Total synthesis of (-)Quinocarcin

(34) Synthetic Studies on Quinocarcin and Its Related Compounds. 5. Synthesis and Antitumor Activity of Various Structual Types of Quinocarcin Congeners, Kato, T.; Kirihara, M.; Yoshino, T.; Tamura, T.; Ikeuchi, F.; Nakatani, K.; Matsuda, F.; Yamada, K.; Gomi, K.; Ashizawa, T.; Terashima, S. Tetrahedron 1994, 50, 6259-6270.

Asymmetric Total Synthesis of (-)-Quinocarcin

C-N Ring Construction: The Fujii/Ohno Synthesis of (-)-Quinocarcin April 22, 2013

Quinocarcin synthesis « Naturalproductman’s Blog

Transition-metal-catalyzed reactions have the potential to provide significant improvements to the syntheses of complex target molecules. These reactions can be used to achieve a variety of different atom-economical transformations and cascade reactions and, therefore, provide access to synthetic strategies that would otherwise be unavailable using classical organic chemistry. To exemplify the utility of the latest transition-metal-catalyzed reactions for the construction of important target structures, we have been involved in the total synthesis of natural products bearing widely known chemical scaffolds. In this account, we report our recent studies on the use of a palladium-catalyzed cascade cyclization reaction and a gold(I)-catalyzed hydroamination reaction for the construction of the core structures of alkaloids, as well as their application to the total syntheses of lysergic acid, lysergol, isolysergol, and quinocarcin. 1 Introduction 2 Ergot Alkaloid Synthesis 2.1 Construction of the Core Structure by Palladium-Catalyzed Cascade Cyclization 2.2 Asymmetric Total Syntheses of (+)-Lysergic Acid and ÂRelated Alkaloids 3 Quinocarcin Synthesis 3.1 Construction of the Core Structure by Gold-Catalyzed ÂHydroamination 3.2 Asymmetric Total Synthesis of (-)-Quinocarcin 4 Concluding Remarks

A total synthesis of (+,-)-quinocarcin - Rice Scholarship …

This isoquinoline-forming aryne annulation reaction is further employed in a concise asymmetric total synthesis of the tetrahydroisoquinoline antitumor antibiotic, (–)-quinocarcin. In addition to this key transformation, the synthetic route features an auxiliary-mediated diastereoselective dipolar cycloaddition to set the absolute stereochemistry and a novel two-step reduction to form the tetrahydroisoquinoline. In total, this strategy has enabled the shortest total synthesis of this important alkaloid reported to date.

Asymmetric total synthesis of (-)-quinocarcin.

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(6) Chiral Synthesis of the ABC-Ring System of Quinocarcin, Saito, S.; Tanaka, K.; Nakatani, K.; Matsuda, F.; Terashima, S. Tetrahedron Lett. 1989, 30, 7423-7426.

New Route to Anticancer Agent Quinocarcin :: …

(33) Synthetic Studies on Quinocarcin and Its Related Compounds. 2. Synthesis of Enantiomeric Pair of the ABC Ring System of Quinocarcin, Saito, S.; Tanaka, K.; Nakatani, K.; Matsuda, F.; Kato, T.; Terashima, S. Tetrahedron 1994, 50, 6209-6220.

Total Synthesis of (±)-Indolizomycin

The last decade has seen an outgrowth in the development of synthetic methodologies exploiting benzyne. The unique ability of this reactive intermediate to directly furnish ortho-difuntionalized aromatic systems first stoked interest in this research group as a possible partner in asymmetric arylation reactions. Since our initial forays, we have expanded our synthetic strategies to include bond insertions, cycloadditions, condensations, and multicomponent reactions. The first project discussed in this volume is the development of an aryne annulation strategy for constructing common, synthetically useful heterocyclic structures in a convergent manner. We have developed a convergent approach to indoles and indolines. Likewise, through an orthogonal functional group intallation upon an enamine substrate, isoquinolines, quinolines, and isoquinolones can all be accessed as well. In this manner, we have been able to generate an array of functionalized heterocycles, including some that are prohibited by traditional means of synthesis. We have also begun to understand some of the reactivity trends in this context for the elusive aryne reaction partner. The development of the aryne annulation strategy for the synthesis of isoquinolines directly led to the shortest reported total synthesis of the opiate alkaloid papaverine, and the tetrahydroisoquinoline anticancer antibiotic quinocarcin. Our more recent, ongoing efforts toward the synthesis of the bis-tetrahydroisoquinoline antitumor molecule jorumycin and its many structural relatives are detailed herein. Jorumycin has been targeted through a combination of aryne annulation and acyl-alkylation/condensation methodologies aimed at the synthesis of a functionalized bis-isoquinoline intermediate. Reduction of this key bis-isoquinoline to a bis-tetrahydroisoquinoline and subsequent lactamization will provide the pentacyclic core of jorumycin and related natural products in only three steps from simple isoquinoline building blocks. The final project described is the development of several different aryne multicomponent reactions to form novel carbo- and heterocyclic scaffolds, including iminoisobenzfurans, iminoindenones, dibenzoketocaprolactams, and 2-quinolones.