key: cord-1023471-cbbuewyl authors: nan title: Literature Highlights in Combinatorial Science: QSAR Comb. Sci. 9/2005 date: 2005-11-22 journal: QSAR Comb Sci DOI: 10.1002/qsar.200590050 sha: e446b854bb6a8dc1193a124da495bcb684e8c242 doc_id: 1023471 cord_uid: cbbuewyl nan Significance: The pyrazolotriazinones are stable under buffered conditions, but undergo reversible aldehyde exchange at pH 4. Hence, the reaction has potential for the generation of dynamic libraries. Title: Solution-phase parallel synthesis of a 1,2,7-trialkyl-1H-imidazo[4,5-g]quinoxalin-6-ol library scaffold. Authors Significance: The title heterocycle with three points of diversity was accessed in solution-phase starting from 1,5difluoro-2,4-dinitrobenzene. A 2,500 member library was prepared. Title: Parallel synthesis of a library of acylsemicarbazides using a solution-phase one-pot method and their evaluation as crop-protection agents. Authors Significance: A 40-member acylsemicarbazide library was prepared by ring opening of 1,3,4-oxadiazole-2-one intermediates generated in situ. The library was tested in agrochemical assays. Title: Hsp90 inhibitors identified from a library of novobiocin analogues. Authors Significance: The DNA gyrase inhibitor novobiocin is a weak inhibitor of Hsp90. A library of novobiocin analogues was prepared, and a potent inhibitor of Hsp90 mediated protein folding identified. Title: Library versus library recognition and inhibition of the HIV-1 Nef allelome. Authors: Olszewski, A.; Weiss, G. A.* University of California-Irvine, USA Source: J. Am. Chem. Soc. 2005, 127, 12178 -12179 Significance: An allelome of Nef variants (~10 7 ) was generated by phage display. Functional variants were selected by binding to p53, and disruption of the binding then screened for by a guanidine library based on the batzelladine alkaloids. One of the simpler library members was capable of effective binding to the allelome and less likely to be inactive upon protein mutation. Significance: The anthracene tagged reagent was used in enantioselective crotylations. Afterwards, the product was captured onto a supported maleimide resin, and oxidative cleavage released an aldehyde for further iterative crotylation. Title: Oligosaccharide synthesis by affinity separation based on molecular recognition between podand ether and ammonium ion. Authors: Fukase, K.;* Takashina, M.; Hori, Y.; Tanaka, D.; Tanaka, K.; Kusumoto, S. Osaka University, Japan Source: Synlett 2005, 2342 -2346 Significance: A phase tagging system based on a podand ether and its recognition by a polymer-supported ammonium group is described. The podand ether is simpler to prepare than the crown ether based system previously reported by the same group. Its application in oligosaccharide synthesis is demonstrated. Title: Polymer-micelle incarcerated scandium as a polymer-supported catalyst for high-throughput organic synthesis. Authors: Takeuchi, M.; Akiyama, R.; Kobayashi, S.* University of Tokyo, Japan Source: J. Am. Chem. Soc. 2005, 127, 13096 -13097 Significance: Solvent effects were found to be critical in the microencapsulation of scandium (III) triflate. In toluene, random aggregation was observed, while in THF-cyclohexane, spherical micelles were formed. The latter were used as catalysts in Mukaiyama aldol, Mannich and Michael reactions. The catalysts can be reused without significant leaching of scandium. Title: Solid/solution-phase annulation reagents: Single-step synthesis of cyclic amine derivatives. Authors Significance: A series of solution and solid-phase reagents are described that enable the single-step conversion of a primary amine into a cyclic derivative. For example, the imobilized bromobenzyl esters react with an amine via cyclative cleavage to release the nitrogen heterocycle. Significance: Peptide synthesis was carried out on a silicon chip with 1024 individually addressable platinum electrodes. The synthesis used Boc amine protecting groups, which were cleaved by acid electrochemically generated by the oxidation of hydrazines to azo compounds. Title: Facile preparation of carbohydrate microarrays by site-specific, covalent immobilization of unmodified carbohydrates on hydrazide-coated glass slides. Authors Significance: An array of Ugi products was prepared on planar cellulose support, under aqueous microwave assisted reaction conditions. Title: A facile solid-phase synthesis of 1,2,4,5-tetrasubstituted imidazoles using sodium benzenesulfinate as a traceless linker. Authors: Li, Wei.; Lam, Y.* National University of Singapore, Singapore Source: J. Comb. Chem. 2005, 7, 644 -647 Significance: Condensation between an immobilized sulfinic acid with an aldehyde and amide gave a sulfonylamide intermediate. Subsequent benzoin-type reaction released an a-ketoamide. Under inert atmosphere, this was cyclized to an imidazole with ammonium acetate, while reactions with triphenylphosphine or Lawessons reagent respectively yielded oxazoles and thiazoles. Title: Solid-phase synthesis of 3,4-dihydro-1H-pyrimidine-2-ones using sodium benzenesulfinate as a traceless linker. Authors: Li, W.; Lam, Y.* National University of Singapore, Singapore Source: J. Comb. Chem. 2005, 7, 721 -725 Significance: The sulfinic acid was condensed with an aldehyde and either urea or thiourea to give an immobilized sulfonylurea. Cyclization with a 1,3-dicarbonyl and dehydration provided an entry to pyrimidinones. Title: Traceless solid-phase synthesis of N1,N7-disubstituted purines. Authors: Fu, H.; Lam, Y.* National University of Singapore, Singapore Source: J. Comb. Chem. 2005, 7, 734 -738 Significance: The REM resin was alkylated with a chloropurine. The chloride was then hydrolysed, and two alkylations carried out before retro-Michael cleavage from the linker. Title: Solid-phase synthesis of 1,2-diheterocyclic-substituted (E)-olefins from a supported selenium resin. Authors Significance: A selenide resin was propargylated, followed by 1,3-dipolar cycloaddition with an organic azide generated in situ. The selenide was then alkylated with an allylic bromide and a second dipolar cycloaddition with a nitrile oxide. Oxidative cleavage from the resin then releases the bisheterocycle. Title: An efficient synthesis of carlosic acid and other 5carboxymethyltetronates from malates. Authors: Schobert, R.;* Jagusch, C. Bayreuth University, Germany Source: Synthesis 2005, 2421 -2425 Significance: A domino addition-Wittig alkenation reaction with Ph 3 PCCO was the pivotal step in the synthesis of the title compounds. The solid-phase variant featured an immobilized malate. Title: Amino acid bromides: their utilization for difficult couplings in solid-phase peptide synthesis. Authors Significance: Optimized conditions were developed for solid-phase b-peptide synthesis using Fmoc-b-amino acid monomers. To ensure functionalization of the bead interior, couplings and deprotections were carried out with cycles of 2 minute microwave irradiation (6 cycles for coupling, 3 for deprotection) and LiCl added to break down aggregation. A 100 member library was prepared. Title: A positional scanning approach to the discovery of dipeptide-based catalysts for the enantioselective addition of vinylzinc reagents to aldehydes. Significance: A set of dipeptides were prepared by solidphase synthesis and evaluated as catalysts for vinylzinc addition to aldehydes. Positional scanning enabled the identification of the optimised catalyst shown, which gave products with high enantioselectivity. Title: Efficient solid-phase-based total synthesis of the bisintercalator TANDEM. Authors Significance: An N-demethylated analogue of the natural product triostin A was synthesized and its DNA binding properties evaluated. The route involved solid-phase synthesis of a linear depsipeptide, formation of a disulfide bridge, followed by cleavage and macrolactamization in solutionphase. Title: Synthesis of oxytocin analogues with replacement of sulfur by carbon gives potent antagonists with increased stability. Authors Significance: A series of oxytocin analogues was prepared in which the disulfide bridge was replaced by an all-carbon linker. The synthesis was carried out on solid-phase, using ring-closing metathesis for macrocyclization. Both the alkene and alkane linkers (obtained by hydrogenation) were evaluated. The analogue shown is an oxytocin antagonist with improved half-life over atosiban. Title: A combinatorial approach toward the generation of ambiphilic peptide-based inhibitors of protein:geranylgeranyl Transferase-1. Significance: A genetic algorithm approach was taken to identify peptide inhibitors of GGtransferase. In the first round, 30 ambiphilic tetrapeptides were prepared and screened for activity. The 16 most potent compounds were selected, and in the second round an arbitrarily chosen building block is substituted. After five generations, low micromolar inhibitors such as the peptide shown were identified Significance: A 10-mer overlapping peptide library, prepared by IRORI tagging, was employed in the identification of epitopes from the structural proteins of the SARSassociated coronavirus Title: Discovery of a potent and selective 5-ht 5A receptor antagonist by high-throughput chemistry Significance: Lead optimisation of biphenylmethylamines was accomplished by a solid-phase route involving reductive alkylation, Suzuki cross-coupling, and acylation reactions Solid-phase synthesis and anti-infective activity of a combinatorial library based on the natural product anisomycin. Authors Significance: A library of over 8,000 anisomycin analogues was prepared by solid-phase synthesis. Compounds with antimicrobial activity and reduced cytotoxicity relative to the natural product were identified