Two approaches to the synthesis of isoschizogamine were reported. Both routes utilized an efficient aza-Claisen rearrangement to establish the absolute stereochemistry of the all-carbon quaternary center in the natural product. In the first approach, a highly diastereoselective (10:1) hetero-Diels-Alder reaction was utilized to reach a densely functionalized tetrahydroquinoline derivative as an advanced intermediate to the targeted alkaloid. An acylamidine intermediate was prepared and studied in the intramolecular cyclization reaction under acidic conditions in our second approach.
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Synthetic Studies of Isoschizogamine: Alternative Preparation of the Key Intermediate.
Chem Pharm Bull (Tokyo)
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Graduate School of Pharmaceutical Sciences, Nagoya University.
An alternative synthetic route toward a key intermediate in the total synthesis of isoschizogamine is described. The Claisen-Johnson rearrangement stereoselectively constructed a quaternary carbon. Trifluoroperacetic acid mediated the Baeyer-Villiger oxidation to form a bicyclic lactone.
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Laboratory of Synthesis and Natural Products, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, EPFL-SB-ISIC-LSPN, BCH 5304, 1015 Lausanne (Switzerland) http://lspn.epfl.ch.
A concise enantioselective total synthesis of (-)-isoschizogamine, a complex bridged polycyclic monoterpene indole alkaloid, was accomplished. N-Alkylation of an enantio-enriched imine with an alkyl iodide afforded an iminium salt, which, upon heating by microwave irradiation in the presence of pivalic acid, was converted into the hexacyclic structure of natural product by a complex but ordered domino sequence. The one-pot process leading to the formation of one C-C bond and three C-N bonds created three rings and three contiguous stereogenic centers with complete control of both the relative and absolute stereochemistry.
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Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba 6-3, Aramaki, Aoba-ku, Sendai 980-8578 (Japan), Fax: (+81) 22-795-6877.
The total synthesis of (-)-isoschizogamine was accomplished, featuring the construction of the quaternary carbon center by the modified Johnson-Claisen rearrangement in basic media and the facile assembly of the key tetracyclic quinolone intermediate through a cascade cyclization. The characteristic cyclic aminal was constructed by late-stage C-H functionalization at the position adjacent to the lactam nitrogen using a combination of CrO3 and nBu4 NIO4 and subsequent Bi(OTf)3 -mediated cyclization.
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Key Laboratory of Drug Targeting and Drug Delivery Systems of the Ministry of Education, West China School of Pharmacy and State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041 (P. R. China).
Total syntheses of (-)-isoschizogamine and (-)-2-hydroxyisoschizogamine are described. The synthesis employs two asymmetric Michael additions to establish chiral centers at C7 and the quaternary carbon C20. Regioselective reduction of the methylthioiminium cation rather than the enamine generates an isoschizogamine-type pentacyclic skeleton.
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Chem Pharm Bull (Tokyo)
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Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, Japan.
Herein we present our unique strategies to synthesize natural products. To prepare mersicarpine, an atypical indole alkaloid, our procedure features an Eschenmoser-Tanabe fragmentation to synthesize an alkyne unit, a combination of a Sonogashira coupling and a gold(III) catalyzed cyclization to construct the indole skeleton, and a one-pot process to arrange the cyclic imine and the hemiaminal moieties. Additionally, we synthesized a frog poison, histrionicotoxin, via a chirality transfer from an allenylsilane to prepare a pseudosymmetrical dienyne, dienyne metathesis to produce an optically active bicyclo [5.
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