- Synthesis of a truncated tetradenolide
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The enantiopure synthesis of a truncated tetradenolide is presented. Starting from the versatile Chiron 7,3-lactone-xylofuranose derivative (7,3-LXF), the enantiomerically pure synthesis of the title compound is obtained in six steps with a 40% overall yield.
- Dávila García, álvaro,Bernès, Sylvain,Sartillo-Piscil, Fernando,Meza-León, Rosa Luisa
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- Synthesis and biological evaluation of 1,5-dideoxy-1,5-iminoxylitol-Aamino acid hybrids as xylosidase inhibitors
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1,5-Dideoxy-1,5-iminoxylitolamino acid hybrids have been synthesized by cyclisation via a double reductive amination of xylo-pentodialdose and the respective amino groups of lysine as well as serine components. Further modification with aromatic substituents gave access to lipophilic derivatives. Kinetic studies revealed that all compounds exhibited better inhibitory properties against β-xylosidase from Thermoanaerobacterium sacharolyticum than the parent iminosugar.
- Steiner, Andreas J.,Stuetz, Arnold E.,Tarling, Chris A.,Withers, Stephen G.,Wrodnigg, Tanja M.
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Read Online
- Asymmetric synthesis and biological evaluation of (+)-cardiobutanolide, (?)-3-deoxycardiobutanolide and analogues as antiproliferative agents
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Two natural products, (+)-cardiobutanolide and (?)-3-deoxycardiobutanolide, as well as five new analogues, were synthesized in several steps that included zinc-mediated THF ring opening, subsequent stereoselective olefination, and final Sharpless asymmetric dihydroxylation. In vitro antitumour activities of these compounds were evaluated against a panel of eight human tumour cell lines and one normal cell line. Some of compounds displayed powerful effects against tumour cells, but none of them were active toward normal cells. A SAR study revealed that the change of configuration at the C-6 and C-7 position of (+)-cardiobutanolide decreases antitumour activity of analogues. It also appears that the presence of a hydroxyl group at the C-3 position increases the activity of this type of lactones. A comparison of activities of conformationally rigid lactone goniofufurone with that of more flexible cardiobutanolide and 3-deoxycardiobutanolide indicates that steric flexibility has a positive effect on cytotoxicity. It was also confirmed that removal of the phenyl group may result in analogues of higher activity. Flow cytometry analysis revealed that the synthesized compounds did not induce apoptosis and necrosis of K562 cells. However, Western blot analysis showed that all compounds but one had an increased Bax/Bcl-2 protein expression ratio.
- Kova?evi?, Ivana,Kesi?, Jelena,Popsavin, Mirjana,Francuz, Jovana,Koji?, Vesna,Jakimov, Dimitar,Rodi?, Marko V.,Zelenovi?, Bojana Sre?o,Benedekovi?, Goran,Popsavin, Velimir
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supporting information
(2021/08/30)
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- Method for preparing eribulin and intermediate thereof
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The present invention relates to a method for preparing eribulin and an intermediate thereof. In particular, the invention relates to a method for preparing a compound of formula 5, R3 is selected from aldehyde or OR1, n=0 or 1, R1 is a hydroxy protecting group, and preferably the hydroxy protecting group is selected from tert-butyldimethylsilyl, tert-butyldiphenylsilyl, p-methoxybenzyl or benzyl.The invention also provides a method for preparing halichondrin and derivatives thereof such as the eribulin from the compound of formula 5.
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Paragraph 0128-0130
(2018/09/08)
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- Thermal and Lewis acid promoted intramolecular Diels-Alder reaction of furanose tethered 1,3,9-decatriene systems: A synthetic and computational investigation
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The intramolecular Diels-Alder (IMDA) reaction of furanose tethered 1,3,9-decatrienes (4a-4r) was investigated under thermal conditions and in the presence of a Lewis acid. The stereoselectivity was determined by establishing the structures of adducts through single crystal X-ray diffraction and 1H NMR spectroscopy. It was found that contrary to expectations, the thermal IMDA reaction of (3E) and (3Z)-1,3,9-decatrienes proceeded with nearly equal rate and furnished IMDA adducts (6-25) with moderate stereoselectivity. In some cases, rearranged products (9, 12, 17 and 24) arising out of a 1,5-sigmatropic shift, cis-trans isomerization followed by IMDA reaction were formed. In contrast, a Lewis acid promoted IMDA reaction afforded only one adduct albeit in lower yields. Not surprisingly, cis-boat transition states were favored over trans-boat transition states. Experimental results were corroborated with transition state modeling of these reactions by applying density functional theory based electronic structure calculations.
- Kalmode, Hanuman P.,Maity, Dilip K.,Bhate, Prakash M.
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p. 63445 - 63462
(2016/07/19)
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- General Homologation Strategy for Synthesis of l -glycero- and d -glycero-Heptopyranoses
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A general and stereospecific homologation strategy for the synthesis of heptopyranosides is reported. The strategy employs the Wittig olefination and proline-catalyzed α-aminoxylation to achieve one carbon elongation and stereoselective hydroxylation at the C6 position, respectively. The l-glycero- and d-glycero-heptopyranosides can be obtained with nearly perfect stereoselectivity. Further study reveals the difference in the chemical shift of the C6 proton of l/d-glycero-heptopyranosyl diastereomers, which is found to be useful for assignment of the configuration of heptopyranosides.
- Mulani, Shaheen K.,Cheng, Kuang-Chun,Mong, Kwok-Kong T.
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supporting information
p. 5536 - 5539
(2015/12/01)
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- Conformationally constrained goniofufurone mimics as inhibitors of tumour cells growth: Design, synthesis and SAR study
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Synthesis of conformationally restricted (+)-goniofufurone (1) and 7-epi-(+)-goniofufurone (2) analogues, with embedded O-isopropylidene, O-methylidene or cyclic carbonate functions is disclosed starting from d-glucose. A number of potential bioisosteres
- Benedekovi?, Goran,Francuz, Jovana,Kova?evi?, Ivana,Popsavin, Mirjana,Sre?o Zelenovi?, Bojana,Koji?, Vesna,Bogdanovi?, Gordana,Divjakovi?, Vladimir,Popsavin, Velimir
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supporting information
p. 449 - 458
(2014/07/07)
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- Regioselective epoxide opening of epoxyamides derived from d-glucose. Cyclization approaches to azepanes
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Epoxyamides obtained from d-glucose have been evaluated as tools to obtain polyhydroxyazepanes. The stereoselectivity in formation of the epoxyamides was proven to be dependent of the protecting group. The conversion of epoxyamides into epoxyalcohols was
- O?a, Noe,Romero-Carrasco, Antonio,Pino-González, M. Soledad
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p. 156 - 163
(2013/04/10)
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- Total synthesis of herbicidin C and aureonuclemycin: Impasses and new avenues
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The undecose nucleoside antibiotics herbicidin C and aureonuclemycin are biologically highly active and represent challenging targets for total synthesis. Herein, the gradual evolution of our synthetic strategy toward these natural products is described in detail. The initial route encompasses metalate addition chemistry but suffers from poor stereochemical control. In contrast, the ultimately successful strategy benefits from a variety of reagent-controlled stereoselective transformations, including a surprisingly facile and highly diastereoselective N-glycosylation process. The presented work also describes new building blocks that might find further application in carbohydrate chemistry.
- Hager, Dominik,Paulitz, Christian,Tiebes, Joerg,Mayer, Peter,Trauner, Dirk
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p. 10784 - 10801
(2013/11/19)
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- Lewis acid-assisted olefin cross-metathesis reaction: An efficient approach for the synthesis of glycosidic-pyrroloquinolinone based novel building blocks of camptothecin and evaluation of their antitumor activity
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A series of glycosidic-pyrroloquinolinone based novel building blocks of camptothecin (2a-g) were synthesized via Lewis acid-assisted olefin cross-metathesis reaction using Ti(OiPr)4 30 mol % and 10 mol % of Grubb's second generation catalyst with good to excellent yields. Most of these compounds exhibited significant growth inhibitory effects on all the tested cancer cell lines and three compounds (2c, 2d and 2e) showed potent cytotoxic activity.
- Nagarapu, Lingaiah,Gaikwad, Hanmant K.,Bantu, Rajashaker,Ganesh Kumar,Pombala, Sujitha
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supporting information; scheme or table
p. 1287 - 1291
(2012/03/27)
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- Intramolecular cyclization of alkoxyaminosugars: Access to novel glycosidase inhibitor families
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We report the synthesis of two novel families of iminosugars as glycosidase inhibitors involving an intramolecular cyclization between an N-alkoxyamino group and a latent aldehyde of a reducing sugar as the key step. Using this methodology we have prepare
- Martínez-Castro, Elisa,González-Benjumea, Alejandro,López, óscar,Maya, Inés,álvarez, Eleuterio,Fernández-Bola?os, José G.
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scheme or table
p. 4220 - 4228
(2012/07/14)
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- Selective Wittig olefination in aqueous media for the rapid preparation of unsaturated 7,3-lactone-α-d-xylofuranose derivatives
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A highly efficient and rapid protocol for the preparation of the title compounds 1a and 1b from d-glucose derivatives 2a and 2b, respectively, is reported. To this end, highly selective Wittig olefination in aqueous media was developed for the elaboration
- Ramirez, Elsie,Sánchez, Mario,Meza-León, Rosa L.,Quintero, Leticia,Sartillo-Piscil, Fernando
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supporting information; experimental part
p. 2178 - 2180
(2010/06/14)
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- Divergent synthesis of cytotoxic styryl lactones isolated from Polyalthia crassa. The first total synthesis of crassalactone B
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The first total synthesis of (+)-crassalactone B (2) and a new syntheses of (+)-crassalactone C (3) has been achieved starting from d-glucose. The natural products 2 and 3 can be selectively accessed by changing the conditions for TBDPS cleavage in the fi
- Popsavin, Velimir,Benedekovi?, Goran,Popsavin, Mirjana,Koji?, Vesna,Bogdanovi?, Gordana
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scheme or table
p. 3426 - 3429
(2010/08/22)
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- Stereodivergent access to polyhydroxylated 10-azabicyclo[4.3.1]decanes as new calystegine analogues
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A rapid and stereodivergent access to polyhydroxylated 10- azabicyclo[4.3.1]decanes as new calystegine analogues by way of a double benzotriazolyl/carbon nucleophile exchange followed by a ring-closing metathesis was achieved. Preliminary evaluation of the new compounds as glucocerebrosidase inhibitors was also performed.
- Chagnault, Vincent,Compain, Philippe,Lewinski, Krzysztof,Ikeda, Kyoko,Asano, Naoki,Martin, Olivier R.
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supporting information; experimental part
p. 3179 - 3182
(2009/09/05)
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- Six-membered ring phosphates and phosphonates as model compounds for cyclic phosphate prodrugs: Is the anomeric effect involved in the selective and spontaneous cleavage of cyclic phosphate prodrugs?
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(Chemical Equation Presented) In recent years, several six-membered ring phosph(on)ates and phosphonamides have been reported as potent prodrugs against liver diseases such as hepatitis B and C and also as antitumor agents. Apparently, the success for the
- Cruz-Gregorio, Silvano,Rodriguez-Palacios, Vicente,H?pfl, Herbert,Quintero, Leticia,Sartillo-Piscil, Fernando
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supporting information; experimental part
p. 197 - 205
(2009/04/10)
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- Iminosugar glycoconjugates
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The iminosugar conjugates according to the invention are N-alkylated 1,5-dideoxy-1,5-iminohexitol or 1,5-dideoxy-1,5-iminopentitol derivatives. The iminosugar component can be, for example, D-gluco-, L-ido-, D-galacto-, D-manno-, 2-acetamido-2-deoxy-D-gluco- or xylo-configuration. The N-substituent is a protected L-α-aminoacid derivative, showing L-lysine-like structural features. The linkage between the carbohydrate and the peptide component is not via the usual glycosidic position, but shows structural features of a very stable tertiary amine. Thus the linkage is very stable. These new compounds are synthesised by using catalytic intramolecular reductive amination of dicarbonyl sugars with partially protected amino acids. The process of intramolecular reductive amination itself is carried out using Pearlman's catalyst (Pd(OH)2/C) and H2 at ambient pressure and room temperature. The resulting accessible class of iminosugar conjugate compounds is represented by the general structure shown in Figure 4(c). The alkyl chain length parameter n can be freely chosen from n=0 upwards. Preferably n is between 0 and 10, and more preferably n is 2, 3, or 4. Residue R1 can be chosen from H, OH, or NHAc, with Ac being Acetyl. R2 can be H, OH, or NHAc. R3, R4, R5, R6 can be H or OH. R7 and R8 can be H, CH2OH CH3, COQH, or COOR with R being Alkyl or Aryl. R9 and R10 can be chosen from H, NH2, NHR, with R being a protective group, an amino acid, a peptide, or a protein. R11 can be OH, O-Alkyl, O-Aryl, NH2, N-Alkyl, N-Aryl, amino acid or peptide, connected via an amide bond.
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Page/Page column 6-7
(2008/06/13)
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- Concise synthesis of enantiomers of 4-aminobutane-1,2,3-triol
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(Chemical Equation Presented) A very efficient synthesis of (2R,3S) and (2S,3R)-4-aminobutane-1,2,3-triol has been developed using either D- or L-glucose as the starting material. A key step is the one-pot conversion of an aldehyde to an amide, the scope of which has been extended to include other carbohydrate-derived aldehydes.
- Dunlap, Norma K.,Drake, John,Ward, Andrea,Salyard, Tracy L. J.,Martin, Leah
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p. 2928 - 2930
(2008/09/19)
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- Deoxygenation of 5-O-benzoyl-1,2-isopropylidene-3-O-imidazolylthiocarbonyl-α-d-xylofuranose using dimethyl phosphite: an efficient alternate method towards a 3′-deoxynucleoside glycosyl donor
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An efficient radical deoxygenation reaction of thiocarbonylimidazolyl activated glycoside analogue using dimethyl phosphite as hydrogen source and radical chain carrier was performed as a key step in a multi step synthesis towards a common 3-deoxy glycosyl donor for 3′-deoxynucleosides. This method has safety and cost advantages compared to the generally used radical reduction reagents.
- Zlatev, Ivan,Vasseur, Jean-Jacques,Morvan, Fran?ois
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p. 3288 - 3290
(2008/09/20)
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- Rhodium-catalyzed decarbonylation of aldoses
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(Chemical Equation Presented) A catalytic procedure is described for decarbonylation of unprotected aldoses to afford alditols with one less carbon atom. The reaction is performed with the rhodium complex Rh(dppp)2Cl in a refluxing diglyme-DMA solution. A slightly improved catalyst turnover is observed when a catalytic amount of pyridine is added. Under these conditions most hexoses and pentoses undergo decarbonylation into the corresponding pentitols and tetrols in isolated yields around 70%. The reaction has been applied as the key transformation in a five-step synthesis of L-threose from D-glucose.
- Monrad, Rune Nygaard,Madsen, Robert
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p. 9782 - 9785
(2008/03/17)
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- Chiron approach for the synthesis of (1S,2R,5R,7S)-2-hydroxy-exo-brevicomin
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(1S,2R,5R,7S)-2-Hydroxy-exo-brevicomin ent-1 was synthesized from 1,2;5,6-di-O-isopropylidene-d-glucose in seven steps. The key reaction in our synthesis is the formation of bicyclic ketal 7 under acid mediated acetal exchange of a 1,2-acetonide of d-glucose derivative 6.
- Gautam,Kumar, D. Naveen,Rao, B. Venkateswara
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p. 819 - 821
(2007/10/03)
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- Nucleoside synthesis from 3-alkylated sugars: Role of 3β-oxy substituents in directing nucleoside formation
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Using Vorbrueggen's protocol, reaction of persilylated uracil with xylofuranose derivatives having 3β-oxy-3α-alkyl substitution produced both α- and β-nucleosides. Only the β-nucleosides were formed from substrates having the reverse stereochemistry at C-3 or lacking the 3-alkyl substituent. Participation of the 3β-oxy substituent in stabilizing the incipient C-1 carbonium ion (or oxonium ion) intermediate has been suggested from analysis of energy-minimized conformations. The Royal Society of Chemistry 2006.
- Sahabuddin, Sk.,Ghosh, Ramprasad,Achari, Basudeb,Mandal, Sukhendu B.
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p. 551 - 557
(2008/02/02)
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- Synthesis and biological evaluation of branched and conformationally restricted analogs of the anticancer compounds 3′-C-ethynyluridine (EUrd) and 3′-C-ethynylcytidine (ECyd)
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The synthesis of branched and conformationally restricted analogs of the anticancer nucleosides 3′-C-ethynyluridine (EUrd) and 3′-C- ethynylcytidine (ECyd) is presented. Molecular modeling and 1H NMR coupling constant analysis revealed that the furanose rings of all analogs except the LNA analog are conformationally biased towards South conformation, and are thus mimicking the structure of ECyd. All target nucleosides were devoid of anti-HIV or anticancer activity.
- Hrdlicka, Patrick J.,Andersen, Nicolai K.,Jepsen, Jan S.,Hansen, Flemming G.,Haselmann, Kim F.,Nielsen, Claus,Wengel, Jesper
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p. 2597 - 2621
(2007/10/03)
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- Introduction of a carbohydrate moiety into the structure of thiourea compounds targeting HIV-1 reverse transcriptase
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We developed a novel approach to introduce a carbohydrate moiety into the structure of thiourea compounds targeting the NNI binding pocket of the HIV-1 reverse transcriptase. The described method involves the synthesis of an amino-substituted carbohydrate moiety which is then condensed with various thiocarbonylimidazole derivatives of substituted aromatic amines.
- Goud, P. Mallikarjun,Venkatachalam,Uckun
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p. 1185 - 1193
(2007/10/03)
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- Study of stereoselectivity in organometallic additions to 1,2-O-isopropylidene-O-R-α-D-xylopentodialdo-1,4-furanose
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Diastereofacial selectivity of the addition of organometallic reagents to 1,2-O-isopropylidene-O-R-α-D-xylopentodialdo-44-furanose (6) was studied.
- Gracza, Tibor,Szolcsanyi, Peter
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p. 1386 - 1398
(2007/10/03)
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- Synthesis of an enantiomeric 2,5-di-(E)-propenyltetrahydrofuran-3,4-diol derivative
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For total synthesis of a novel bioactive δ-lactone antibiotic FD-211, a key intermediate, a 2,5-di-(E)-propenyltetrahydrofuran-3,4-diol derivative, was synthesized from diacetone D-glucose.
- Suzuki, Eiju,Takao, Ken-Ichi,Tadano, Kin-Ichi
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p. 519 - 523
(2007/10/03)
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- Application of the reaction of D-glucose with meldrum's acid: Total synthesis of the styryl lactones (+)-goniofufurone and (+)-7-epi- goniofufurone
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The syntheses of the styryl lactones (+)-goniofufurone (1) and (+)-7- epi-goniofufurone (2) from D-glucose are presented. The key steps are the formation of the lactone moiety by reaction of the hemiacetals 15 and 16 with meldrum's acid (3) and the addition of phenylmagnesium bromide to the aldehydes 9 or 12. In the last case, we obtained the L-ido and D-gluco configurated products 13 and 14 in a 3:1 mixture. However, addition of ZnCl2 shifted the diastereomeric ratio towards the desired compound 14.
- Bruns, Rainer,Wernicke, Angelika,Koell, Peter
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p. 9793 - 9800
(2007/10/03)
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- A concise synthesis of harzialactone A from D-glucose and revision of absolute stereochemistry
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Synthesis of 2 by a chiron approach is described starting from monoacetone-D-glucose 4. Absolute stereochemistry of natural harzialactone A 1 (2S,4S) is revised to 2 (2R,4R).
- Mereyala, Hari Babu
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p. 2305 - 2306
(2007/10/03)
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- Reversible charge-accelerated oxy-cope rearrangements
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An asymmetric synthesis of the oxetane-containing norbornanone 23 and its coupling to trans-1-propenyllithium to give 24 are reported, in tandem with the preparation of the related alcohols 28 and 30. All three divinyl carbinols undergo anionic oxy-Cope rearrangement very rapidly at low temperature. Quenching of 24-K+ and 28-K+ under these conditions with water or various aqueous salt solutions results in protonation of the alkoxides. If these reaction mixtures are poured instead onto cold (O °C) silica gel, their sigmatropically related ketones are isolated in very good yield. Whereas the 24-K+?25-K+ equilibrium pair is not reactive to molecular oxygen, 30-K+ is directly converted into an α-hydroperoxy ketone under comparable conditions. These and additional observations are rationalized in the context of atropisomerism involving conversion of oxygen- up enolates, formed reversibly under kinetically controlled conditions, into their thermodynamically favored, more reactive oxygen-down conformers.
- Tsui, Hon-Chung,Paquette, Leo A.
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p. 9968 - 9977
(2007/10/03)
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- Stable, isotopically substituted carbohydrates: an improved synthesis of (6-13C)aldohexoses.
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1,2-O-Isopropylidene-alpha-D-xylo-pentodialdo-1,4-furanose (1) has been used as the parent aldose in the preparation of D-(6-13C)glucose and L-6-13C)idose via cyanohydrin reduction. The addition of K13CN (pH 6.8, 5 min) to 1 yields D-gluco and L-ido cyanohydrins that are readily reduced with H2 and Pd-BaSO4, to give 1,2-O-isopropylidene-alpha-D-gluco-hexodialdo-1,4-furanose (2; approximately 65%) and 1,2-O-isopropylidene-beta-L-ido-hexodialdo-1,4-furanose (3; 35%). Aldehydes 2 and 3 are reduced in situ with NaBH4, the resulting alcohols are deprotected with aqueous acid, and the aldoses are chromatographed on Dowex 50 X-8 (Ca2+) ion-exchange resin (200-400 mesh), to yield D-(6-13C)glucose (6) and L-(6-13C)idose (7). Molybdate epimerization of 6 and 7 yields D-(6-13C)mannose and L-(6-13C)gulose, respectively. A similar reaction scheme may be applied to methyl 2,3-O-isopropylidene-beta-D-ribo-pentodialdo-1,4-furanoside to generate the remaining four (6-13C)aldohexoses. This route is considerably simpler than the traditional Kiliani-Fischer route, and higher yields are obtained.
- King-Morris,Bondo,Mrowca,Serianni
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