Indoles. V. Syntheses and reactions of cycloalkanon[c,d]indole derivatives.

Nagasaka, Tatsuo; Ohki, Sadao

doi:10.1248/cpb.25.3023

Cited by 29 publications

(7 citation statements)

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“…In presence of H 2 SO 4 , the oxime derivative of 1d gave a complex mixture of products, and 1e was difficult to isolate. It was assumed that H 2 SO 4 gave both the desired and undesired products due to alkyl and aryl migration trans to nitrogen . Instead heating the oxime derivative of 1d with SOCl 2 gave the desired 1e as the sole product in moderate 40% yield along with black tar.…”

Section: Results and Discussionmentioning

confidence: 99%

“…It was assumed that H 2 SO 4 gave both the desired and undesired products due to alkyl and aryl migration trans to nitrogen. 20 Instead heating the oxime derivative of 1d with SOCl 2 gave the desired 1e as the sole product in moderate 40% yield along with black tar. The formation of 1e was confirmed by the coupling between amide proton and adjacent −CH 2 group protons ( 1 H COSY NMR).…”

Section: ■ Introductionmentioning

confidence: 99%

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Poly(ADP-ribose) Polymerase in Neurodegeneration: Radiosynthesis and Radioligand Binding in ARC-SWE tg Mice

Alluri

Riss

2018

ACS Chem. Neurosci.

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We report the synthesis, radiosynthesis, and characterization of a radioligand for poly(ADP-ribose) polymerase (PARP). PARP is of central importance in cell homeostasis, neuroplasticity, and neurodegeneration in the brain. A radiolabeled PARP inhibitor was developed and used for autoradiographic quantification of PARP protein concentration in wild-type and transgenic rodent brains ex vivo in high resolution. The binding of [H]rucaparib was found to be confined to PARP-expressing domains, for example, cerebellar cortex or hippocampal regions in both models. Saturation binding experiments confirmed selective and reversible binding to a single site ( K = 1.1 ± 0.2 nM).

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Section: Results and Discussionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Poly(ADP-ribose) Polymerase in Neurodegeneration: Radiosynthesis and Radioligand Binding in ARC-SWE tg Mice

Alluri

Riss

2018

ACS Chem. Neurosci.

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“…In 1994, Goto and co-workers 21 reported the synthesis of 1 from 2-unsubstituted N-protected 3-(indol-3-yl)propionic acid (54) (Scheme 8). The direct cyclization of 53 and its N-acetyl derivatives had been studied previously by Nagasaka and Ohki, 19 but they obtained only cyclization products at the 2-position. Goto and co-workers observed that the nucleophilicity of the pyrrole ring could be decreased by the use of a strong electron acceptor and a bulky N-pivaloyl group.…”

Section: Disconnection A: Cyclization Reaction Of the Opportune 34-dmentioning

confidence: 99%

“…In 1977, Uhle's ketone (1) was synthesized by Friedel-Crafts cyclization of 2-substituted indole-3-propanoic acids (Scheme 6). 19 In fact, attempts of intramolecular Friedel-Crafts cyclization on 2-unsubstituted derivatives gave only the Friedel-Crafts reaction at the 2-position. Fischer indolization of phenylhydrazone derivatives 38 and 39, obtained from the corresponding benzenediazonium salts of 36 and 37, respectively, and ethyl 2-oxocyclopentanecarboxylate (12), gave the 2,3-disubstituted indoles 40 and 41, which were derivatized to the acid chlorides and submitted to the Friedel-Crafts reaction with AlCl 3 in 1,2-dichloroethane to produce 42 and 43, respectively.…”

Section: Short Review Synthesismentioning

confidence: 99%

Synthesis and Reactivity of Uhle’s Ketone and Its Derivatives

Bartoccini¹,

Piersanti²

2020

Synthesis

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Uhle’s ketone and its derivatives are highly versatile intermediates for the synthesis of a variety of 3,4-fused tricyclic indole frameworks, i.e. indole alkaloids of the ergot family, that are found in various bioactive natural products and pharmaceuticals. Therefore, the development of a convenient preparative method for this structural motif as well as its opportune/useful derivatization have been the subject of longstanding interest in the fields of synthetic organic chemistry and medicinal chemistry. Herein, we summarize recent and less recent methods for the preparation of Uhle’s ketone and its derivatives as well as its main reactivity towards the synthesis of bioactive substances. Regarding the preparation, it can be roughly classified into two categories: (a) using 4-unfunctionalized and 4-functionalized indole derivatives as starting materials to construct a fused six-member ring, and (b) constructing the indole ring through intramolecular cycloaddition. Principally, the reactivity of the cyclic Uhle’s ketone shown here is derived from the classical electrophilicity of the carbonyl carbon or the acidity of the α-hydrogen and, though less intensively investigated, chemical reactions that induce ring expansion to form novel ring skeletons.1 Introduction2 Synthesis2.1 Disconnection A: Cyclization Reaction of the Opportune 3,4-Disubstituted Indole2.2 Disconnection B: Intramolecular Friedel–Crafts Cyclization2.3 Disconnection B: Intramolecular Cyclization via Metal–Halogen Exchange2.4 Disconnection C: Intramolecular Diels–Alder Furan Cycloaddition2.5 Disconnection D: Intramolecular Dearomatizing [3 + 2] Annulation3 Reactivity3.1 Use of Uhle’s Ketone for Lysergic Acid3.2 Use of Uhle’s Ketone for Rearranged Clavines3.3 Use of Uhle’s Ketone for Medicinal Chemistry4 Conclusion and Outlook

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“…1988, 3, 273 Benzamides 8a-c were prepared (Scheme I) by standard procedures from the appropriate acid chlorides (9) and endo-tropaneamine (10). 10 The benzotriazinones (lla-c) (Scheme II) and (12a) were prepared by nucleophilic ring opening of an appropriate isatoic anhydride by the appropriate amine* 11 followed by diazotization and neutralization.12 Yields of the intermediate anthranilamides were only moderate as attack at the 2-carbonyl appears to be more favored for more hindered amines.11 7-Amino compounds lid and 12b were prepared from 7-nitro compounds 11c and 12a, respectively, by hydrogenation over Raney nickel. In a similar manner quinazoline 13 was prepared from the anthranilamide by cyclization with triethyl orthoformate followed by hydrogenation.…”

mentioning

confidence: 99%