The Application of Asymmetric Allylstannane Additions Towards the Total Synthesis of ( - )-colletol and Synthetic Studies Towards (+)-7- Deoxypancratistatin PDF Download
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Author: Jerry Anthony Murry
Publisher:
ISBN:
Category : Aldehydes
Languages : en
Pages : 260
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Author: Jerry Anthony Murry
Publisher:
ISBN:
Category : Aldehydes
Languages : en
Pages : 260
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Author:
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ISBN:
Category : Dissertations, Academic
Languages : en
Pages : 912
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Author:
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ISBN:
Category : Dissertation abstracts
Languages : en
Pages : 704
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Author: Merritt Brooks Andrus
Publisher:
ISBN:
Category : Aldehydes
Languages : en
Pages : 500
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Author: Ruowei Mo
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Two efficient, regio- and stereo controlled synthetic approaches to the synthesis of racemic analogs of pancratistatin have been accomplished and they serve as the model systems for the total synthesis of optically active 7-deoxy-pancratistatin. In the Diels-Alder approach, an efficient [4+2] cycloaddition of 3,4-methylenedioxyco- nitrostyrene with Danishefsky's diene to selectively form an exo-nitro adduct has been developed as the key step in the construction of the C-ring of the target molecule. In the Michael addition approach, the key step was a conjugate addition of an organic zinc-cuprate to the 3,4-methylenedioxy-(B-nitrostyrene, followed by a diastereocontroUed closure to form the cyclohexane C-ring of the target molecule via an intramolecular nitro-aldol cyclization on a neutral alumina surface. A chair-like transition state for such a cyclization has been established and such a chelation controlled transition state can be useful in the prediction of diastereoselectivity in other related 6-exo-trig nitroaldol reactions. Cyclization of the above products fi^om both approaches by using a Bischler-Napieralski type reaction afforded two lycoricidine derivatives 38 and 50 in good yields. The initial results from the above modeling studies as well as the analysis of the synthetic strategy were directed to a chiral pool approach to the total synthesis of optically active 7-deoxy-pancratistatin. Selective monsilylation and iodination of Ltartaric acid provided a chiral precursor for the proposed key Michael transformation. The outlook for the total synthesis of 7-deoxy-pancratistatin by this approach is very promising.A concise synthesis of novel designed, optically pure, Cz-symmetrical disulfonylamide chiral ligands starting from L-tartaric acid has also been achieved. This sequence employs the metallation of indole followed by Sfj2 replacement of a dimesylate as the key step. The activity for this Cz-symmetric chiral disulfonamide ligand in the catalytic enantioselective reaction has been confirmed by nucleophilic addition to benzaldehyde in the disulfonamide-Ti (0-i-Pr)4-diethylzinc system with a 48% yield and a 33% e.e. value. Such a ligand tethered with a suitable metal complex should be also applicable towards the total synthesis of 7-deoxy-pancratistatin.
Author: Stuart Edward Bradley
Publisher:
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Category :
Languages : en
Pages :
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![Asymmetric Aldol Additions Using Titanium Enolates of Acylthiazolidinethiones [microform] : Application Towards the Total Synthesis of Apoptolidinone PDF](https://books.google.com/books/content/images/frontcover/TWf5tgAACAAJ?fife=w80-h100)
Author: Chaudhary, Kleem
Publisher: Ann Arbor, Mich. : University Microfilms International
ISBN:
Category : Aldol condensation
Languages : en
Pages : 458
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Author: Maksim Osipov
Publisher:
ISBN:
Category :
Languages : en
Pages :
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This dissertation deals with the development of metal-catalyzed asymmetric allylic alklyations, and their use for the synthesis of alkaloids and other nitrogen-containing biologically active compounds. The synthesis of the drug ( -- )-ranirestat is disclosed, which relies on a Pd-catalyzed asymmetric allylic alkylation (Pd-AAA) as a key step. The development and application of pyrroles and indoles as nucleophiles in the Pd-AAA is described. A Pd-catalyzed decarboxylative asymmetric alkylation approach to constructing vicinal all-carbon quaternary stereocenters is disclosed, and this methodology is used to complete the formal synthesis of several cyclotryptamine alkaloids. Finally, a catalytic asymmetric total synthesis of the alkaloid ( -- )-perophoramidine and efforts towards the alkaloid communesin B are described. Both syntheses employ a molybdenum-catalyzed asymmetric allylic alkylation as a key asymmetric step. ( -- )-Ranirestat is a potent aldose reductase inhibitor currently in phase III clinical testing for its ability to treat diabetic neuropathy. We have developed a concise, catalytic asymmetric total synthesis of ( -- )-ranirestat, which was completed in 8 steps and 14% overall yield starting from inexpensive, commercially available 2-(trichloroacetyl)pyrrole. A palladium-catalyzed asymmetric allylic alkylation (Pd-AAA) of an imidomalonate and an allylic carbonate serve as a key transformation to construct the tetrasubstituted stereocenter in the target with high yield and enantioselectivity. Protiodesilylation followed by oxidative cleavage of the allyl moiety and cyclization are used to access ( -- )-ranirestat. Nitrogen heterocycles are found in a variety of natural products and other biologically active compounds. We have demonstrated that pyrroles and indoles bearing electron-withdrawing groups are competent nucleophiles in the Pd-AAA with vinyl aziridines. The resulting alkylated products were obtained with high levels of regio-, chemo-, and enantioselectivity. Both substituted 1H-pyrroles and 1H-indoles were successfully employed to give exclusively the branched N-alkylated products. The synthetic utility of this asymmetric process was demonstrated through the elaboration of pyrrole products into bromopyrrole alkaloids longamide B, longamide B methyl ester, hanishin, agesamides A and B, and cyclooroidin. Likewise, the synthetic utility of the indole products was demonstrated by elaboration into several patented piperazinones and piperazine medicinal chemistry lead compounds. 1H-Pyrroles have also shown to serve as nucleophiles with meso electrophiles in the Pd-AAA. The products from this transformation were obtained as a single regio- and diastereomer in high yield and % ee. To demonstrate synthetic utility, a pyrrole-substituted nucleoside analogue was synthesized employing this methodology as the asymmetric step. Quaternary all-carbon stereocenters are present in many natural products and biologically active compounds. The presence of this structural element greatly complicates the asymmetric assembly of molecules due to steric congestion. The asymmetric assembly is complicated further when a second vicinal, quaternary center is present in a molecular target. We have discovered that a two-fold Pd-DAAA of an oxindole-derived dienol carbonate can be used to construct two vicinal all carbon quaternary stereocenters in a diastereo- and enantioselective fashion. To demonstrate the synthetic utility of this process, the product of this transformation was used to complete the formal syntheses of the cyclotryptamine alkaloids ( -- )-chimonanthine, (+)-calycanthine ( -- )-folicanthine, and ditryptophenaline. Mechanistic investigations have suggested that the two-fold Pd-catalyzed transformation proceeds through an unusual matched and mismatched allylation to deliver the desired product. Perophoramidine was isolated from the ascidian organism Perophora namei and displays cytotoxicity toward the HCT116 colon carcinoma cell line with an IC50 of 60 æM. The complex polycyclic cage-like core of this alkaloid makes it a challenging and interesting target for total synthesis. A catalytic asymmetric total synthesis of ( -- )-perophoramidine was developed employing a molybdenum-catalyzed asymmetric allylic alkylation between an allylic phosphate and an alkyl oxindole as an asymmetric step. This key transformation provides a chiral oxindole product in high yield and with high levels of regio-, diastereo-, and enantioselectivity. The chiral oxindole product, which contains the key quaternary stereocenter present in perophoramidine, was further elaborated to a pentacyclic imino ether using a reductive cyclization, oxidative cleavage and lactamization as key transformations. The imino ether was alkylated with allyl iodide to construct the second vicinal quaternary stereocenter providing an allyl imino ether as a single regio- and diastereomer. The allyl imino ether was converted to an aldehyde via ozonolysis, which was subjected to a reductive amination and cyclization sequence to complete ( -- )-perophoramidine.
Author: Koudi Zhu
Publisher:
ISBN:
Category : Alkaloids
Languages : en
Pages : 74
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Lyconadin A is an alkaloid possessing a unique structure and antitumor activity. The total synthesis of Lyconadin A was proposed via an acyl radical cascade reaction. To investigate the possibility and stereoselectivity of the cascade cyclization, phenyl selenoester 16 was chosen as a model substrate to study the 7-exo-5-exo radical cyclization. A synthetic route to phenyl selenoester 16 was developed. The 7-exo-5-exo radical cyclization was found to occur with a high yield and excellent stereoselectivty. Attempts were also tried to synthesize another radical precursor 14 albeit with less success. A synthetic pathway to the synthesis of 14 as well as its potential use in the context of the synthesis of Lyconadin A was proposed.
Author: Vincent Poral
Publisher:
ISBN:
Category : Enantioselective catalysis
Languages : en
Pages : 267
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