- Efficient synthesis of dibenzazepine lactams via a sequential Pd-catalyzed amination and aldol condensation reaction
-
A simple and efficient reaction was developed for the synthesis of dibenzazepine lactam derivatives. The core 7-membered azepine ring was formed by a stepwise sequence involving a palladium-catalyzed amination and an aldol condensation.
- Song, Ha-Jeong,Yoon, Eunyoung,Heo, Jung-Nyoung
-
-
Read Online
- Structure-Activity Relationship Study Enables the Discovery of a Novel Berberine Analogue as the RXRα Activator to Inhibit Colon Cancer
-
We reported recently that berberine (Ber), a traditional oriental medicine to treat gastroenteritis, binds and activates retinoid X receptor α (RXRα) for suppressing the growth of colon cancer cells. Here, we extended our studies based on the binding mode of Ber with RXRα by design, synthesis, and biological evaluation of a focused library of 15 novel Ber analogues. Among them, 3,9-dimethoxy-5,6-dihydroisoquinolino[3,2-a]isoquinolin-7-ium chloride (B-12) was identified as the optimal RXRα activator. More efficiently than Ber, B-12 bound and altered the conformation of RXRα/LBD, thereby suppressing the Wnt/β-catenin pathway and colon cancer cell growth via RXRα mediation. In addition, B-12 not only preserved Ber's tumor selectivity but also greatly improved its bioavailability. Remarkably, in mice, B-12 did not show obvious side effects including hypertriglyceridemia as other RXRα agonists or induce hepatorenal toxicity. Together, our study describes an approach for the rational design of Ber-derived RXRα activators as novel effective antineoplastic agents for colon cancer.
- Xu, Beibei,Jiang, Xunjin,Xiong, Jing,Lan, Jun,Tian, Yuan,Zhong, Linhai,Wang, Xinquan,Xu, Ning,Cao, Hanwei,Zhang, Wenqing,Zhang, Hao,Hong, Xiaoting,Zhan, Yan-Yan,Zhang, Yandong,Hu, Tianhui
-
-
Read Online
- Synthesis and crystal structure of (4s)-4-benzyl-3-(4,5-dimethoxy-2-methylbenzoyl)- 2,2-dimethyl-1,3-oxazolidine
-
The synthesis of (4S)-4-benzyl-3-(4,5-dimethoxy-2-methylbenzoyl)- 2,2-dimethyl-1,3-oxazolidine 6 was performed in 7 steps starting from veratraldehyde 7. A new oxidizing system TBHP-ebselen 12 was used for oxidation of 4,5-dimethoxy-2-methylbenzaldehyde 11 into carboxylic acid 13, being the crucial step of the synthesis. The latter was transformed first to chiral amide 14 using (S)-phenylalaninol and then cyclised to oxazolidine 6. The spatial structure and the absolute configuration of the latter one was confirmed by X-ray study.
- Chrzanowskak, Maria,Meissner, Zofia,Chrzanowska, Joanna M.,Gzella, Andrzej K.
-
-
Read Online
- The efficient synthesis and biological evaluation of justicidin B
-
A facile new synthetic method for the preparation of a Type-A 1-arylnaphthalene lactone skeleton was developed and used to synthesise justicidin B and several derivatives. Key synthesis steps included Hauser–Kraus annulation of a phthalide intermediate and Suzuki–Miyaura cross coupling between a triflated naphthalene lactone intermediate and various potassium organotrifluoroborates. With two exceptions, the derivatives showed significant inhibitory effect on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse macrophages. Moreover, several compounds, including justicidin B, had marked cytotoxicity towards six human tumour cell lines.
- Choi, Pilju,Ham, Jungyeob,Jeong, Kyu-Hyuk,Ju, Ha-Neul,Kim, Ji-Yool,Kim, Taejung,Kim, Young-Joo,Kwon, Hyukjoon,Park, Young-Tae,Yoon, Cheol Hee
-
-
Read Online
- Stable Axially Chiral Isomers of Arylnaphthalene Lignan Glycosides with Antiviral Potential Discovered from Justicia procumbens
-
Arylnaphthalene lignans (ANLs) were known to have axial chirality due to the biphenyl skeleton with hindered rotation at the single bond. However, the stable ANL atropisomers have not been isolated from nature until the present study. Phytochemical separation of the methanol extract of the stems and barks of Justicia procumbens led to the isolation of 11 ANL glycosides including four pairs of new atropisomers with stable confirmations at room temperature. Their structures were deduced from elucidation of the extensive spectral data, and their absolute configurations were determined by the circular dichroism, electronic circular dichroism, and X-ray methods as well as the total synthesis of one pair of the atropisomers. The ANL compounds were evaluated for their antiviral potential, and it was found that they displayed great antiviral activity discrepancy between a pair of atropisomers due to the geometric orientation. The 1′P-oriented atropisomers showed much more significant antiviral potency than their corresponding 1′M-oriented counterparts. The biological activity discrepancy caused by the axial chirality will not only inspire synthetic design of novel ANL atropisomers to enrich the structural diversity, but also provide important hints to direct the synthetic approaches toward the antiviral drug development of ANL compounds.
- Zhao, Yang,Ku, Chuen-Fai,Xu, Xin-Ya,Tsang, Nga-Yi,Zhu, Yu,Zhao, Chen-Liang,Liu, Kang-Lun,Li, Chuang-Chuang,Rong, Lijun,Zhang, Hong-Jie
-
p. 5568 - 5583
(2021/05/07)
-
- Patentiflorin A Analogs as Antiviral Agents
-
The present disclosure relates to patentiflorin A analogs that are useful as antivirals, such as anti-HIV, anti-coronaviral, anti-Ebola viral, and anti-influenza viral agents and methods of use thereof.
- -
-
Paragraph 0108; 0275-0276
(2021/03/05)
-
- Diphyllin and application thereof in preparation of medicine for preventing or treating diabetes mellitus
-
The invention belongs to the technical field of medicine, and particularly relates to diphyllin represented by a formula I and an application of the diphyllin in preparation of medicine for preventingor treating diabetes mellitus, and experiments prove that the compound can improve insulin sensitivity of mice and reduce blood sugar. The compound is expected to be developed into a medicine for preventing or treating diabetes.
- -
-
Paragraph 0029; 0030; 0032
(2020/06/05)
-
- Diphyllin Improves High-Fat Diet-Induced Obesity in Mice Through Brown and Beige Adipocytes
-
Brown adipose tissue (BAT) and beige adipose tissue dissipate metabolic energy and mediate nonshivering thermogenesis, thereby boosting energy expenditure. Increasing the browning of BAT and beige adipose tissue is expected to be a promising strategy for combatting obesity. Through phenotype screening of C3H10-T1/2 mesenchymal stem cells, diphyllin was identified as a promising molecule in promoting brown adipocyte differentiation. In vitro studies revealed that diphyllin promoted C3H10-T1/2 cell and primary brown/beige preadipocyte differentiation and thermogenesis, which resulted increased energy consumption. We synthesized the compound and evaluated its effect on metabolism in vivo. Chronic experiments revealed that mice fed a high-fat diet (HFD) with 100 mg/kg diphyllin had ameliorated oral glucose tolerance and insulin sensitivity and decreased body weight and fat content ratio. Adaptive thermogenesis in HFD-fed mice under cold stimulation and whole-body energy expenditure were augmented after chronic diphyllin treatment. Diphyllin may be involved in regulating the development of brown and beige adipocytes by inhibiting V-ATPase and reducing intracellular autophagy. This study provides new clues for the discovery of anti-obesity molecules from natural products.
- Duan, Ya-Nan,Ge, Xiang,Jiang, Hao-Wen,Zhang, Hong-Jie,Zhao, Yu,Li, Jin-Long,Zhang, Wei,Li, Jing-Ya
-
-
- Enantioselective Synthesis of Isoxazolines Enabled by Palladium-Catalyzed Carboetherification of Alkenyl Oximes
-
Reported here is a highly efficient Pd/Xiang-Phos catalyzed enantioselective carboetherification of alkenyl oximes with either aryl or alkenyl halides, delivering various chiral 3,5-disubstituted and 3,5,5-trisubstituted isoxazolines in good yields with u
- Chen, Mingjie,Li, Wenbo,Wang, Lei,Wang, Yuzhuo,Zhang, Junliang,Zhang, Kenan
-
supporting information
p. 4421 - 4427
(2020/02/11)
-
- COMPOUNDS FOR THE INHIBITION OF UNREGULATED CELL GROWTH
-
The present invention discloses compounds for inhibition of uncontrolled cell proliferation particularly cancer stem cells. Particularly, the invention relates to compounds of Formula I to XXII for the treatment of cancer.
- -
-
Page/Page column 34-35
(2020/07/14)
-
- Synthesis of Cyclopropanoids via Substrate-Based Cyclization Pathways
-
A series of unexpected reactions triggered by the dimethyloxosulfonium methylide led to the discovery of unconventional approaches for the synthesis of cyclopropa-fused tetralones and indeno-spirocyclopropanes. These highly functionalized structures were further elaborated in one step to privileged scaffolds such as tetralones, indenones, and fluorenones. As a whole, the results presented herein establish new diversity-oriented folding pathways.
- Mishra, Uttam K.,Patel, Kaushalendra,Ramasastry
-
supporting information
p. 175 - 179
(2019/01/04)
-
- Catalytic Dibenzocyclooctene Synthesis via Cobalt(III)–Carbene Radical and ortho-Quinodimethane Intermediates
-
The metalloradical activation of ortho-benzallylaryl N-tosyl hydrazones with [Co(TPP)] (TPP=tetraphenylporphyrin) as the catalyst enabled the controlled exploitation of the single-electron reactivity of the redox non-innocent carbene intermediate. This method offers a novel route to prepare eight-membered rings, using base metal catalysis to construct a series of unique dibenzocyclooctenes through selective Ccarbene?Caryl cyclization. The desired eight-membered-ring products were obtained in good to excellent yields. A large variety of aromatic substituents are tolerated. The proposed reaction mechanism involves intramolecular hydrogen atom transfer (HAT) to CoIII–carbene radical intermediates followed by dissociation of an ortho-quinodimethane that undergoes 8π cyclization. The mechanism is supported by DFT calculations, and the presence of radical-type intermediates was confirmed by trapping experiments.
- te Grotenhuis, Colet,van den Heuvel, Naudin,van der Vlugt, Jarl Ivar,de Bruin, Bas
-
supporting information
p. 140 - 145
(2017/12/13)
-
- ANTICANCER COMPOUNDS
-
The present invention discloses compounds for inhibition of uncontrolled cell proliferation particularly in cancer stem cells. Particularly, the invention relates to compounds of Formula III to XIV for the treatment of cancer, such as breast and prostate cancer.
- -
-
Page/Page column 47; 48; 49
(2018/11/22)
-
- Synthesis and antiproliferative activity of derivatives of the phyllanthusmin class of arylnaphthalene lignan lactones
-
A series of arylnaphthalene lignan lactones based on the structure of the phyllanthusmins, a class of potent natural products possessing diphyllin as the aglycone, has been synthesized and screened for activity against multiple cancer cell lines. SAR exploration was performed on both the carbohydrate and lactone moieties of this structural class. These studies have revealed the importance of functionalization of the carbohydrate hydroxy groups with both acetylated and methylated analogues showing increased potency relative to those with unsubstituted sugar moieties. In addition, the requirement for the presence and position of the C-ring lactone has been demonstrated through reduction and selective re-oxidation of the lactone ring. The most potent compound in this study displayed an IC50 value of 18 nM in an HT-29 assay with several others ranging from 50 to 200 nM. In an effort to elucidate their potential mechanism(s) of action, the DNA topoisomerase IIa inhibitory activity of the most potent compounds was examined based on previous reports of structurally similar compounds, but does not appear to contribute significantly to their antiproliferative effects.
- Woodard, John L.,Huntsman, Andrew C.,Patel, Pratiq A.,Chai, Hee-Byung,Kanagasabai, Ragu,Karmahapatra, Soumendrakrishna,Young, Alexandria N.,Ren, Yulin,Cole, Malcolm S.,Herrera, Denisse,Yalowich, Jack C.,Kinghorn, A. Douglas,Burdette, Joanna E.,Fuchs, James R.
-
p. 2354 - 2364
(2018/04/16)
-
- An Optimized and General Synthetic Strategy To Prepare Arylnaphthalene Lactone Natural Products from Cyanophthalides
-
A simple method for the preparation of arylnaphthalene lactone natural products was developed and used to synthesize diphyllin (10), justicidin A (12), cilinaphthalide B (13), taiwanin E (15), chinensinaphthol (16), taiwanin E methyl ether (17), chinensin
- Kim, Taejung,Jeong, Kyu Hyuk,Kang, Ki Sung,Nakata, Masaya,Ham, Jungyeob
-
p. 1704 - 1712
(2017/04/13)
-
- JUSTICIDIN B DERIVATIVES OF ARYLNAPHTHALENE LIGNAN STRUCTURE AND METHOD FOR PRODUCING THE SAME
-
The present invention relates to a novel manufacturing method of an aryl naphthalene lignan compound. For the aryl naphthalene lignan-type compound and derivative synthesis of the present invention, a naphthalene skeleton center is built at first and an a
- -
-
Paragraph 0126-0128
(2016/11/28)
-
- Synthesis of Diverse 6-Oxa-allocolchicinoids by a Suzuki-Miyaura Coupling, Acid-Catalyzed Intramolecular Transacetalization Strategy
-
The synthesis of allocolchicine analogues is of importance as these compounds have been found to possess promising anticancer activity by affecting tubulin polymerization. In this paper, the synthesis of 28 novel substituted 6-oxa-allocolchicinoids is rep
- Yadav, Dharmendra B.,Taleli, Lebusetsa,Van Der Westhuyzen, Alet E.,Fernandes, Manuel A.,Dragoun, Maxim,Prokop, Aram,Schmalz, Hans-Günther,De Koning, Charles B.,Van Otterlo, Willem A. L.
-
p. 5167 - 5182
(2015/08/18)
-
- Water-soluble isoindolo[2,1-a]quinoxalin-6-imines: In vitro antiproliferative activity and molecular mechanism(s) of action
-
Water-soluble isoindoloquinoxalin (IIQ) imines and the corresponding acetates were conveniently prepared from the key intermediates 2-(2′-aminophenyl)-2H-isoindole-1-carbonitriles obtained by a Strecker reaction between substituted 1,2-dicarbaldehydes and 1,2-phenylenediamines. Both series were screened by the National Cancer Institute (Bethesda, MD) and showed potent antiproliferative activity against a panel of 60 human tumor cell lines. Several of the novel compounds showed GI50 values at a nanomolar level on the majority of the tested cell lines. Among IIQ derivatives, methoxy substituents at positions 3 and 8 or/and 9 were especially effective in impairing cell cycle progression and inducing apoptosis in cancer cells. These effects were associated to IIQ-mediated impairment of tubulin polymerization at pharmacologically significant concentrations of tested compounds. In addition, impaired DNA topoisomerase I functions and perturbation in telomere architecture were observed in cells exposed to micromolar concentrations of IIQ derivatives. The above results suggest that IIQ derivatives exhibit multi-target cytotoxic activities.
- Parrino, Barbara,Carbone, Anna,Ciancimino, Cristina,Spanò, Virginia,Montalbano, Alessandra,Barraja, Paola,Cirrincione, Girolamo,Diana, Patrizia,Sissi, Claudia,Palumbo, Manlio,Pinato, Odra,Pennati, Marzia,Beretta, Giovanni,Folini, Marco,Matyus, Peter,Balogh, Balázs,Zaffaroni, Nadia
-
p. 149 - 162
(2015/03/18)
-
- PENTAARYLBIIMIDAZOLE COMPOUND AND METHOD FOR PRODUCING THE COMPOUND
-
PROBLEM TO BE SOLVED: To provide an industrially usable photochromic compound which solves problems of a conventional photochromic material that the material is insufficient in terms of coloring and decoloring speeds and durability, and that there are man
- -
-
Paragraph 0057
(2018/10/10)
-
- ARYLNAPHTHALENE LACTONE DERIVATIVES AND METHODS OF MAKING AND USING THEREOF
-
A series of natural products including phyllanthusum, an arylnaphthalene lignan derivative, with anticancer and antitumor and immurtostimulating activity are disclosed. The invention further encompasses methods of adding water solubilizing groups to the arylrings that include phosphonyl groups.
- -
-
-
- METHOD FOR PREPARATION OF JUSTICIDIN A DERIVATIVES OF ARYLNAPHTHALENE LIGNAN STRUCTURE
-
The present disclosure relates to a novel method for preparing an arylnaphthalene lignan compound. In synthesis of arylnaphthalene lignan compounds and derivatives according to the present disclosure, a naphthalene backbone may be constructed first and an
- -
-
Paragraph 38; 55; 159; 160; 161; 162
(2014/08/19)
-
- Synthesis and cytotoxicity evaluation of a novel justicidin G analogue and its phosphate ester
-
The novel justicidin G analogue 13 and its phosphate ester 15 were synthesized as potential anticancer agents in several steps starting from commercially available methyl gallate and veratraldehyde. The cytotoxicity of the intermediates was tested against HCT-8, BEL-7402, KETR3, HELA, BGC-823, KB and MCF-7 cell lines by the MTT test, and compound 15 exhibited significant cytotoxicity in HELA and KB cell lines.
- Wang, Sheng-Peng,Tong, Yuan-Feng,Wang, Dong-Mei,Wang, Nan,Yan, Zheng,Huang, Ping,Wu, Song
-
p. 1044 - 1046
(2014/08/18)
-
- Pentaarylbiimidazole, PABI: An easily synthesized fast photochromic molecule with superior durability
-
We report a new type of fast photochromic imidazole dimer, pentaarylbiimidazole (PABI), which shows a few μs fast photochromism with high fatigue resistance against light irradiation. PABI has an unusual spiroconjugated imidazoisoindole skeleton and its d
- Yamashita, Hiroaki,Abe, Jiro
-
supporting information
p. 8468 - 8471
(2014/07/22)
-
- Organocatalytic, Enantioselective, intramolecular oxa-michael reaction of alkoxyboronate: A new strategy for enantioenriched 1-substituted 1,3-Dihydroisobenzofurans
-
An unprecedented strategy for the synthesis of enantioenriched 1-substituted 1,3-dihydroisobenzofurans via an enantioselective oxa-Michael reaction of o-alkoxyboronate containing chalcone (II) has been accomplished employing cinchona alkaloid based squara
- Ravindra, Barnala,Das, Braja Gopal,Ghorai, Prasanta
-
supporting information
p. 5580 - 5583
(2015/02/19)
-
- Synthesis and bioevaluation of novel arylnaphthalene lignans as anticancer agents
-
Novel arylnaphthalene lignans were synthesized and their structures were established by 1H NMR, 13C NMR, and HRMS. These compounds were evaluated for their in vitro cytotoxicity against cancer cell lines by MTT assay. Compound 5d possessed the highest cytotoxicity against KB cells. Apoptosis of KB cells treated with 5d was observed by acridine orange and ethidium bromide double staining assay. Western blot analysis disclosed that 5d induced apoptosis via mitochondrial pathway accompanied by an increased expression of Bax and a decreased expression of Bcl-2.
- Zhao, Yu,Hui, Jie,Zhu, Li
-
p. 2505 - 2510
(2013/07/26)
-
- One-pot syntheses of isoquinolin-3-ones and benzo-1,4-diazepin-2,5-diones utilizing Ugi-4CR post-transformation strategy
-
One-pot and efficient syntheses of structurally diverse isoquinolin-3-ones and isoquinolin-3-one-based benzo-1,4-diazepin-2,5-diones have been developed. The notable features of the process include the Ugi condensation of monomasked phthalaldehydes with a
- Che, Chao,Li, Song,Yu, Zhixiong,Li, Fangfang,Xin, Shengchang,Zhou, Liyan,Lin, Shuo,Yang, Zhen
-
supporting information
p. 202 - 207
(2013/05/09)
-
- Total synthesis of 60-hydroxyjusticidin A
-
The first total synthesis of 6′-hydroxyjusticidin A, isolated from Justicia procumbens L. with good inhibitory activity against cancer cells, has been accomplished. The structure was confirmed by 1H NMR, 13C NMR, and HR-ESI-MS. The key steps involved a Diels-Alder cycloaddition reaction and a reduction in NaBH4.
- Xiong, Lu,Bi, Ming-Gang,Wu, Song,Tong, Yuan-Feng
-
scheme or table
p. 322 - 326
(2012/08/28)
-
- PROCESS FOR THE SYNTHESIS OF CLEISTANTHIN
-
The present invention relates to a process for preparing compound of formula (I) that is Cleistanthin A. The process comprises the steps of reacting compound of formula (II) with compound of formula (III) in the presence of a first solvent, quarternary ammonium salt and first alkali to form compound of formula (IV). The compound of formula (IV) is further treated with a second solvent and a second alkali to form compound of formula (I). The present invention also relates to the preparation of salt of compound of formula (IV) that is Cleistanthin A acetate.
- -
-
Page/Page column 6
(2012/02/06)
-
- Dihydro[c]benzazepin-3-ones via conjugated nitrone-allene precursors
-
Treatment of o-propargylaryl nitrones with base provided 1,2-dihydro[c]benzazepin-3-ones in good yields. The straightforward transformation is explained on the basis of a multistep rearrangement involving conjugated allene-nitrones as precursors of a 1,7-dipolar electrocyclization process that is followed by further bond reorganizations.
- Knobloch, Karin,Eberbach, Wolfgang
-
p. 1117 - 1120
(2007/10/03)
-
- Oxidative Intramolecular Phenolic Coupling Reaction Induced by a Hypervalent Iodine(III) Reagent: Leading to Galanthamine-Type Amaryllidaceae Alkaloids
-
By extending our oxidative phenol-coupling reactions using a hypervalent iodine(III) reagent, a versatile synthetic procedure for the galanthamine-type Amaryllidaceae alkaloids was accomplished. The first total synthesis of (±)-sanguinine and the total syntheses of (±)-galanthamine, (±)- narwedine, (±)-lycoramine, and (±)-norgalanthamine were also successfully carried out.
- Kita, Yasuyuki,Arisawa, Mitsuhiro,Gyoten, Michiyo,Nakajima, Makiko,Hamada, Ryuji,Tohma, Hirofumi,Takada, Takeshi
-
p. 6625 - 6633
(2007/10/03)
-
- 1,3-benzodioxole and 1,2-dialkoxybenzene derivatives as ocular hypotensive agents
-
Compounds of the formula STR1 where the symbols have the meaning defined in the specification, are capable of lowering intraocular pressure in the eye of a mammal.
- -
-
-
- Hindered rotation in arylnaphthalene lignans
-
Many arylnaphthalene lignans show biological activity and although few of them contain stereogenic centers, they may nevertheless be chiral if there is hindered rotation about the aryl-naphthalene bond. A relatively high barrier to rotation may give rise to separable rotational enantiomers (atropisomers) which might have quite different pharmacological properties. In order to investigate this possibility we have synthesized the natural products justicidin A, justicidin B, retro-helioxanthin, retro-justicidin B, and helioxanthin as well as four other arylnaphthalenes lignan analogs. We have studied the aryl-naphthalene rotational barrier in these compounds by dynamic NMR and HPLC and find barriers to rotation ranging from 16.9 to 21.5 kcal/mol. This translates to half-lives for individual atropisomers of less than 10 min at room temperature. The experimentally found barriers are compared to those obtained from molecular orbital calculations.
- Charlton, James L.,Oleschuk, Curtis J.,Chee, Gaik-Lean
-
p. 3452 - 3457
(2007/10/03)
-
- The asymmetric synthesis of aryltetralin lignans: (-)-isolariciresinol dimethyl ether and (-)-deoxysikkimotoxin
-
The total asymmetric syntheses of (-)-isolariciresinol dimethyl ether (6) and (-)-deoxysikkimotoxin (7) have been carried out, in an attempt to exploit a synthetic strategy recently developed for the synthesis of (-)-deoxypodophyllotoxin (1, R1 = -CH2-, Ar = 3,4,5-trimethoxyphenyl). In so doing, a generalized method for the synthesis of aryltetralin lignans has been developed that should be applicable to a variety of substitution patterns and stereochemistries. A one-pot, 100% regio-selective reduction-lactonization procedure has been developed for the conversion of the ester 18b to (-)-deoxysikkimotoxin, which gave 93% isolated yield in that step.
- Coltart, Don M.,Charlton, James L.
-
-
- 1,3-benzodioxole and 1,2-dialkoxybenzene derivatives as ocular hypotensive agents
-
Compounds of the formula STR1 where W is (CH2)n where n is 1 or 2, or n is 0 and W represents lower alkyl groups attached to each oxygen; m is an integer between 1 and 8; R1 is COOH or a pharmaceutically acceptable salt th
- -
-
-
- 1,3-benzodioxole and 1,2-dialkoxybenzene derivatives as ocular hypotensive agents
-
Compounds of the formula STR1 where W is (CH2)n where n is 1 or 2, or n is O and W represents lower alkyl groups attached to each oxygen; m is an integer between 1 and 8; R1 is COOH or a pharmaceutically acceptable salt th
- -
-
-
- Vinyl Azides in Heterocyclic Synthesis. Part 10. Synthesis of the Isoindolobenzazepine Alkaloid Lennoxamine
-
A total synthesis of the isoindolobenzazepine alkaloid lennoxamine (1), by a route involving vinyl azide chemistry, is described.Model studies on the azidocinnamates (12) and (13) revealed a striking difference between the (E)- and (Z)-isomers; whereas the (Z)-isomer (12) gave largely the 1-benzylisoquinoline (15) on decomposition, the (E)-isomer (13) gave the 2-aryl-3-benzazepine (14) as the major product.Consequently, in the lennoxamine synthesis, the azidocinnamate (26) bearing the (E)-alkenyl side chain, prepared from 6-bromopiperonal via the (E)-stilbene aldehyde (25) (Scheme 4), was decomposed to give the key 2-aryl-3-benzazepin e (27).Reduction of the double bonds in (27) was accompanied by cyclisation to the tetrahydroisoindolobenzazepine (30), which was converted into lennoxamine (1) by reduction of the ester group to an aldehyde, and decarbonylation.
- Moody, Christopher J.,Warrellow, Graham J.
-
p. 2929 - 2936
(2007/10/02)
-
- Asymmetric Lignan Synthesis: Isolariciresinol Dimethyl Ether
-
An asymmetric synthesis of the lignan (+)-isolariciresinol dimethyl ether 1 in nine steps and 13percent yield (83percent optical purity) from veratraldehyde is described.Veratraldehyde was converted to 6-(3,4-dimethoxybenzyl)veratraldehyde 3 by bromination, acetal formation, metalation, and coupling to 3,4-dimethoxybenzyl bromide. 3 was irradiated in the presence of SO2 to give the 3-hydroxy-1-aryl-1,3-dihydrobenzothiophene 2,2-dioxide 4, which was converted to the (R)-1-phenylethoxy derivative 5b. 5b on heating with dimethyl fumarate gave a mixture of primarily two diastereomeric cycloadducts 7b and 7b', both of which had the 1,2-trans, 2,3-trans , 3,4-cis stereochemistry.The major adduct 7b was subsequently assigned the stereochemistry 1S,2R,3S,4S.Separation and hydrogenolysis of the major adduct gave the diester 8, 1S,2R,3R, which was reduced with LiAlH4 to give (+)-isolariciresinol dimethyl ether 1.A racemic synthesis was also carried out via the methoxy sulfone 5a and its trans isomer 5a' in 33percent yield.
- Charlton, James L.,Alauddin, M. M.
-
p. 3490 - 3493
(2007/10/02)
-