- Synthetic studies towards the penicisulfuranols: Synthesis of an advanced spirocyclic diketopiperazine intermediate
-
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.
- Gayler, Kevin M.,Lambert, Kyle M.,Wood, John L.
-
-
Read Online
- Unintended Formation of a 26-Membered Cycle in the Course of a Novel Approach to Myricanol, a Strained [7,0]-Metacyclophane
-
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.
- Chiummiento, Lucia,Choppin, Sabine,Colobert, Fran?oise,Hanquet, Gilles,Massé, Paul
-
-
Read Online
- Synthetic studies on naturally occurring coumarins. I. A convenient synthesis of 5,8-dimethoxy- and 7,8-dimethoxycoumarins
-
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.
- Ishii,Kenmotsu,Dopke,Harayama
-
-
Read Online
- Discovery, optimization, and target identification of novel coumarin derivatives as HIV-1 reverse transcriptase-associated ribonuclease H inhibitors
-
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.
- 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)
-
- Synthesis and evaluation of methoxy substituted 2-benzoyl-1-benzofuran derivatives as lead compounds for the development adenosine A1 and/or A2A receptor antagonists
-
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.
- Aucamp, Janine,Janse van Rensburg, Helena D.,Legoabe, Lesetja J.,Terre'Blanche, Gisella
-
-
- Concise Total Synthesis of Trichodermamides A, B, and C Enabled by an Efficient Construction of the 1,2-Oxazadecaline Core
-
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.
- 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)
-
- Design and synthesis of 3,3′-biscoumarin-based c-Met inhibitors
-
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.
- Xu, Jimin,Ai, Jing,Liu, Sheng,Peng, Xia,Yu, Linqian,Geng, Meiyu,Nan, Fajun
-
p. 3721 - 3734
(2014/06/09)
-
- Synthesis of structurally diverse benzosuberene analogues and their biological evaluation as anti-cancer agents
-
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.
- 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)
-
- Efficient Method for Preparing Functionalized Benzosuberenes
-
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.
- -
-
Page/Page column 12
(2012/06/01)
-
- A facile demethylation of ortho substituted aryl methyl ethers promoted by AlCl3
-
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%.
- Du, Zhen-Ting,Lu, Jing,Yu, Hong-Rui,Xu, Yan,Li, An-Pai
-
experimental part
p. 222 - 227
(2010/08/04)
-
- ortho-Formylation of oxygenated phenols
-
Oxygenated phenols are mono-formylated using a mixture of paraformaldehyde, MgCl2, and Et3N in THF. In all cases but one, only one regioisomer of the salicylaldehyde is obtained in good to high yield.
- Akselsen, ?yvind W.,Skatteb?l, Lars,Hansen, Trond Vidar
-
experimental part
p. 6339 - 6341
(2010/02/27)
-
- Total synthesis of streptonigrone
-
(Chemical Equation Presented) A total synthesis of streptonigrone, 1, is described, which incorporates a one-step synthesis of substituted pyridones devised in our laboratory. Other aspects of the synthesis that differentiate the present approach from previous ones are the use of a Conrad-Limpach reaction, rather than the customary Friedlaender methodology, to assemble the quinoline segment of 1, and the implementation of an anionic sequence for the functionalization of a key pyridone intermediate.
- Chan, Bryan K.,Ciufolini, Marco A.
-
p. 8489 - 8495
(2008/02/13)
-
- Total synthesis of natural and unnatural lamellarins with saturated and unsaturated D-rings
-
(Chemical Equation Presented) Twenty-eight natural and unnatural lamellarins with either a saturated or an unsaturated D-ring were synthesized according to our developed synthetic route. The key step involved the Michael addition/ring closure (Mi-RC) of the benzyldihydroisoquinoline and α-nitrocinnamate derivatives, which provided the 2-carboethoxypyrrole intermediates in moderate to good yields (up to 78% yield). Subsequent hydrogenolysis/lactonization furnished lamellarins with a saturated D-ring in excellent yields (up to 93% yield). DDQ oxidation of the saturated lamellarin acetates led directly to the corresponding unsaturated analogues in 54-95% yield. In addition, only two steps in our developed strategy require column chromatography.
- Ploypradith, Poonsakdi,Petchmanee, Thaninee,Sahakitpichan, Poolsak,Litvinas, Nichole D.,Ruchirawat, Somsak
-
p. 9440 - 9448
(2007/10/03)
-
- Synthesis and cytotoxic activities of a new benzo[c]phenanthridine alkaloid, 7-hydroxynitidine, and some 9-oxygenated benzo[c]phenanthridine derivatives.
-
[formula: see text] A new benzo[c]phenanthridine alkaloid, 7-hydroxynitidine, was synthesized by a novel synthetic procedure. The cytotoxic activity of this compound against HeLa S3 cells was strong, but not greater than those of its mother compounds, nitidine and NK109. We also synthesized other 9-oxygenated benzo[c]phenanthridine alkaloids, 7-methoxynitidine, 9-demethylnitidine, nitidine, and fagaronine, and tested their cytotoxic activities. These results suggest that the 7-hydroxy group enhances antitumor activity and an 8- or 9-hydroxy group weakens this activity.
- Nakanishi,Suzuki
-
p. 985 - 988
(2008/02/09)
-
- Hemi-thioacetal pummerer reaction for the synthesis of gliovirin benzylic sulfide models
-
The cyclic hemithioacetal sulfoxide 15 readily undergoes the Pummerer reaction in the presence of carbon nucleophiles to give substitute benzylic sulfides in excellent yields.
- Magnus, Philip,Mitchell, Ian S.
-
p. 9131 - 9134
(2007/10/03)
-
- Isolation, Structure, and Synthesis of Combretastatin C-1
-
A new cell growth inhibitory (PS ED50 2.2 μg/mL) phenanthraquinone designated combretastatin C-1 (2) has been isolated from the African tree Combretum caffrum.The structure (2) assigned combretastatin C-1 was based on high-resolution mass and NMR spectral analyses and confirmed by total syntheses.Synthetic routes 5b -> 6b -> 2 and especially 5c -> 6c -> 2 proved to be quite practical.
- Singh, Sheo Bux,Pettit, George R.
-
p. 4105 - 4114
(2007/10/02)
-
- Syntheses of the Benzylisoquinoline Alkaloids Isosevanine and Berbithine
-
The benzylisoquinoline alkaloids isosevanine (1) and berbithine (2) have been synthesized by alkylation of the Reissert compound (5), derived from 6,7-methylenedioxyisoquinoline, with the appropriate benzyl chlorides (6) and (7) respectively followed by hydrogenolysis of the protecting group.
- Chantimakorn, Vilai,Nimgirawath, Surachai
-
p. 209 - 213
(2007/10/02)
-
- Boron Trichloride as a Selective Demethylating Agent for Hindered Ethers: a Synthesis of the Phytoalexins α- and β-Pyrufuran, a Synthesis of Tri-O-methylleprolomin and its Demethylation
-
Boron trichloride has been found to be an efficient reagent for the selective cleavage of sterically hindered methoxy groups in methoxyarenes.The scope and utility of this reaction are explored with examples drawn from derivatives of benzene, naphtalene, 9,10-dihydrophenanthrene and dibenzofuran.The method is applied to the synthesis of the phytoalexins α- (56) and β-pyrofuran (58) (1,3,4-trimethoxydibenzofuran-2-ol and 1,2,4-trimethoxydibenzofuran-3-ol).A synthesis of tri-O-methylleprolomin (61), a derivative of the unusual lichen metabolite leprolomin (60), is described and its demethylation with boron trichloride is studied.
- Carvalho, Christopher F.,Russo, Albert V.,Sargent, Melvyn V.
-
p. 777 - 792
(2007/10/02)
-
- Aromatic Hydroxylation. Hydroxybenzaldehydes from Bromobenzaldehydes via Reaction of in Situ Generated, Lithiated α-Morpholinobenzyl Alkoxides with Nitrobenzene
-
A general method for the one-step conversion of bromobenzaldehydes to the corresponding hydroxybenzaldehydes has been developed.The method involves in situ protection of the aldehyde function of the bromobenzaldehyde as its lithium morpholinoalkoxide, followed by lithium-bromine exchange, reaction with nitrobenzene at -75 deg C, and a subsequent acidic workup.The method has been applied to the synthesis of 4,5-dimethoxy-3-hydroxy- (1a), 3,5-dimethoxy-2-hydroxy- (2a), 3,5-bis(benzyloxy)-2-hydroxy- (2b), 3,4-dimethoxy-2-hydroxy- (14), 3-hydroxy-4,5-(methylenedioxy)- (16), and 4,5-dimethoxy-2-hydroxybenzaldehydes (18) from the bromobenzaldehydes 4, 12a, 12b, 13, 15, and 17, respectively.
- Sinhababu, Achintya K.,Borchardt, Ronald T.
-
p. 1941 - 1944
(2007/10/02)
-
- SYNTHESIS OF NATURAL ISOFLAVANQUINONES BY THE OXIDATIVE REARRANGEMENT OF CHALCONES WITH THALLIUM(III) NITRATE: ABRUQUINONES A AND B
-
The natural isoflavanquinones abruquinone A and B have been synthesized through the oxidative rearrangement of chalcones with Tl(NO3)3.The previously proposed structures are confirmed.
- Lupi, Alessandro,Marta, Maurizio,Lintas, Graziella,Marini Bettolo, Giovanni Battista
-
p. 625 - 628
(2007/10/02)
-