- Substituted Tetraethynylethylene–Tetravinylethylene Hybrids
-
A general synthetic approach to molecular structures that are hybrids of tetraethynylethylene (TEE) and tetravinylethylene (TVE) is reported. The synthesis permits the controlled preparation of many previously inaccessible structures, including examples w
- Connor, Kieran P. E.,Horvath, Kelsey L.,Magann, Nicholas L.,Sherburn, Michael S.,Sowden, Madison J.,Westley, Erin
-
supporting information
p. 977 - 986
(2022/02/03)
-
- Synthesis of Optically Active N -(4-Hydroxynon-2-enyl)pyrrolidines: Key Building Blocks in the Total Synthesis of Streptomyces coelicolor Butanolide 5 (SCB-5) and Virginiae Butanolide A (VB-A)
-
Starting from 5-methylhexanal and (S)-configured N -propargylprolinol ethers, coupling delivered N -(4-hydroxynon-2-ynyl)prolinol derivatives as mixtures of C4 diastereomers. Resolution of the epimers succeeded after introduction of an (R)-mandelic ester derivative and subsequent HPLC separation. Alternatively, suitable oxidation gave the corresponding alkynyl ketone. Midland reagent controlled diastereoselective reduction afforded a defined configured propargyl alcohol with high selectivity. LiAlH 4reduction and Mosher analyses of the allyl alcohols enabled structure elucidation. The suitably protected products are used as key intermediates in enantioselective Streptomyces γ-butyrolactone signaling molecule total syntheses.
- Donges, Jonas,Hofmann, Sandra,Walter, Johannes C.,Reichertz, Julia,Brüggemann, Moritz,Frank, Andrea,Nubbemeyer, Udo
-
supporting information
p. 2632 - 2642
(2021/04/27)
-
- Enantioselective Total Synthesis of Cerorubenic Acid-III via Type II [5+2] Cycloaddition Reaction
-
The first enantioselective total synthesis of cerorubenic acid-III is described in detail. Different strategies and attempts, based on a type II [5+2] cycloaddition reaction, leading to the bicyclo[4.4.1] ring system with a strained bridgehead double bond, are depicted. Furthermore, sodium naphthalenide was found to be efficient in the chemoselective reduction of 8-oxabicyclo[3.2.1]octene, with three transformations completed in one operation. An unusual SN1 transannular cyclization reaction was applied to construct the synthetically challenging vinylcyclopropane moiety. This strategy enabled the total synthesis of cerorubenic acid-III in 19 steps.
- Liu, Xin,Liu, Junyang,Wu, Jianlei,Li, Chuang-Chuang
-
p. 11125 - 11139
(2021/05/29)
-
- PROBE FOR DETECTING CARBAPENEM-RESISTANT BACTERIA AND USE THEREOF
-
The present disclosure relates to a compound represented by Chemical Formula 1, a probe for detecting antibiotic-resistant bacteria, which includes the compound, a composition containing the compound, a kit including the compound and a method for detectin
- -
-
Paragraph 0085; 0099; 0100
(2021/09/10)
-
- Synthesis of (Z)-alkene-containing linear conjugated dienyl homoallylic alcohols by a palladium-catalyzed three-component reaction
-
A synthesis of (Z)-alkene-containing linear conjugated dienyl homoallylic alcohols by using a palladium-catalyzed three-component reaction has been developed. This method shows good functional-group compatibility and generality, with high diastereoselectivity. Additionally, in many cases, the present method controls the alkene stereochemistry of the newly formed C-C bond and overcomes the inherent preference for (E)-alkene formation, giving (Z, E)- and (Z, Z)-products.
- Horino, Yoshikazu,Sakamoto, Juri,Murakami, Miki,Sugata, Miki
-
supporting information
p. 1323 - 1327
(2020/08/21)
-
- DERIVATIVES OF THAILANSTATIN A, METHODS OF TREATMENT AND METHODS OF SYNTHESIS THEREOF
-
In one aspect, the present disclosure provides analogs of thailanstatin of the formula wherein the variables are as defined herein. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds disclosed herein.
- -
-
Paragraph 0313
(2020/02/10)
-
- Total Synthesis of Lajollamycin B
-
The first total synthesis of lajollamycin B, a structurally novel nitro-tetraene spiro-β-lactone/γ-lactone antibiotic, is described. The convergent synthesis involves the construction of the C8′–C11′ nitrodienylstannane and its coupling with the segment prepared from the C1′–C7′ ω-iodoheptadienoic acid and the right-hand heterocyclic fragment, which has been utilized for our previous syntheses of oxazolomycin A. The revision of the geometry of the terminal Δ10′, 11′-double bond from E to Z is also described for the structure of natural lajollamycin B.
- Nishimaru, Tatsuya,Eto, Kohei,Komine, Keita,Ishihara, Jun,Hatakeyama, Susumi
-
p. 7927 - 7934
(2019/05/27)
-
- Synthesis of the C1-C12 Fragment of Calyculin C
-
Calyculins are a class of highly cytotoxic metabolites originally isolated from the marine sponge Discodermia calyx. To date, a total of twelve different calyculins (A-J) and calyculinamides (A, B and F) have been described, the most abundant (in D. calyx
- Konstantinova, Olga V.,Koskinen, Ari M.P.
-
p. 285 - 295
(2019/01/04)
-
- Versatile synthetic route to carbocyclic N-Acetylneuraminic acid and its derivatives
-
Sialic acid (N-acetylneuraminic acid) is a carbohydrate that possess a nine carbon backbone, and it is often found at the termini of glycoconjugates in biological systems. Because of this prominence many syntheses have reported routes to sialic acid and m
- Mohan, Sankar,Thompson, John R.,Pinto, B. Mario,Bennet, Andrew J.
-
p. 5213 - 5221
(2018/05/29)
-
- Total Synthesis of the Marine Macrolide Amphidinolide F
-
A new and efficient convergent approach toward the synthesis of amphidinolide F is described through the assembly of three fragments. The two trans-tetrahydrofurans were built by a diastereoselective C-glycosylation with titanium enolate of bulky N-acetyloxazolidinethiones. The side chain was inserted by a Liebeskind-Srogl cross-coupling reaction. A sulfone condensation/desulfonylation sequence, a Stille cross-coupling, and a macrolactonization were applied to connect the fragments.
- Ferrié, Laurent,Fenneteau, Johan,Figadère, Bruno
-
supporting information
p. 3192 - 3196
(2018/06/11)
-
- SYNTHESIS OF DISORAZOLES AND ANALOGS THEREOF AS POTENT ANTICANCER AGENTS
-
In one aspect, the present disclosure provides disorazole analogs of the formula: Formula (I) wherein the variables are as defined herein. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds disclosed herein. Additionally, drug conjugates with cell targeting moieties of the compounds are also provided.
- -
-
Page/Page column 89; 116
(2019/01/11)
-
- Total Syntheses of Disorazoles A1 and B1 and Full Structural Elucidation of Disorazole B1
-
Described herein are the first total syntheses of naturally occurring antitumor agents disorazoles A1 and B1 and the full structural assignment of the latter. The syntheses were achieved through convergent strategies employing enantioselective constructions of the required building blocks, including a novel Sharpless epoxidation/enzymatic kinetic resolution of stannane-containing substrates that led selectively to both enantiomeric forms of an epoxy vinyl stannane, and a series of coupling reactions, including a Wittig reaction, a Suzuki coupling, a Stille coupling, a Yamaguchi esterification and a Yamaguchi macrolactonization.
- Nicolaou,Bellavance, Gabriel,Buchman, Marek,Pulukuri, Kiran Kumar
-
supporting information
p. 15636 - 15639
(2017/11/14)
-
- Total Synthesis of (-)-Marinisporolide C
-
The first total synthesis of (-)-marinisporolide C is described, which establishes unequivocally the relative and absolute configuration of this oxopolyene macrolide. Key features of this synthesis include a series of highly stereoselective aldol reactions followed by directed reductions to build the polyol domain, a Stille cross-coupling reaction to assemble the polyene, and an intramolecular Horner-Wadsworth-Emmons olefination to forge the macrocyclic ring. Despite the initial approach to marinisporolide A using a Yamaguchi macrolactonization reaction that was unsuccessful due to steric hindrance of the oxygen at the C33 position, we were able to prepare a known derivative of marinisporolide A and consequently confirm its stereochemical assignment.
- Dias, Luiz C.,De Lucca, Emilio C.
-
p. 3019 - 3045
(2017/03/23)
-
- Total Synthesis of Thailanstatin A
-
The total synthesis of the spliceosome inhibitor thailanstatin A has been achieved in a longest linear sequence of nine steps from readily available starting materials. A key feature of the developed synthetic strategy is the implementation of a unique, biomimetic asymmetric intramolecular oxa-Michael reaction/hydrogenation sequence that allows diastereodivergent access to highly functionalized tetrahydropyrans, which can be used for the synthesis of designed analogues of this bioactive molecule.
- Nicolaou,Rhoades, Derek,Lamani, Manjunath,Pattanayak, Manas R.,Kumar, S. Mothish
-
supporting information
p. 7532 - 7535
(2016/07/06)
-
- Palladium N-Heterocyclic Carbene Precatalyst Site Isolated in the Core of a Star Polymer
-
An approach for supporting a Pd-NHC complex on a soluble star polymer with nanoscale dimensions is described. The resulting star polymer catalyst exhibits excellent activity in cross-coupling reactions, is stable in air and moisture, and is easily recoverable and recyclable. These properties are distinct and unattainable with the small-molecule version of the same catalyst.
- Bukhryakov, Konstantin V.,Mugemana, Clément,Vu, Khanh B.,Rodionov, Valentin O.
-
supporting information
p. 4826 - 4829
(2015/10/12)
-
- Synthesis of a stereoisomer of wortmannilactone C - failure and success
-
Abstract A diastereomer of wortmannilactone C was synthesized according to a versatile strategy from tert-butyl 3-hydroxypropanoate and ethyl (R)-3-hydroxybutanoate, by using versatile organometallic reagents to control four stereogenic centers out of five. The successful strategy consists of the construction of the C13-C17 triene by using a Liebeskind coupling and the construction of the C2-C7 triene by utilizing a Horner-Wadsworth-Emmons reaction to form the macrocycle.
- Dittoo, Aurélia,Brandt, Damien,Bellosta, Véronique,Cossy, Janine
-
p. 5835 - 5848
(2015/08/03)
-
- Total Synthesis of the Oxopolyene Macrolide (-)-Marinisporolide C
-
The first total synthesis of (-)-marinisporolide C was performed in 25 steps (longest linear sequence) and an overall yield of 1%. Due to the high degree of convergence and robustness, the C9-C35 fragment that corresponds to the polyol portion was obtaine
- Dias, Luiz C.,De Lucca, Emílio C.
-
supporting information
p. 6278 - 6281
(2016/01/09)
-
- Chemoenzymatic synthesis of spinosyn A
-
Following the biosynthesis of polyketide backbones by polyketide synthases (PKSs), post-PKS modifications result in a significantly elevated level of structural complexity that renders the chemical synthesis of these natural products challenging. We report herein a total synthesis of the widely used polyketide insecticide spinosyn A by exploiting the prowess of both chemical and enzymatic methods. As more polyketide biosynthetic pathways are characterized, this chemoenzymatic approach is expected to become readily adaptable to streamlining the synthesis of other complex polyketides with more elaborate post-PKS modifications.
- Kim, Hak Joong,Choi, Sei-Hyun,Jeon, Byung-Sun,Kim, Namho,Pongdee, Rongson,Wu, Qingquan,Liu, Hung-Wen
-
supporting information
p. 13553 - 13557
(2015/01/09)
-
- TRICYCLIC COMPOUNDS AND METHODS OF MAKING AND USING SAME
-
The invention provides tricyclic compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2.
- -
-
Paragraph 00183; 00184
(2014/05/24)
-
- TRICYCLIC COMPOUNDS FOR USE IN THE TREATMENT AND/OR CONTROL OF OBESITY
-
The invention provides tricyclic compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against me
- -
-
Paragraph 00545-00547
(2014/05/24)
-
- METHODS OF TREATING LIVER DISEASES
-
The invention provides tricyclic compounds and their use in treating liver disorders, such as non-alcoholic steatohepatitis and related disorders (e.g., fibrosis). The compounds are contemplated to have activity against methionyl aminopeptidase 2.
- -
-
Paragraph 00252-00253
(2014/05/24)
-
- Modular synthesis of polyene side chain analogues of the potent macrolide antibiotic etnangien by a flexible coupling strategy based on hetero-bis-metallated alkenes
-
An efficient procedure for the concise synthesis of hetero-bis-metallated alkenes as useful building blocks for the modular access to highly elaborate polyenes and stabilized analogues is reported. By applying these bifunctional olefins in convergent Stille/Suzuki-Miyaura couplings, novel, carefully selected side chain analogues of the potent RNA polymerase inhibitor etnangien were synthesized by a modular late stage coupling strategy and evaluated for antibacterial and antiproliferative activities. The Royal Society of Chemistry 2013.
- Altendorfer, Mario,Raja, Aruna,Sasse, Florenz,Irschik, Herbert,Menche, Dirk
-
p. 2116 - 2139
(2013/04/23)
-
- TRICYCLIC HETEROAROMATIC COMPOUNDS AS ALPHA-SYNUCLEIN LIGANDS
-
Derivatives of phenothiazine, phenoxazine, and phenazine compounds and their use as α-synuclein ligands are described. Also described are methods of using these compounds and their radiolabeled analogs for the detection, monitoring, and treatment of synucleinopathies, including Parkinson's disease.
- -
-
Paragraph 0158
(2013/12/04)
-
- TRICYCLIC SULFONE COMPOUNDS AND METHODS OF MAKING AND USING SAME
-
The invention provides tricyclic sulfone compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity ag
- -
-
Paragraph 00168-00169
(2013/07/31)
-
- TRICYCLIC SULFONAMIDE COMPOUNDS AND METHODS OF MAKING AND USING SAME
-
The invention provides tricyclic sulfonamide compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activit
- -
-
Paragraph 00169; 00170
(2013/07/31)
-
- Non-Pd transition metal-catalyzed hydrostannations: Bu3SnF/PMHS as a tin hydride source
-
Molybdenum, cobalt, nickel, ruthenium, and rhodium catalyzed alkyne hydrostannations using in situ generated Bu3SnH were studied. In most cases, Bu3SnF+polymethylhydrosiloxane (PMHS) performed well as the in situ source of Bu3/
- Maleczka Jr., Robert E.,Ghosh, Banibrata,Gallagher, William P.,Baker, Aaron J.,Muchnij, Jill A.,Szymanski, Amy L.
-
p. 4000 - 4008
(2013/06/27)
-
- Combinatorial synthesis of labelled drugs and PET tracers: Synthesis of a focused library of 11C-carbonyl-labelled acrylamides as potential biomarkers of EGFR expression
-
Combinatorial synthesis is extensively used in drug development and lead optimisation. However, this approach has rarely been used for positron emission tomography because of limitations in available technologies. [ 11C]Carbon monoxide is amenable to combinatorial synthesis in transition-metal-catalysed reactions because it can react with a wide variety of electrophiles and nucleophiles, which opens up the possibilities for combinatorial radiochemistry. Herein, we exemplify the combinatorial approach by 11C-labelling a library of epidermal growth factor receptor inhibitors. The selection of candidates was guided by molecular docking. Epidermal growth factor receptor is overexpressed in a variety of tumours, and it has become an important drug target. The 11C-labelling reactions were performed using four substituted vinyl iodides and three different 4-anilino-6-aminoquinazolines using a palladium-mediated reaction with [ 11C]carbon monoxide using a single set of reaction conditions. In total, 12 labelled acrylamide derivatives were radiolabelled and obtained in 24-61% decay-corrected radiochemical yield (from [11C]carbon monoxide). Starting from 5.6 GBq [11C]carbon monoxide, 0.85 GBq of formulated N-[4-(3-bromo-phenylamino)-quinazolin-6-yl]-acryl[ 11C]amide [11C]12da was obtained within 47 min from end of bombardment (specific activity of 60 GBq μmol-1). This strategy is an example of how [11C]carbon monoxide can be utilised in the labelling of libraries of drug candidates and positron emission tomography tracers for in vitro and in vivo testing. Copyright
- ?berg, Ola,L?ngstr?ma, Bengt
-
p. 477 - 483
(2013/03/28)
-
- Efficient synthesis of diverse hetero-bis-metallated alkenes as modular reagents towards highly conjugated and isolated olefinic systems
-
An efficient synthesis of diverse hetero-bis-metallated alkenes with conjugated and isolated olefin subunits is reported. Relying on those useful tin/boron reagents a convergent, palladium-catalyzed fragment coupling strategy has been developed as an eleg
- Altendorfer, Mario,Menche, Dirk
-
p. 8267 - 8269
(2012/09/21)
-
- TRICYCLIC COMPOUNDS AND METHDS OF MAKING AND USING SAME
-
The invention provides tricyclic compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against me
- -
-
Page/Page column 67
(2012/02/05)
-
- TRICYCLIC SULFONAMIDE COMPOUNDS AND METHODS OF MAKING AND USING SAME
-
The invention provides tricyclic sulfonamide compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2.
- -
-
Page/Page column 64
(2012/12/13)
-
- PARTIALLY SATURATED TRICYCLIC COMPOUNDS AND METHODS OF MAKING AND USING SAME
-
The invention provides tricyclic compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2.
- -
-
Page/Page column 118; 119
(2012/12/13)
-
- TRICYCLIC PYRAZOLE SULFONAMIDE COMPOUNDS AND METHODS OF MAKING AND USING SAME
-
The invention provides tricyclic sulfonamide compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2.
- -
-
Page/Page column 73-74
(2012/12/13)
-
- 2-PHENYL-4-CYCLOPROPYL-PYRIMIDINE DERIVATIVES
-
The present invention relates to 2-phenyl-4-cyclopropyl-pyrimidine derivatives and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular a
- -
-
Page/Page column 8
(2011/02/25)
-
- SUBSTITUTED 2-PHENYL-PYRIDINE DERIVATIVES
-
The present invention relates to compounds of formula I wherein R1, R2, R4, R5, Ra, Rb, n, W and Z are as defined in the application, their preparation and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals.
- -
-
Page/Page column 26
(2011/04/14)
-
- THIAZOLE DERIVATIVES AND THEIR USE AS P2Y12 RECEPTOR ANTAGONISTS
-
The present invention relates to thiazole derivatives of Formula (I) and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cere
- -
-
Page/Page column 56
(2010/11/05)
-
- THERAPEUTIC COMPOUNDS
-
The invention relates to novel resolvin compounds and pharmaceutical preparations thereof. The invention further relates to methods of treatment using the novel resolvin compounds of the invention.
- -
-
Page/Page column 152-153
(2010/04/27)
-
- PHOSPHONIC ACID DERIVATES AND THEIR USE AS P2Y12 RECEPTOR ANTAGONISTS
-
The invention relates to 2-phenyl-pyrimidine derivatives containing a phosphonic acid motif and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals. (I).
- -
-
Page/Page column 97
(2009/07/03)
-
- SUBSTITUTED 2-PHENYL-PYRIDINE DERIVATIVES
-
The present invention relates to compounds of formula (I) wherein R1, R2, R4, R5, Ra, Rb, n, W and Z are as defined in the application, their preparation and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals.
- -
-
Page/Page column 64-65
(2009/11/29)
-
- 2-PHENYL-4-CYCLOPROPYL-PYRIMIDINE DERIVATIVES
-
The present invention relates to 2-phenyl-4-cyclopropyl-pyrimidine derivatives and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular a
- -
-
Page/Page column 20
(2009/11/29)
-
- 2-AMINOCARBONYL-PYRIDINE DERIVATIVES
-
The present invention relates to 2-aminocarbonyl-pyridine derivatives and their use as P2Yi2 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals.
- -
-
Page/Page column 92
(2008/06/13)
-
- Compounds and amyloid probes thereof for therapeutic and imaging uses
-
The present invention provides compounds and amyloid probes thereof that allow for an antemortem method of diagnosing AD and quantitating the extent or progression of amyloid deposits (plaques) by in vivo imaging of amyloid and/or amyloid deposits in the
- -
-
Page/Page column 36; 37
(2008/06/13)
-
- Stereochemistry of contiguous cyclopropane formation from cascade cyclization of a skipped dienyl homoallyl triflate
-
Solvolysis of asymmetric homoallylic triflates bearing a terminal stannyl substituent gives disubstituted cyclopropanes and bicyclopropanes bearing differentiated termini in high enantiopurity.
- Lincoln, Christopher M.,White, James D.,Yokochi, Alexandre F. T.
-
p. 2846 - 2847
(2008/10/09)
-
- Synthesis and destannylation of η3-1-stannylallylpalladium(II) complexes
-
Reaction of 1-tributylstannyl-3-chloropropene with a Pd(PPh3) species, generated in situ from Pd2(dba)3 and two equivalents of PPh3, afforded Pd(η3-Bu3SnCHCHCH2)Cl(PPh3) (1). Complex 1 underwent PPh3 promoted protodestannylation with acetic acid or diethyl malonate to give an unsubstituted η3-allylpalladium moiety as either a detectable product or a reaction intermediate. The reaction of 1 with PPh3 and 0.5 equivalent of PdCl2(PhCN)2 afforded the dinuclear complex (μ-1-3-η3:4-6-η3-CH2CHCHCHCHCH 2){PdCl(PPh3)}2 (4) containing a hexatriene ligand, a formal vinylcarbene dimer.
- Nishida, Takuma,Watanabe, Saisuke,Yoshida, Tomohiro,Ogoshi, Sensuke,Murahashi, Tetsuro,Kurosawa, Hideo
-
-
- Derivatives of 2-[3-phenyl-2-propenyl]-1,2,3,4-tetrahydro isoquinoline, their process and their use as fungicides
-
Derivatives of 2-[3-phenyl-2-propenyl]-1,2,3,4-tetrahydro-isoquinoline compounds of the formula in all their possible stereoisomer forms as well as their mixtures wherein X is nitrogen or -CH=, R1, R2, -R3, R4, R5, R6 are individually selected from the gr
- -
-
-
- Inactivation of Medium-Chain Acyl-CoA Dehydrogenase by a Metabolite of Hypoglycin: Characterization of the Major Turnover Product and Evidence Suggesting an Alternative Flavin Modification Pathway
-
Medium-chain acyl-CoA dehydrogenase (MCAD) is a FAD-dependent enzyme that catalyzes the first step of the fatty acid oxidation cycle.When MCAD is exposed to (methylenecyclopropyl)acetyl-CoA (MCPA-CoA), a metabolite of hypoglycin A and the causative agent of Jamaican vomiting sickness, time-dependent inactivation follows with concomitant bleaching of the active-site FAD.Earlier studies have led to the postulation that the inactivation may involve a spontaneous ring fragmentation induced by a transient α-cyclopropyl radical, and thus suggest a one-electron oxidation pathway.In an effort to find more evidence for the proposed mechanism, we have isolated and characterized the major turnover product, a CoA ester consisting of a disubstituted terminal olefin, an epoxide, and a hydroxymethyl group, from the aerobic incubation mixture of MCPA-CoA and MCAD.Formation of this product may be initiated by trapping the acyclic radical intermediate with O2 to form a transient peroxy radical which, upon receiving one electron from flavin semiquinone followed by an intramolecular epoxidation, gives rise to the observed turnover product.The identification of such a highly oxygenated species as the major turnover product strongly sustains the intermediacy of a ring-opened radical, and as such, the departure from the expected inactivation may directly result from trapping of this radical intermediate by O2.This contention was subsequently substantiated by observing that the partition ratio is nearly 0 under anaerobic incubation.Interestingly, further investigation of the anaerobic inhibition resulted in the discovery of a minor inactivation pathway involving covalent modification of flavin at a locus other than the isoalloxazine ring.Although the chemical nature of the new inhibitor-coenzyme adduct(s) has yet to be elucidated, a structure having MCPA-CoA linked to the N(10) ribityl side chain is appealing.The mechanistic insights derived from this study provide compelling evidence supporting our early notion that inactivation of MCAD by MCPA-CoA is likely to proceed through a radical mechanism.
- Lai, Ming-tain,Li, Ding,Oh, Eugene,Liu, Hung-wen
-
p. 1619 - 1628
(2007/10/02)
-
- Compounds having hypocholesterolemic properties
-
This invention relates to compounds which are steroidyl derivatives of 4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one and the corresponding ring-opened hydroxy acid form thereof which are useful as antihypercholesterolemic agents, to pharmaceutical compositi
- -
-
-
- Palladium(0) Catalyzed Hydrostannylation of Alkynes. Stereospecific Syn Addition of Tributyltin Hydride
-
Tetrakis(triphenylphosphine)palladium(0) catalyzes the hydrostannylation of alkynes to give vinylstannanes in excellent yields.This reaction proceeds in syn manner.
- Miyake, Hideyoshi,Yamamura, Kimiaki
-
p. 981 - 984
(2007/10/02)
-