- Synthesis method of jatrophane type diterpene key intermediate and derivatives thereof
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The invention discloses a synthesis method of a jatrophane type diterpene key intermediate and derivatives thereof. The structural formula of the key intermediate is shown in multiple embodiments of the invention, and the jatrophane type diterpene key int
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Paragraph 0112-0113
(2021/02/06)
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- Stereoselective Construction of the Methylcyclopentane Core of Peditithins B-H with Five Continuous Stereocenters
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A stereoselective construction of the methylcyclopentane core (3) of jatrophane diterpenoids peditithins B-H was achieved in 14 steps from commercially available d-(+)-ribono-1,4-lactone (9). The linear 5-ene-heptanal derived from 9 was cyclized to the five-membered ring by an intramolecular carbonyl ene reaction, and five continuous stereocenters on 3 were stereoselectively introduced via a successive substrate-controlled manner, involving diastereoselective 1,4-addition, MoOPH-induced hydroxylation, and stereospecific epoxidation.
- Li, Qingjiang,Li, Wei,Ni, Fu-Qiang,Wu, Shu-Qi,Yin, Sheng
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supporting information
p. 9360 - 9364
(2020/12/21)
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- High-Yielding Diastereoselective syn-Dihydroxylation of Protected HBO: An Access to D-(+)-Ribono-1,4-lactone and 5-O-Protected Analogues
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A diastereoselective chemoenzymatic synthetic pathway to D-(+)-ribono-1,4-lactone, a versatile chiral sugar derivative widely used for the synthesis of various natural products, has been designed from cellulose-based levoglucosenone (LGO). This route involves a sustainable Baeyer-Villiger oxidation of LGO to produce enantiopure (S)-γ-hydroxymethyl-α,β-butenolide (HBO) that is further functionalized with various protecting groups to provide 5-O-protected γ-hydroxymethyl-α,β-butenolides. The latter then undergo a diastereoselective and high-yielding syn-dihydroxylation of the α,β-unsaturated lactone moiety followed by a deprotection step to give D-(+)-ribono-1,4-lactone. Through this 4-step synthetic route from LGO, D-(+)-ribono-1,4-lactone is obtained with d.r. varying from 82:18 to 97:3 and in overall yields between 32 and 41 % depending on the protecting group used. Moreover, valuable synthetic intermediates 5-O-tert-butyldimethylsilyl-, 5-O-tert-butyldiphenylsilyl- as well as 5-O-benzyl-ribono-1,4-lactones are obtained in 3 steps from LGO in 58, 61 and 40 %, respectively.
- Moreaux, Maxime,Bonneau, Guillaume,Peru, Aurélien,Brunissen, Fanny,Janvier, Marine,Haudrechy, Arnaud,Allais, Florent
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p. 1600 - 1604
(2019/01/14)
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- Exploring the Chemistry of Bicyclic Isoxazolidines for the Multicomponent Synthesis of Glycomimetic Building Blocks
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Starting from a chiral furanone, the nitrone-olefin [3 + 2] cycloaddition can be used to obtain bicyclic isoxazolidines for which we report a set of reactions to selectively modify each functional position. These synthetically versatile bicyclic isoxazolidines allowed us to obtain complex glycomimetic building blocks, like iminosugars, via multicomponent chemistry. For example, a library of 20 pipecolic acid derivatives, a recurring motif in various prescription drugs, could be obtained via a one-pot Staudinger/aza-Wittig/Ugi three-component reaction of a bicyclic isoxazolidine-derived azido-hemiacetal. Notably, specific pipecolic acids in this library were obtained via hydrolysis of an unique tricyclic imidate side product of the Ugi reaction. The azido-hemiacetal was also converted into an aza-C-glycoside iminosugar via an unprecendented one-pot Staudinger/aza-Wittig/Mannich reaction.
- Hoogenboom, Jorin,Lutz, Martin,Zuilhof, Han,Wennekes, Tom
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p. 8826 - 8836
(2016/10/14)
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- Synthesis and Evaluation of a 2,11-Cembranoid-Inspired Library
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The 2,11-cembranoid family of natural products has been used as inspiration for the synthesis of a structurally simplified, functionally diverse library of octahydroisobenzofuran-based compounds designed to augment a typical medicinal chemistry library screen. Ring-closing metathesis, lactonisation and SmI2-mediated methods were exemplified and applied to the installation of a third ring to mimic the nine-membered ring of the 2,11-cembranoids. The library was assessed for aqueous solubility and permeability, with a chemical-space analysis performed for comparison to the family of cembranoid natural products and a sample set of a screening library. Preliminary investigations in cancer cells showed that the simpler scaffolds could recapitulate the reported anti-migratory activity of the natural products. Building a bridge: A library of compounds based on the naturally occurring 2,11-cembranoid family has been synthesised by using different synthetic strategies. The library was found to cover the space between the natural products and a screening library sample set (see figure). The new compounds were shown to recapitulate reported activities of the natural products.
- Welford, Amanda J,Caldwell, John J.,Liu, Manjuan,Richards, Meirion,Brown, Nathan,Lomas, Cara,Tizzard, Graham J.,Pitak, Mateusz B.,Coles, Simon J.,Eccles, Suzanne A.,Raynaud, Florence I.,Collins, Ian
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supporting information
p. 5657 - 5664
(2016/04/20)
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- NOVEL 3-SUBSTITUTED 5-AMINO-6H-THIAZOLO[4,5-D]PYRIMIDINE-2,7-DIONE COMPOUNDS FOR THE TREATMENT AND PROPHYLAXIS OF VIRUS INFECTION
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The present invention relates to compounds of formula (I), wherein R1, R2 and R3 are as described herein, and their prodrugs or pharmaceutically acceptable salt, enantiomer or diastereomer thereof, and compositions including the compounds and methods of using the compounds.
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Paragraph 0592; 0595; 0596
(2016/08/07)
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- NOVEL SUBSTITUTED AMINOTHIAZOLOPYRIMIDINEDIONE FOR THE TREATMENT AND PROPHYLAXIS OF VIRUS INFECTION
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The present invention relates to compounds of formula (I), wherein R1 to R5 are as described herein, and their prodrugs or pharmaceutically acceptable salt, enantiomer or diastereomer thereof, and compositions including the compounds and methods of using the compounds.
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Page/Page column 25; 26
(2016/11/28)
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- Novel Bicyclic Pyridinones
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Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.
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Page/Page column
(2014/04/03)
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- An approach to the carbon backbone of bielschowskysin, part 1: Photocyclization strategy
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Several macrocyclization reaction attempts of highly advanced precursors toward a total synthesis of marine diterpene bielschowskysin are disclosed. Biomimetic [2+2]-photocyclization reactions were applied to construct the cyclobutane core in these intermediates, which could be accessed along scalable high-yielding reaction sequences from cheap enantiopure starting-materials. Asymmetric syntheses of various highly functionalized intermediates toward the total synthesis of bielschowskysin (1) are described. In particular a biomimetic [2+2]-photocycloaddition reaction strategy, forming the cyclobutane core, was followed by various macrocyclization reactions attempts. Copyright
- Himmelbauer, Martin,Farcet, Jean-Baptiste,Gagnepain, Julien,Mulzer, Johann
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p. 8214 - 8244
(2014/01/06)
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- Expedient pathway into optically active 2-oxopiperidines
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The piperidine ring system is one of the most common structural subunits and is found in many natural products. Moreover, piperidine alkaloids and derivatives thereof are of great interest for the pharmaceutical industry since they exhibit a wide range of
- Van Den Broek, Sebastiaan A. M. W.,Rensen, Peter G. W.,Van Delft, Floris L.,Rutjes, Floris P. J. T.
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scheme or table
p. 5906 - 5912
(2011/01/12)
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- Synthesis and anti-HIV activity of conformationally restricted bicyclic hexahydroisobenzofuran nucleoside analogs
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A chiral synthesis of a series of hexahydroisobenzofuran (HIBF) nucleosides has been accomplished via glycosylation of a stereo-defined (syn-isomer) sugar motif 16 with the appropriate silylated bases. All nucleoside analogs were obtained in 52-71% yield as a mixture of α- and β-anomeric products increasing the breadth of the novel nucleosides available for screening. The structure of the novel bicyclic HIBF nucleosides was established by a single crystal X-ray structure of the β-HIBF thymine analog 22b. Furthermore, the sugar conformation for these nucleosides was established as N-type. Among the novel HIBF nucleosides synthesized, twenty-five compounds were tested as inhibitor of HIV-1 in human peripheral blood mononuclear (PBM) cells and seven were found to be active (EC50 = 12.3-36.2 μM). Six of these compounds were purine analogs with β-HIBF inosine analog 22o being the most potent (EC50 = 12.3 μM) among all compounds tested. The striking resemblance between didanosine (ddI) and 22o may explain the potent anti-HIV activity.
- Diaz-Rodriguez, Alba,Sanghvi, Yogesh S.,Fernandez, Susana,Schinazi, Raymond F.,Theodorakis, Emmanuel A.,Ferrero, Miguel,Gotor, Vicente
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scheme or table
p. 1415 - 1423
(2009/10/24)
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- Cycloaddition and one-carbon homologation studies in the synthesis of advanced iridoid precursors
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A Diels-Alder cycloaddition approach to the sweroside aglycone intermediate of iridoids was explored using silylated butenolides and levoglucosenone as dienophiles under both Lewis acid and thermal conditions. Results of this study reveal no evidence that
- Stevens, Anne T.,Caira, Mino R.,Bull, James R.,Chibale, Kelly
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supporting information; experimental part
p. 3527 - 3536
(2010/01/06)
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- Kinetic and thermodynamic aspects in the 1,3-dipolar cycloaddition of five-membered cyclic nitrones to α,β-unsaturated γ- and δ-lactones
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The 1,3-dipolar cycloaddition of five-membered ring nitrones to the α,β-unsaturated δ-lactones is kinetically controlled, whereas the same reactions involving γ-lactones, upon heating and prolonged reaction times, display visible reversibility of the reac
- Stecko, Sebastian,Pasniczek, Konrad,Jurczak, Margarita,Urbanczyk-Lipkowska, Zofia,Chmielewski, Marek
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p. 1085 - 1093
(2008/02/08)
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- Norrisolide: Total synthesis and related studies
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A stereoselective synthesis of (+)-norrisolide is presented. This natural product belongs to a family of marine spongiane diterpenes the structure of which is characterized by a fused γ-lactone-γ-lactol ring system attached to a bicyclic hydrophobic core.
- Brady, Thomas P.,Kim, Sun Hee,Wen, Ke,Kim, Charles,Theodorakis, Emmanuel A.
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p. 7175 - 7190
(2007/10/03)
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- Controlling π-Facial Diastereoselectivity in the 1,3-Dipolar Cycloadditions of Diazomethane to Chiral Pentenoates and Furanones: Enantioselective Stereodivergent Syntheses of Cyclopropane Hydroxy Acids and Didehydro Amino Acids
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The title compounds have been synthesized in both enantiomeric forms and in good overall yields by using D-glyceraldehyde as the single chiral precursor. The efficiency and usefulness of the synthetic routes have been secured by performing controlled manipulations of the functional groups and by highly stereoselective transformations, namely Wittig-Horner condensations and cyclopropanations. Cyclopropane derivatives have been synthesized through 1,3-dipolar cycloaddition of diazomethane to chiral pentenoates or furanones obtained, in turn, from D-glyceraldehyde. Syn/ anti stereochemistry of the cycloadducts has been unequivocally assigned and rationalized. Since π-facial diastereoselectivity involved in these cycloadditions is the opposite for cyclic and open- chain structures, enantiomeric series of products can be derived.
- Martin-Vila, Marta,Hanafi, Neuh,Jimenez, Jose M.,Alvarez-Larena, Angel,Piniella, Joan F.,Branchadell, Vicenc,Oliva, Antonio,Ortuno, Rosa M.
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p. 3581 - 3589
(2007/10/03)
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- Synthetic study on gymnodimine: Highly stereoselective construction of substituted tetrahydrofuran and cyclohexene moieties
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The synthetic studies on gymnodimine, a shellfish toxin, are described. This marine toxin consists of 16-membered carbocycle, tetrahydrofuran, and spiro-imine moieties. Our synthetic strategy involves the stereoselective allylation of tetrahydrofuran compound and the exo-selective intramolecular Diels-Alder reaction.
- Ishihara, Jun,Miyakawa, Jun,Tsujimoto, Takashi,Murai, Akio
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p. 1417 - 1419
(2007/10/03)
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- A synthetic route to 3-C-alkyl (or 3-C-phenyl-) 2,3-dideoxy-D-erythro- pentono-1,4-lactones: Intermediates in the synthesis of 2(3H)-furanones
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A series of 3-C-alkyl- (and 3-C-phenyl-) 2,3-dideoxy-D-erythro-pentono- 1,4-lactones, compounds which are important in the synthesis of modified nucleosides and antibiotic sugars, were synthesized from D-ribonolactone. By a route that proceeded via 5-O-pr
- Raveendranath,Blazis,Agyei-Aye,Hebbler,Gentile,Hawkins,Johnson,Baker
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p. 207 - 223
(2007/10/02)
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- Stereoselective synthesis of 3-azido-2,3-dideoxy-D-ribose derivatives and its utilization for the synthesis of anti-HIV nucleosides [1]
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Detail account of the synthesis of 3'-azido nucleosides utilizing 3- azido-2,3-dideoxy-D-ribose derivative 7 as the key intermediate was described. The key intermediate 7 was synthesized from D-mannitol in 8 steps in a preparative scale. The Michael reaction of the azide group with α,β- unsaturated-γ-butyrolactone 4 was affected by the steric bulkiness of the substituent at the 5-O position. A bulky t-butyldiphenylsilyl substitution at 5-O gave almost exclusively the α-azido adduct 5b, while unsubstitution at 5-O produced I:1 mixture of α-and β-adducts. The ratio of α to β anomers in the condensation between azido acetate 7a and pyrimidine bases for the preparation of AZT and AZDU was greatly influenced by the solvent and the Lewis acid catalyst used. In the synthesis of 12(AZDU, CS-87), the combination of dichloroethane and trimethylsilyl triflate gave an optimal result, while in the case of 14(AZT), various conditions gave similar ratio of α,β anomers. The azido intermediate 7b was also utilized for the synthesis of several 3'-azido purine-like nucleosides 16-27. The glycosylation was also affected by the Lewis acid catalyst. Boron trifluoride etherate gave the desired N1-glycosylated compounds in which the α-anomer was major, but other catalysts such as trimethylsilyl triflate or stannic chloride produced N2-glycosylated compounds as the major products. The newly synthesized purine-like compounds have been tested against HIV, however, none of them showed any significant activity.
- Jeong,Beach,Chu
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p. 1445 - 1452
(2007/10/02)
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- DIELS-ALDER CYCLOADDITIONS OF CHIRAL BUTENOLIDES WITH BUTADIENE AND ISOPRENE: DIASTEREOFACIAL SELECTIVITY AND REGIOSELECTIVITY
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Chiral butenolides react with butandiene at 210 deg C giving optically active bicyclic compounds wiht excellent diastereoselectivity, in good yields.Optical purity of the adducts has been verified either by chemical correlation and/or by the use of Eu(hfc
- Ortuno, Rosa M.,Ballesteros, Montserrat,Corbera, Jordi,Sanchez-Ferrando, Francisco,Font, Josep
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p. 1711 - 1720
(2007/10/02)
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- STEREOCHEMICAL CONTROL OF NATURE'S BIOSYNTHETIC PATHWAYS: A GENERAL STRATEGY FOR THE SYNTHESIS OF POLYPROPIONATE-DERIVED STRUCTURAL UNITS FROM A SINGLE CHIRAL PROGENITOR
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A general strategy that permits the stereocontrolled construction of acyclic chains containing vicinal and/or alternating alkyl and hydroxy substituents is presented.Structural subunits of ionomycin were synthesized from a common chiral intermediate.
- Hanessian, S.,Murray, P. J.
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p. 5055 - 5072
(2007/10/02)
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- Chiral Oxabicyclic Systems from Ribonolactone
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We describe the synthesis of (-)-5-O-diphenyl-t-butylsiloxymethyl-5H-furan-2-one (4) from D-ribonolactone; conversion of this chiral butenolide into (+)-(1R,6S,7S)-7-diphenyl-t-butylsiloxymethyl-8-oxabicyclonon-3-en-9-one (10) (by means of a Diels-
- Drew, Michael G. B.,Mann, John,Thomas, Alison
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p. 2279 - 2286
(2007/10/02)
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- Chiral Bicycles from Ribonolactone
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The preparation of the chiral butenolide (4b) is described, together with its use in annulation reactions yielding stereochemically defined bicyclo, , and ring systems; the synthetic utility of these species is indicated.
- Mann, John,Thomas, Alison
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p. 737 - 738
(2007/10/02)
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