Total Synthesis of the Quinone Epoxide Dimer (+)-Torreyanic Acid:  Application of a Biomimetic Oxidation/Electrocyclization/Diels−Alder Dimerization Cascade<sup>1</sup>

Li, Chaomin; Johnson, Richard P.; Porco, John A.

doi:10.1021/ja021396c

Cited by 151 publications

(112 citation statements)

References 57 publications

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“…(37). [64] 37 Several chemoselective oxidations of alcohols with 2 have been used in recent natural product syntheses. Selective oxidation of the C35 alcohol of 55 in the presence of the diol moiety with DMP afforded MOMprotected TMC-95A 56, a potent proteasome inhibitor, in 80% yield, Eq.…”

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confidence: 99%

Hypervalent Iodine Reagents for the Oxidation of Alcohols and Their Application to Complex Molecule Synthesis

2004

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Hypervalent iodine(V) derivatives such as 2-iodoxybenzoic acid (IBX) and Dess±Martin periodinane [DMP; 1,1,1-tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3-(1H)-one] have been used widely for the oxidation of alcohols to aldehydes and ketones during the last decade because of their high chemoselectivity, mild reactivity, and high yielding process. This review focuses on the recent progress in the oxidation of alcohols to carbonyl compounds using IBX, DMP, and other hypervalent iodine reagents, and their application to total syntheses of a variety of complex natural products.

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confidence: 99%

Hypervalent Iodine Reagents for the Oxidation of Alcohols and Their Application to Complex Molecule Synthesis

2004

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“…[8][9][10][11]. With several electrophilic sites and a high degree of unsaturation, 3 was perceived to be a challenging objective for synthesis, and we elected to explore the possibility of producing this potentially transient intermediate in situ from a doubly activated, polyunsaturated acyclic compound of type 1.…”

mentioning

confidence: 99%

A nucleophile-catalyzed cycloisomerization permits a concise synthesis of (+)-harziphilone

Stark

Pekari

Sorensen

2004

Proc. Natl. Acad. Sci. U.S.A.

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Substantial structural transformations of much use in complex chemical synthesis can be achieved by channeling the reactivity of highly unsaturated molecules. This report describes the direct conversion of an acyclic polyunsaturated diketone to the HIV-1 Rev͞Rev-responsive element inhibitor harziphilone under mild reaction conditions. nucleophilic catalysis ͉ Baylis-Hillman reaction ͉ conjugate additions ͉ electrocyclizations ͉ domino reactions T he reactivity of activated polyenes is the basis for some of the most impressive structural transformations in nature and chemical synthesis. The biosyntheses of the complex structures of the polycyclic triterpenes from squalene and 2,3-oxidosqualene may be viewed as paragons for processes that build polycyclic molecular complexity directly from reactive polyenes (1-3). In connection with our efforts to channel the reactivity of activated polyunsaturated molecules, we sought mild reaction conditions under which compound 1 could be isomerized to the bicyclic structure of harziphilone (2), a naturally occurring inhibitor of the binding interaction between the HIV-1 Rev protein and the Rev-responsive element (RRE) of viral mRNA (4) (Scheme 1). This report describes an enantioselective synthesis of (ϩ)-harziphilone based on the general idea expressed in Scheme 1.The structure of (ϩ)-harziphilone (2) comprises fifteen carbon atoms, two six-membered ring systems, one carbocyclic and the other heterocyclic, a keto group, two contiguous hydroxylbearing stereocenters, and a pentadienyl side chain. All of the polar groupings of harziphilone are confined to the sixmembered carbocycle, whereas the hydrophobic pentadienyl moiety is displayed as a side chain on the ␣-pyran ring. Our approach to the problem of synthesizing this natural product was guided by the retrosynthetic analysis shown in Scheme 2.The independent early investigations of Büchi (5) and Marvell (6, 7) provided a sound basis for the proposal that the oxacyclic ring of harziphilone, with its particular arrangement of alkenes, could arise by a 6 -electrocyclization of a compound of type 3 (for selected examples of this type of valence isomerization in synthesis see refs. 8-11). With several electrophilic sites and a high degree of unsaturation, 3 was perceived to be a challenging objective for synthesis, and we elected to explore the possibility of producing this potentially transient intermediate in situ from a doubly activated, polyunsaturated acyclic compound of type 1. To implement this concept, we would seek a suitable heteroatom nucleophile that could attack the unsubstituted enone moiety in 1. Although almost certainly reversible, such a site-selective, intermolecular conjugate addition reaction could trigger an intramolecular conjugate addition (see arrows in 4), resulting in the production of a key carbon-carbon bond and the carbocyclic ring of (ϩ)-harziphilone (for selected tandem conjugate addition͞Michael cyclization reactions see refs. 12-17). A ␤-elimination of the heteroatom nucleophile might then genera...

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“…Da die asymmetrische Sharpless-Epoxidierung [101] dieses Epoxid nur in 85 % Ausbeute und mit 70 % ee lieferte, wurde nach einem besseren Verfahren gesucht. Eine tartrat- vermittelte asymmetrische nucleophile Epoxidierung [102] lieferte schließlich das gewünschte Epoxid in 94 % Ausbeute und mit 90 % ee. Das Epoxid 171 wurde dann mit einer Sequenz aus Standardreaktionen zum Vinylbromid 172 umgesetzt.…”

Section: Kinamycin Cunclassified

Fortschritte in der Chemie und Biologie natürlicher Antibiotika

et al. 2009

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Seit der bahnbrechenden Entdeckung von Penicillin wurde die Vielfalt natürlich vorkommender Moleküle ausgiebig hinsichtlich ihrer Eignung als Medikamente sowie zum Auffinden neuer Leitstrukturen beim Wirkstoffdesign untersucht. Die Suche nach Wirkstoffen, mit denen Infektionskrankheiten bekämpft werden können, war dabei von besonderem Interesse und verlief sehr erfolgreich. Die Erforschung der Antibiotika weist eindrucksvolle Entdeckungen und Geschichten über die Entwicklung von Wirkstoffen auf, von denen die große Mehrheit ihren Ursprung in Naturstoffen hat. Die Chemie und besonders die chemische Synthese haben eine bedeutende Rolle dabei gespielt, natürlich vorkommende Antibiotika und deren Derivate für die medizinische Anwendung bereitzustellen, und zweifellos werden diese Disziplinen auch künftig Schlüsseltechnologien sein. In dieser Übersicht stellen wir einige der bedeutendsten neueren Entwicklungen und Fortschritte in der Chemie, Biologie und Medizin natürlich vorkommender Antibiotika vor, wobei die Totalsynthese, das Design von Analoga und die biologische Bewertung von Molekülen mit neuartigen Wirkmechanismen im Vordergrund stehen.

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Total Synthesis of the Quinone Epoxide Dimer (+)-Torreyanic Acid: Application of a Biomimetic Oxidation/Electrocyclization/Diels−Alder Dimerization Cascade¹

Cited by 151 publications

References 57 publications

Hypervalent Iodine Reagents for the Oxidation of Alcohols and Their Application to Complex Molecule Synthesis

Hypervalent Iodine Reagents for the Oxidation of Alcohols and Their Application to Complex Molecule Synthesis

A nucleophile-catalyzed cycloisomerization permits a concise synthesis of (+)-harziphilone

Fortschritte in der Chemie und Biologie natürlicher Antibiotika

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Total Synthesis of the Quinone Epoxide Dimer (+)-Torreyanic Acid: Application of a Biomimetic Oxidation/Electrocyclization/Diels−Alder Dimerization Cascade1

Cited by 151 publications

References 57 publications

Hypervalent Iodine Reagents for the Oxidation of Alcohols and Their Application to Complex Molecule Synthesis

Hypervalent Iodine Reagents for the Oxidation of Alcohols and Their Application to Complex Molecule Synthesis

A nucleophile-catalyzed cycloisomerization permits a concise synthesis of (+)-harziphilone

Fortschritte in der Chemie und Biologie natürlicher Antibiotika

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Total Synthesis of the Quinone Epoxide Dimer (+)-Torreyanic Acid: Application of a Biomimetic Oxidation/Electrocyclization/Diels−Alder Dimerization Cascade¹