven-membered rings has been demonstrated under rhodium catalysis. In this article, we will critically discuss the scope, application and mechanistic studies of procedures published since 2013, and provide a short outlook on the emerging potential for further development in this area.
Ma T-K, Parsons P, Barrett A, 2020, Synthesis, aromatization and derivatization reactions of 2-(9-(tert-butoxycarbonyl)-4-oxo-1,5-dioxa-9-azaspiro[5.5]undec-2-en-2-yl)acetic acid, European Journal of Organic Chemistry, Vol: 2020, Pages: 28-34, ISSN: 1434-193X
A series of natural product inspired piperidines spiro‐fused with resorcylic, chromenic and chromanic amides were prepared from a general derivative of a N ‐Boc‐4‐oxo‐4 H ‐spiro[benzo[ d ][1,3]dioxinone‐2,4‐piperidine], which was prepared via biomimetic aromatization of a b , d ‐diketo‐dioxinone, in turn synthesized from N ‐Boc‐4‐piperidone and geraniol using ketene coupling reagents.
Ma T-K, Parsons PJ, Barrett AGM, 2020, Front cover: synthesis, aromatization and derivatization reactions of 2-[9-(tert-Butoxycarbonyl)-4-oxo-1,5-dioxa-9-azaspiro[5.5]undec-2-en-2-yl]acetic Acid (Eur. J. Org. Chem. 1/2020), European Journal of Organic Chemistry, Vol: 2020, Pages: 1-1, ISSN: 1434-193X
The Front Cover shows novel spiro‐fused piperidines with resorcylic, chromenic, and chromanic carboxamides. These were synthesized from 2‐(9‐Boc)‐4‐oxo‐1,5‐dioxa‐9‐azaspiro[5.5]undec‐2‐en‐2‐yl)acetic acid by sequential DCC mediated coupling with 2‐phenyl‐1,3‐dioxane‐4,6‐dione, keto‐ketene generation and trapping with geraniol, biomimetic aromatization by palladium catalyzed decarboxylation and cyclization. The resultant spiro‐resorcylate was derivatized by terpene cyclization and/or Boc‐deprotection with reacylation to provide the spiro‐heterocyclic products. We thank Murray Robertson, Visual Elements, for creating the artwork. More information can be found in the Full Paper by A. G. M. Barrett et al (https://doi.org/10.1002/ejoc.201901451).
Natho P, Allen LAT, White AJP, et al., 2019, A transition-metal-free access to heteroaromatic-fused 4-tetralones by the oxidative ring expansion of the cyclobutanol moiety, The Journal of Organic Chemistry, Vol: 84, Pages: 9611-9626, ISSN: 0022-3263
Advances in the transition-metal-free cyclobutanol ring expansion to 4-tetralones under N-bromosuccinimide mediation are described. We have expanded the scope of this ring expansion methodology and investigated the effect substituents on the aromatic ring, and the cyclobutanol moiety, have on the outcome of the reaction. Limitations with certain substituents on the cyclobutanol moiety are also described. Further experimental evidence to support our mechanistic understanding is disclosed, and we now preclude the suggested involvement of a primary radical for this transformation.
Ma T-K, Parsons PJ, Barrett AGM, 2019, Meroterpenoid synthesis via sequential polyketide aromatization and radical anion cascade triene cyclization: Biomimetic total syntheses of austalide natural products, The Journal of Organic Chemistry, Vol: 84, Pages: 4961-4970, ISSN: 0022-3263
The first total synthesis of five austalide natural products, (±)-17S-dihydroaustalide K, (±)-austalide K, (±)-13-deacetoxyaustalide I, (±)-austalide P, and (±)-13-deoxyaustalide Q acid, was accomplished via a series of biomimetic transformations. Key steps involved polyketide aromatization of a trans,trans-farnesol-derived β,δ-diketodioxinone into the corresponding β-resorcylate, followed by titanium(III)-mediated reductive radical cyclization of an epoxide to furnish the drimene core. Subsequent phenylselenonium ion induced diastereoselective cyclization of the drimene completed the essential carbon framework of the austalides to access (±)-17S-dihydroaustalide K, (±)-austalide K, and (±)-13-deacetoxyaustalide I via sequential oxidations. Furthermore, (±)-13-deacetoxyaustalide I could serve as a common intermediate to be derivatized into other related natural products, (±)-austalide P and (±)-13-deoxyaustalide Q acid, by functionalizing the cyclic lactone moiety.
Natho P, Kapun M, Allen L, et al., 2018, Regioselective transition-metal-free oxidative cyclobutanol ring expansion to 4-tetralones, Organic Letters, Vol: 20, Pages: 8030-8034, ISSN: 1523-7052
A facile and transition-metal-free ring expansion of the cyclobutanol moiety to 4-tetralones fused to heteroaromatic systems is described. The oxidative ring expansion proceeds rapidly and regioselectively through mediation by N-bromosuccinimide and acetonitrile in satisfactory to good yields. The preparation of precursors, as well as the ring expansion have proven to be scalable and are straightforward to carry out
Ma T-K, Elliott DC, Reid S, et al., 2018, Meroterpenoid synthesis via sequential polyketide aromatization and cationic polyene cyclization: total syntheses of (+)-Hongoquercin A and B and related meroterpenoids., Journal of Organic Chemistry, Vol: 83, Pages: 13276-13286, ISSN: 0022-3263
(+)-Hongoquercin A and B were synthesized from commercially available trans, trans-farnesol in six and eleven steps, respectively, using dual biomimetic strategies with polyketide aromatization and subsequent polyene functionalization from a common farnesyl-resorcylate intermediate. Key steps involve Pd(0)-catalyzed decarboxylative allylic rearrangement of a dioxinone β,δ-diketo ester to a β,δ-diketo dioxinone, which was readily aromatized into the corresponding resorcylate, and subsequent polyene cyclization via enantioselective protonation or regioselective terminal alkene oxidation and cationic cyclization of enantiomerically enriched epoxide to furnish the tetracyclic natural product cores. Analogues of the hongoquercin were synthesized via halonium-induced polyene cyclizations, and the meroterpenoid could be further functionalized via saponification, hydrolytic decarboxylation, reduction, and amidation reactions.
Almond-Thynne J, Han J, White AJP, et al., 2018, Bidirectional synthesis of di-t-butyl (2S,6S,8S)- and (2R,6R,8R)-1,7-diazaspiro[5.5]undecane-2,8-dicarboxylate and related spirodiamines, Journal of Organic Chemistry, Vol: 83, Pages: 6783-6787, ISSN: 0022-3263
Efficient syntheses of both enantiomers of a spirodiamine diester from (L)- and (D)-aspartic acid are described. The key transformation was the conversion of Boc-protected t-butyl aspartate into the derived aldehyde, two directional Horner Emmons olefination, hydrogenation and selective acid-catalyzed Boc-deprotection and spirocyclization. An alternative, two-directional approaches to derivatives of 1,7-diazaspiro[5.5]undecane is described.
Parsons PJ, Allen LAT, Jones DR, et al., 2017, Approaches to the synthesis of highly substituted aromatic and fused rings: metal-catalysed versus thermal cyclisation, Synthesis, Vol: 50, Pages: 84-101, ISSN: 0039-7881
A domino reaction has been used for the construction of lactonamycin derivatives. This research led to a comparison study between palladium-mediated cascade cyclisations and thermal alkyne [2+2+2] cyclisations. A palladium-mediated cyclisation of alkenyl bromides with alkynes and furans has been shown to furnish highly substituted aromatic rings. Penta- and hexasubstituted aromatic rings have also been prepared by the thermolysis of suitably substituted alkynes under microwave conditions. Tetrasubstituted pyridines can also be prepared using nitriles instead of alkynes. This work will provide a new and interesting array of drug templates; mechanistic details are discussed for both reaction series.
Stork G, Yamashita A, Hanson RM, et al., 2017, Synthetic Study toward Total Synthesis of (±)-Germine: Synthesis of (±)-4-Methylenegermine, Organic Letters, Vol: 19, Pages: 5150-5153, ISSN: 1523-7052
The total synthesis of 4-methylenegermine is described.
Almond-Thynne J, White AJP, Polyzos A, et al., 2017, Synthesis and reactions of benzannulated spiroaminals: tetrahydrospirobiquinolines, ACS Omega, Vol: 2, Pages: 3241-3249, ISSN: 2470-1343
An efficient two-step synthesis of symmetrical and unsymmetrical tetrahydrospirobiquinolines from o-azidobenzaldehydes is reported. A novel series of tetrahydrospirobiquinolines was prepared by sequential double-aldol condensation with acetone, cyclopentanone, and cyclohexanone to form the corresponding o,o′-diazido-dibenzylidene-acetone, -cyclopentanone, and -cyclohexanone derivatives, respectively, and hydrogenation–spirocyclization. The spirodiamines were further derivatized by electrophilic aromatic bromination, Suzuki coupling, and N-alkylation, all of which proceeded with preservation of the spirocyclic core.
A cascade reaction has been developed for the synthesis of lactonamycin. In this paper, we demonstrate that a transition-metal-free thermal ene–diyne cyclization can be used for the construction of the entire core of the antibiotic lactonamycin and anticancer agent lactonamycin Z.
Barrett AGM, Elliott D, Ma T, et al., 2016, Sequential Ketene Generation from Dioxane-4,6-dione-keto-dioxinones for the Synthesis of Terpenoid Resorcylates, Organic Letters, Vol: 18, Pages: 1800-1803, ISSN: 1523-7060
Trapping of the ketene generated from the thermolysis of 2-methyl-2-phenyl-1,3-dioxane-4,6-dione-ketodioxinoneat 50 °C with primary, secondary, or tertiary alcohols gave the corresponding dioxinone β-keto-esters in good yieldunder neutral conditions. These intermediates were converted by palladium(0)-catalyzed decarboxylative allyl migration andaromatization into the corresponding β-resorcylates. These transformations were applied to the syntheses of the natural products(±)-cannabiorcichromenic and (±)-daurichromenic acid.
Parsons PJ, Jones DR, Padgham AC, et al., 2016, A New Approach for the Synthesis of Highly Substituted Aromatic Rings: The Alkyne-Mediated Approach, CHEMISTRY-A EUROPEAN JOURNAL, Vol: 22, Pages: 3981-3984, ISSN: 0947-6539
Parsons PJ, Rushton SPG, Panta RR, et al., 2011, New synthetic routes to the kainoids: a synthesis of kainic acid and its analogues, TETRAHEDRON, Vol: 67, Pages: 10267-10273, ISSN: 0040-4020
Parsons PJ, Cooper N, Renshaw M, et al., 2011, A Remarkable Multicomponent Cascade Sequence for the Formation of a Spirocyclic Polyether, Organic Letters, Vol: 13, Pages: 3834-3836
KNIGHT J, PARSONS PJ, 2010, ChemInform Abstract: Radical Approaches to the Synthesis of β-Lactam Antibiotics, ChemInform, Vol: 23, Pages: no-no, ISSN: 0931-7597
Schweizer S, Tokan WM, Parsons PJ, et al., 2010, Palladium-Catalyzed Oligocyclizations of 2-Bromoalka-1,dienynes
EDWARDS N, MACRITCHIE JA, PARSONS PJ, et al., 2010, ChemInform Abstract: Chemistry of Allene Sulfoxides: A New Synthesis of 1-Aryl-3,4-dihydro-1H-benzothieno[3,2-c]pyrans., ChemInform, Vol: 29, Pages: no-no, ISSN: 0931-7597
Parsons PJ, Board J, Faggiani D, et al., 2010, Model studies for the synthesis of the antibiotic lactonamycin and the discovery of new reactions and mechanisms for the construction of substituted heterocycles
Tokan WM, Schweizer S, Thies C, et al., 2009, Palladium-Catalyzed Cascade Oligocyclizations Involving Competing Elementary Steps Such as Thermal [1,5]-Acyl Shifts, HELVETICA CHIMICA ACTA, Vol: 92, Pages: 1729-1740, ISSN: 0018-019X
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