- (E)-β-borylstyrene in the diels-alder reaction with 3,5-dibromo-2-pyrone for the syntheses of (±)-1-epi-pancratistatin and (±)-pancratistatin
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New synthetic routes to (±)-1-epi-pancratistatin and (±)-pancratistatin were devised using (E)-β-borylstyrene as a dienophile for the key Diels-Alder reaction with 3,5-dibromo-2-pyrone. The boronate in the cycloadduct was oxidized to provide the pivotal C1-hydroxyl group of the titled compounds.
- Cho, Hyun-Kyu,Lim, Hwa-Yeon,Cho, Cheon-Gyu
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- ISOCARBOSTYRIL ALKALOIDS AND FUNCTIONALIZATION THEREOF
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Enantioselective total syntheses of the anticancer isocarbostyril alkaloids (+)-7-deoxypancratistatin, (+)-pancratistatin, (+)-lycoricidine, and (+)-narciclasine are described. Our strategy for accessing this unique class of natural products is based on the development of a Ni-catalyzed dearomative trans-1,2-carboamination of benzene. The effectiveness of this dearomatization approach is notable, as only two additional olefin functionalizations are needed to construct the fully decorated aminocyclitol cores of these alkaloids. Installation of the lactam ring has been achieved through several pathways and a direct interconversion between natural products was established via a late-stage C-7 cupration. Using this synthetic blueprint, we were able to produce natural products on a gram scale and provide tailored analogs with improved activity, solubility, and metabolic stability.
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Page/Page column 65; 71; 72
(2020/07/04)
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- Enantioselective Synthesis of Isocarbostyril Alkaloids and Analogs Using Catalytic Dearomative Functionalization of Benzene
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Enantioselective total syntheses of the anticancer isocarbostyril alkaloids (+)-7-deoxypancratistatin, (+)-pancratistatin, (+)-lycoricidine, and (+)-narciclasine are described. Our strategy for accessing this unique class of natural products is based on the development of a Ni-catalyzed dearomative trans-1,2-carboamination of benzene. The effectiveness of this dearomatization approach is notable, as only two additional olefin functionalizations are needed to construct the fully decorated aminocyclitol cores of these alkaloids. Installation of the lactam ring has been achieved through several pathways and a direct interconversion between natural products was established via a late-stage C-7 cupration. Using this synthetic blueprint, we were able to produce natural products on a gram scale and provide tailored analogs with improved activity, solubility, and metabolic stability.
- Bingham, Tanner W.,Hernandez, Lucas W.,Olson, Daniel G.,Svec, Riley L.,Hergenrother, Paul J.,Sarlah, David
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supporting information
p. 657 - 670
(2019/01/08)
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- METAL CATALYZED DEAROMATIVE 1,2-CARBOAMINATION
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Described herein is the development of an arenophile-mediated, nickel-catalyzed dearomative trans-1,2-carboamination protocol. A range of readily available aromatic compounds was converted to the corresponding dienes using Grignard reagents as nucleophiles. This strategy provided products with exclusive trans-selectivity and high enantioselectivity was observed in case of benzene and naphthalene. The utility of this methodology was showcased by controlled and stereoselective preparation of small, functionalized molecules. A concise synthesis of (+)-pancratistatin and (+)-7-deoxypancratistatin from benzene using an enantioselective, dearomative carboamination strategy has been achieved. This approach, in combination with the judicious choice of subsequent olefin-type difunctionalization reactions, permits rapid and controlled access to a hexasubstituted core. Finally, minimal use of intermediary steps as well as direct, late stage C-7 hydroxylation provides both natural products in six and seven operations.
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- Synthesis of (+)-Pancratistatins via Catalytic Desymmetrization of Benzene
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A concise synthesis of (+)-pancratistatin and (+)-7-deoxypancratistatin from benzene using an enantioselective, dearomative carboamination strategy has been achieved. This approach, in combination with the judicious choice of subsequent olefin-type difunctionalization reactions, permits rapid and controlled access to a hexasubstituted core. Finally, minimal use of intermediary steps as well as direct, late stage C-7 hydroxylation provides both natural products in six and seven operations.
- Hernandez, Lucas W.,Pospech, Jola,Kl?ckner, Ulrich,Bingham, Tanner W.,Sarlah, David
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p. 15656 - 15659
(2017/11/14)
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- Total Synthesis of (+)-Pancratistatin by the Rh(III)-Catalyzed Addition of a Densely Functionalized Benzamide to a Sugar-Derived Nitroalkene
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Herein, we report the concise total synthesis of (+)-pancratistatin, accessed in a 10-step linear sequence from commercially available inputs. The convergent synthesis features a highly diastereoselective Rh(III)-catalyzed C-H bond addition to a d-glucose
- Potter, Tyler J.,Ellman, Jonathan A.
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p. 2985 - 2988
(2017/06/07)
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- Enantioselective synthesis of protected nitrocyclohexitols with five stereocenters. Total synthesis of (+)-pancratistatin
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2-Methoxymethylpyrrolidine best performed, among several other proline derivatives, to control the enantioselective [3+3] annulation of β-(hetero)aryl-α-nitro-α,β-enals with commercial 2,2-dimethyl-1,3-dioxan-5-one, a procedure that renders highly oxygenated nitrocyclohexanes endowed with five new stereocenters. Use of this reaction allowed the development of a total synthesis of the antitumoral natural product (+)-pancratistatin; it also converted our previous racemic route to tetrodotoxin into an enantioselective one.
- Cagide-Fagín, Fernando,Nieto-García, Olaia,Lago-Santomé, Hugo,Alonso, Ricardo
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p. 11377 - 11382
(2013/02/23)
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- β-silyl styrene as a dienophile in the cycloaddition with 3,5-dibromo-2-pyrone for the total synthesis of (±)-pancratistatin
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A new synthetic route to (±)-pancratistatin was devised utilizing β-silyl styrene as a dienophile in the cycloaddition with 3,5-dibromo-2-pyrone. The TMS group incorporated in the cycloadduct permitted a facile elimination process for the eventual install
- Jung, Yong-Geun,Kang, Ho-Ung,Cho, Hyun-Kyu,Cho, Cheon-Gyu
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p. 5890 - 5892
(2011/12/15)
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- PROCESSES FOR THE PREPARATION OF PANCRATISTATIN AND PANCRATISTATIN ANALOGUES
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Processes for the preparation of pancratistatin and pancratistatin analogues. The key step is the reaction of a 1,3-dioxan-5-one and a nitroolefine in the presence of an amine. The process may take place in an enantioselective way when a chiral amine is u
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Page/Page column 54
(2009/04/25)
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- Convergent synthesis of pancratistatin from piperonal and xylose
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A synthesis of the antitumour agent pancratistatin is described from piperonal and D-xylose. Piperonal is converted into cinnamyl bromide 11 while methyl 5-iodoribofuranoside 12 is derived from xylose, The allylic bromide and the iodocarbohydrate are combined in a zinc-mediated tandem reaction to afford a highly functionalised 1,7-diene, which is then converted into the corresponding cyclohexene by ring-closing olefin metathesis. Subsequent Overman rearrangement, dihydroxylation and deprotection afford the natural product in a total of 25 steps from, the two starting materials. The longest linear sequence is from piperonal and gives rise to pancratistatin in 18 steps and 7.0% overall yield. Wiley-VCH Verlag GmbH & Co. KGaA.
- Dam, Johan Hygum,Madsen, Robert
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experimental part
p. 4666 - 4673
(2009/12/05)
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- Antineoplastic agents. 550. Synthesis of 10b(S)-epipancratistatin from (+)-narciclasine
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By means of a five-step reaction sequence, narciclasine (2a), isolated from Narcissus sp., was converted to 10b(S)-epipancratistatin (3a) in 5.7% overall yield. The key step entailed a radical-initiated 10b,1 C-O cleavage employing tributyltin hydride to yield a B/C cis ring juncture (3b). Biological evaluation of 10b(S)-epipancratistatin (3a) provided evidence that antineoplastic activity was reduced by a factor of 10 when the B/C trans juncture was replaced with a B/C cis ring juncture.
- Pettit, George R.,Melody, Noeleen,Herald, Delbert L.,Knight, John C.,Chapuis, Jean-Charles
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p. 417 - 422
(2008/02/04)
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- A concise synthesis of (+)-pancratistatin using pinitol as a chiral building block
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A concise approach toward (+)-Pancratistatin has been achieved via 12 steps from pinitol. An ultrasound assisted arylcerium induced ring opening of cyclic sulfate was employed as a key step.
- Li, Min,Wu, Anmei,Zhou, Peijie
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p. 3707 - 3710
(2007/10/03)
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- Total Synthesis of Pancratistatin Relying on the [3,3]-Sigmatropic Rearrangement
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A new total synthesis of the antitumor alkaloid, pancratistatin (1), has been accomplished from readily available starting materials. Claisen rearrangement of the racemic dihydropyranethylene 17 was employed to construct the A and C rings with the appropr
- Ko, Hyojin,Kim, Eunkyung,Park, Jae Eun,Kim, Deukjoon,Kim, Sanghee
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p. 112 - 121
(2007/10/03)
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- Stereocontrolled Total Synthesis of Pancratistatin
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(Matrix Presented) A new total synthesis of the antitumor alkaloids, pancratistatin (1), has been accomplished from readily available staring materials. The Claisen rearrangement of dihydropyranethylene 5 was employed to construct the A and C rings. Stere
- Kim, Sanghee,Ko, Hyojin,Kim, Eunkyung,Kim, Deukjoon
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p. 1343 - 1345
(2007/10/03)
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- Antineoplastic agents. 450. Synthesis of (+)-pancratistatin from (+)-narciclasine as relay
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(+)-Narciclasine (2) available in quantity from certain Amaryllidaceae species or by total synthesis was employed as a precursor for a 10-step synthetic conversion (3.6% overall yield) to natural (+)-pancratistatin (1a). The key procedures involved epoxidation of natural (+)-narciclasine (2) to epoxide 6, reduction to diol 8, and formation of cyclic sulfate 12 and its ring opening with cesium benzoate followed by saponification of the benzoate to afford (+)-pancratistatin (1a).
- Pettit,Melody,Herald
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p. 2583 - 2587
(2007/10/03)
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- Studies on the narciclasine alkaloids: Total synthesis of (+)- narciclasine and (+)-pancratistatin
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Enantioselective total syntheses of the antimmor alkaloids, (+)- narciclasine and (+)-pancratistatin, are reported. These syntheses feature a stereo- and regiocontrolled aryl enamide photocyclization to construct a common, advanced intermediate possessing a transfused BC substructure. Differential functional group interchange in the C-ring of this phenanthridone core structure allows for the production of the two target natural products in enantiomerically pure form.
- Rigby, James H.,Maharoof, Umar S. M.,Mateo, Mary E.
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p. 6624 - 6628
(2007/10/03)
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- Application of the β-azidonation reaction to the synthesis of the antitumor alkaloid (+)-pancratistatin
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o-Vanillin 21 was converted into 24 following literature procedures. Treatment of 24 with n-BuLi/THF followed by addition of 25 gave 26. Dehydration (POCL3/pyridine/DBU), hydrogenation and hydrolysis of 26 gave the ketone 29. Chirality was introduced by deprotonation of 29 with the lithium salt of (+)-bis(αmethylbenzyl)amine, followed by triisopropylsilyl trifluoromethanesulfonate to give 30 (95%). β-Azidonation of 30 with (PhiO)n/TMSN3 rapidly produced 31 (95%) as a mixture of trans- and cis- diastereomers in a 3.5:1 ratio. Reduction with LiAIH4 followed by methyl chloroformate/pyridine gave 32, which on treatment with MCPBA/CH2CL2/imidazole resulted in 33. Hydrolysis of 33 gave 34, which when exposed to KOBu(t)/HMPA at 90 °C resulted in 39. After conversion of 39 into enone 42, epoxidation with NaHCO3/H2O2/MeOH gave 43. Reduction of 43 with L-selectride followed by solvolysis with sodium benzoate in water gave 46, which was immediately acetylated to give 47. Lactam formation (Tf2O/DMAP) converted 47 into 48 and the regioisomer 49 (7:1). The mixture of 48 and 49 demethylated to give 50 and the acetate protecting groups removed to give (+)pancratistatin 1.
- Magnus, Philip,Sebhat, Iyassu K.
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p. 15509 - 15524
(2007/10/03)
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- Toluene dioxygenase-mediated cis-dihydroxylation of aromatics in enantioselective synthesis. Asymmetric total syntheses of pancratistatin and 7-deoxypancratistatin, promising antitumor agents
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Whole-cell biooxidation of bromobenzene with Pseudomonas putida 39D or the recombinant Escherichia coli JM109 (pDTG601) yields (1S,2S)-3-bromocyclohexa-3,5-diene-1,2-diol (9a), which is protected as the acetonide and converted to vinylaziridines 7, 15a, 6
- Hudlicky, Tomas,Tian, Xinrong,K?nigsberger, Kurt,Maurya, Rakesh,Rouden, Jacques,Fan, Boreas
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p. 10752 - 10765
(2007/10/03)
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- Total synthesis of (±)-pancratistatin
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The total synthesis of the antitumor title compound has been accomplished. Among the key steps was an iodolactonization of a cyclohexadiene bearing a neighboring carboxamido group mediated by an ortho-stannylated phenol. A series of cis vicinal functional
- Danishefsky,Lee
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p. 4829 - 4837
(2007/10/02)
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