19283-70-6Relevant academic research and scientific papers
Synthetic studies towards the penicisulfuranols: Synthesis of an advanced spirocyclic diketopiperazine intermediate
Gayler, Kevin M.,Lambert, Kyle M.,Wood, John L.
, p. 3154 - 3159 (2019)
The 2,5-diketopiperazine (DKP) moiety is a core feature of many natural products and medicinally relevant scaffolds. As part of our efforts directed towards a total synthesis of penicisulfuranol B, we have developed and report herein: (1) the preparation of an N-hydroxy diketopiperazine intermediate accessible via a molybdenum-mediated oxidation of a parent diketopiperazine, and (2) further synthetic studies leading to a novel spirocyclic dihydrobenzofuran-containing diketopiperazine.
Unintended Formation of a 26-Membered Cycle in the Course of a Novel Approach to Myricanol, a Strained [7,0]-Metacyclophane
Chiummiento, Lucia,Choppin, Sabine,Colobert, Fran?oise,Hanquet, Gilles,Massé, Paul
, p. 559 - 564 (2020)
A convergent approach for the synthesis of (±)-myricanol, a strained diarylheptanoid isolated from Myricacae, was undertaken using a Suzuki-Miyaura coupling followed by a ring-closing metathesis (RCM). Herein, we report the unintentional formation of a 26-membered macrocycle as RCM product resulting from a head-to-tail dimerization of the seco -precursor, even in relay ring-closing metathesis (RRCM) conditions.
Synthetic studies on naturally occurring coumarins. I. A convenient synthesis of 5,8-dimethoxy- and 7,8-dimethoxycoumarins
Ishii,Kenmotsu,Dopke,Harayama
, p. 1770 - 1772 (1992)
The coumarin isolated from Artemisia carvifolia Wall was proved synthetically to be 7,8-dimethoxycoumarin and not 5,8-dimethoxycoumarin as previously proposed. 3,4-Dimethoxy- and 3,6-dimethoxysalicylaldehydes gave the corresponding coumarins in good yield by the method using phosphorane reagent in N,N-diethylaniline under reflux.
Discovery, optimization, and target identification of novel coumarin derivatives as HIV-1 reverse transcriptase-associated ribonuclease H inhibitors
De Clercq, Erik,Feng, Da,Kang, Dongwei,Liu, Xinyong,Pannecouque, Christophe,Sun, Lin,Tao, Yucen,Wei, Fenju,Zhan, Peng,álvarez, Mar,Frutos-Beltrán, Estrella,Menéndez-Arias, Luis,Urhan, ?agil
supporting information, (2021/08/19)
Despite significant advances in antiretroviral therapy, acquired immunodeficiency syndrome remains as one of the leading causes of death worldwide. New antiretroviral drugs combined with updated treatment strategies are needed to improve convenience, tolerability, safety, and antiviral efficacy of available therapies. In this work, a focused library of coumarin derivatives was exploited by cell phenotypic screening to discover novel inhibitors of HIV-1 replication. Five compounds (DW-3, DW-4, DW-11, DW-25 and DW-31) showed moderate activity against wild-type and drug-resistant strains of HIV-1 (IIIB and RES056). Four of those molecules were identified as inhibitors of the viral RT-associated RNase H. Structural modification of the most potent DW-3 and DW-4 led to the discovery of compound 8a. This molecule showed increased potency against wild-type HIV-1 strain (EC50 = 3.94 ± 0.22 μM) and retained activity against a panel of mutant strains, showing EC50 values ranging from 5.62 μM to 202 μM. In enzymatic assays, 8a was found to inhibit the viral RNase H with an IC50 of 12.3 μM. Molecular docking studies revealed that 8a could adopt a binding mode similar to that previously reported for other active site HIV-1 RNase H inhibitors.
Synthesis and evaluation of methoxy substituted 2-benzoyl-1-benzofuran derivatives as lead compounds for the development adenosine A1 and/or A2A receptor antagonists
Aucamp, Janine,Janse van Rensburg, Helena D.,Legoabe, Lesetja J.,Terre'Blanche, Gisella
, (2019/12/25)
A series of fourteen methoxy substituted 2-benzoyl-1-benzofuran derivatives were synthesised and their affinities determined for adenosine A1 and A2A receptors via radioligand binding assays to establish the structure activity relationships pertinent for A1 and A2A affinity. Compound 3j (6,7-dimethoxybenzofuran-2-yl)(3-methoxyphenyl)methanone exhibited A1 affinity (A1Ki (rat) = 6.880 μM) as well as A2A affinity (A2AKi (rat) = 0.5161 μM). Compounds 3a–b & 3i–k exhibited selective affinity towards A1 with Ki values below 10 μM. The results indicate that C6,7-diOCH3 substitution on ring A in combination with meta (C3′)–OCH3 substitution on ring B is beneficial for A1 and A2A affinity and activity. Compounds 3a–b & 3j–k showed low cytotoxicity. Upon in vitro and in silico evaluation, compound 3j may be considered lead-like (i.e. a molecular entity suitable for optimization) and, thus, of value in the design of novel, potent and selective adenosine A1 and A2A receptor antagonists.
Concise Total Synthesis of Trichodermamides A, B, and C Enabled by an Efficient Construction of the 1,2-Oxazadecaline Core
Mfuh, Adelphe M.,Zhang, Yu,Stephens, David E.,Vo, Anh X. T.,Arman, Hadi D.,Larionov, Oleg V.
supporting information, p. 8050 - 8053 (2015/07/15)
We report herein a facile and efficient method of the construction of the cis-1,2-oxazadecaline system, distinctive of (pre)trichodermamides, aspergillazine A, gliovirin, and FA-2097. The formation of the 1,2-oxazadecaline core was accomplished by a 1,2-addition of an αC-lithiated O-silyl ethyl pyruvate oxime to benzoquinone, which is followed by an oxa-Michael ring-closure. The method was successfully applied to the concise total synthesis of trichodermamide A (in gram quantities) and trichodermamide B, as well as the first synthesis of trichodermamide C.
Design and synthesis of 3,3′-biscoumarin-based c-Met inhibitors
Xu, Jimin,Ai, Jing,Liu, Sheng,Peng, Xia,Yu, Linqian,Geng, Meiyu,Nan, Fajun
, p. 3721 - 3734 (2014/06/09)
A library of biscoumarin-based c-Met inhibitors was synthesized, based on optimization of 3,3′-biscoumarin hit 3, which was identified as a non-ATP competitive inhibitor of c-Met from a diverse library of coumarin derivatives. Among these compounds, 38 and 40 not only showed potent enzyme activities with IC50 values of 107 nM and 30 nM, respectively, but also inhibited c-Met phosphorylation in BaF3/TPR-Met and EBC-1 cells. This journal is the Partner Organisations 2014.
Synthesis of structurally diverse benzosuberene analogues and their biological evaluation as anti-cancer agents
Tanpure, Rajendra P.,George, Clinton S.,Strecker, Tracy E.,Devkota, Laxman,Tidmore, Justin K.,Lin, Chen-Ming,Herdman, Christine A.,Macdonough, Matthew T.,Sriram, Madhavi,Chaplin, David J.,Trawick, Mary Lynn,Pinney, Kevin G.
supporting information, p. 8019 - 8032 (2014/01/06)
Diversely functionalized, fused aryl-alkyl ring systems hold a prominent position as well-established molecular frameworks for a variety of anti-cancer agents. The benzosuberene (6,7 fused, also referred to as dihydro-5H-benzo[7] annulene and benzocycloheptene) ring system has emerged as a valuable molecular core component for the development of inhibitors of tubulin assembly, which function as antiproliferative anti-cancer agents and, in certain cases, as vascular disrupting agents (VDAs). Both a phenolic-based analogue (known as KGP18, compound 39) and its corresponding amine-based congener (referred to as KGP156, compound 45), which demonstrate strong inhibition of tubulin assembly (low micromolar range) and potent cytotoxicity (picomolar range for KGP18 and nanomolar range for KGP156) are noteworthy examples of such benzosuberene-based compounds. In order to extend the structure-activity relationship (SAR) knowledge base related to benzosuberene anti-cancer agents, a series of eleven analogues (including KGP18) were prepared in which the methoxylation pattern on the pendant aryl ring as well as functional group incorporation on the fused aryl ring were varied. The synthetic approach to these compounds featured a sequential Wittig olefination, reduction, Eaton's reagent-mediated cyclization strategy to achieve the core benzosuberone intermediate, and represented a higher-yielding synthesis of KGP18 (which we prepared previously through a ring-expansion strategy). Incorporation of a fluorine or chlorine atom at the 1-position of the fused aryl ring or replacement of one of the methoxy groups with hydrogen (on the pendant aryl ring of KGP18) led to benzosuberene analogues that were both strongly inhibitory against tubulin assembly (IC50 approximately 1.0 μM) and strongly cytotoxic against selected human cancer cell lines (for example, GI50 = 5.47 nM against NCI-H460 cells with fluoro-benzosuberene analogue 37). A water-soluble phosphate prodrug salt of KGP18 (referred to as KGP265, compound 44) and a water-soluble serinamide salt (compound 48) of KGP156 were also synthesized and evaluated in this study.
Efficient Method for Preparing Functionalized Benzosuberenes
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Page/Page column 12, (2012/06/01)
The disclosed process can efficiently synthesize functionalized benzosuberenes. The process provides an improved method of production of benzosuberene and compounds containing a benzosuberene moiety, which is characterized by a ring closing methodology comprising reaction of a 5-phenylpentanoic acid with Eaton's reagent to form the benzosuberone. The process, optionally, further includes steps for adding a functional group at the ketone position.
A facile demethylation of ortho substituted aryl methyl ethers promoted by AlCl3
Du, Zhen-Ting,Lu, Jing,Yu, Hong-Rui,Xu, Yan,Li, An-Pai
experimental part, p. 222 - 227 (2010/08/04)
An efficient and practical demethylation of ortho substituted aryl methyl ethers using AlCl3 has been developed. This method gives a high conversion, is simple to operate and is cost-effective. A mechanism involving the complexation of AlCl3 with the OMe and the adjacent electron withdrawing group is proposed. Many functional groups can be tolerated in the demethylation process, and 29 examples gave a demethylated product in a yield of 90-98%.
