- Diverse synthetic approaches towards C1′-branched acyclic nucleoside phosphonates
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Acyclic nucleoside phosphonates (ANPs) represent a significant class of antiviral, anticancer, and antiprotozoal compounds. It is therefore highly desirable to have diverse synthetic routes leading towards these molecules. In the past, many structural modifications were explored, but surprisingly, the field of C1′-branched ANPs has been neglected with only a handful of articles reporting their synthesis. Herein we describe and compare five convenient approaches leading to key synthetic 6-chloropurine ANPs bearing the 9-phosphonomethoxyethyl (PME) moiety branched at the C1′ position. These intermediates can be further vastly diversified into target C1′-branched ANPs bearing either natural or unnatural nucleobases. The importance of C1′-branched ANPs is emphasized by their analogy with C1′-substituted cyclic nucleotides (such as remdesivir, a broad-spectrum antiviral agent) and evaluation of their biological activity (e.g. antiviral, antineoplastic, and antiprotozoal) will be a tempting subject of further research.
- Dra?ínsky, Martin,Janeba, Zlatko,Kal?ic, Filip
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supporting information
p. 6958 - 6963
(2021/08/25)
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- Selective hydrogenation of primary amides and cyclic di-peptides under Ru-catalysis
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A ruthenium(II)-catalyzed selective hydrogenation of challenging primary amides and cyclic di-peptides to their corresponding primary alcohols and amino alcohols, respectively, is reported. The hydrogenation reaction operates under mild and eco-benign conditions and can be scaled-up.
- Subaramanian, Murugan,Sivakumar, Ganesan,Babu, Jessin K.,Balaraman, Ekambaram
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supporting information
p. 12411 - 12414
(2020/10/30)
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- Synthesis and structure-activity relationship of a novel class of 15-membered macrolide antibiotics known as '11a-azalides'
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Macrolide antibiotics are widely prescribed for the treatment of respiratory tract infections; however, the increasing prevalence of macrolide-resistant pathogens is a public health concern. Therefore, the development of new macrolide scaffolds with activities against resistant pathogens is urgently needed. An efficient method for reconstructing the erythromycin A macrolactone skeleton has been established. Based on this methodology, novel 15-membered macrolides, known as '11a-azalides', with substituents at the C12, C13, or C4″ positions were synthesized and their antibacterial activities were evaluated. These derivatives showed promising antibacterial activities against erythromycin-resistant Streptococcus pneumoniae. Among them, the C4″ substituted derivatives had the most potent activity against erythromycin-resistant S. pneumoniae.
- Sugimoto, Tomohiro,Tanikawa, Tetsuya,Suzuki, Keiko,Yamasaki, Yukiko
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p. 5787 - 5801
(2012/11/06)
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- Synthesis and antibacterial activity of a novel class of 15-membered macrolide antibiotics, "11a-Azalides"
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An efficient method for the reconstruction of the 9-dihydroerythromycin A macrolactone skeleton has been established. The key steps are oxidative cleavage at the 11,12-position and reconstruction after insertion of an appropriate functionalized amino alcohol. Novel 15-membered macrolides, we named as "11a-azalides", were synthesized based on the above methodology and evaluated for their antibacterial activity. Among them, (13R)-benzyloxymethyl- 11a-azalide showed the most potent Streptococcus pneumoniae activity, with improved activity against a representative erythromycin-resistant strain compared to clarithromycin (CAM).
- Sugimoto, Tomohiro,Tanikawa, Tetsuya
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body text
p. 234 - 237
(2011/04/26)
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- Cyclic sulfur ylides derived from gleason-type chiral auxiliaries for the asymmetric synthesis of epoxy amides
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Gleason-type chiral auxiliaries were used for the synthesis of a novel class of sulfonium salts, obtained via methylation of the sulfide with Meerwein's salt. The salts were reacted with aldehydes under basic conditions to provide epoxy amides, which were reduced to their corresponding epoxy alcohols in excellent enantiomeric excesses. Interestingly, it was feasible to synthesize both enantiomeric epoxy alcohols depending on which of the sulfonium salts, prepared from L-amino acids (6 and 9 from L-valine or 15 and 16 from L-serine) was employed.
- Sarabia, Francisco,Vivar-Garcia, Carlos,Garcia-Castro, Miguel,Martin-Ortiz, Jorge
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experimental part
p. 3139 - 3150
(2011/06/22)
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- Synthesis of new oxathiazinane dioxides and their in vitro cancer cell growth inhibitory activity
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New oxathiazinane dioxides derived from d- and l-serine have been tested for their in vitro cell growth inhibitory activity toward SKBR3 breast cancer cells. Compound (R)-24 (R′ = BrCH2C6H 4-C6H4CH2) showed a cytotoxicity with IC50 ≈ 10 μM.
- Borcard, Fran?oise,Baud, Matthias,Bello, Claudia,Dal Bello, Giovanna,Grossi, Francesco,Pronzato, Paolo,Cea, Michele,Nencioni, Alessio,Vogel, Pierre
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supporting information; experimental part
p. 5353 - 5356
(2010/11/04)
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- NOVEL DIHYDROXYPYRROLIDINE DERIVATIVES AS ANTI-CANCER AGENTS
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The present invention provides new dihydroxypyrrolidine derivatives for use as medicaments. The compounds are useful in the treatment in cancer, in particular non-solid neoplasms.
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Page/Page column 32
(2009/10/22)
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- Synthesis of chiral 1,4-disubstituted-1,2,3-triazole derivatives from amino acids
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A versatile method for the synthesis of chiral 1,4-disubstituted-1,2,3- triazole derivatives starting from easily accessible naturally occurring D-or L-amino acids as chiral synthons is described. The amino acids were converted into azido alcohols, followed by copper catalyzed [3+2] cycloaddition reactions between the azido alcohols and methyl propiolate and subsequent ester aminolysis with primary and secondary amines furnished the target compounds, which were obtained in excellent yields with no racemization. Docking of selected target compounds shows that the chiral 1,4-disubstituted-1,2,3-triazoles derivatives has the potential of mimicking the binding mode of known purine analogues.
- Klein, Michael,Krainz, Karin,Redwan, Itedale Namro,Diner, Peter,Grotli, Morten
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experimental part
p. 5124 - 5143
(2010/03/25)
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- SUBSTITUTED CHIRAL FUSED [1,2]IMIDAZO[4,5-C] RING COMPOUNDS
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Substituted fused [1,2]imidazo[4,5-c] ring compounds (e.g., imidazo[4,5-c]quinolines, 6,7,8,9-tetrahydroimidazo[4,5-c]quinolines, imidazo[4,5-c]naphthyridines, and 6,7,8,9-tetrahydroimidazo[4,5-c]naphthyridines) with a -CH(-R1)- group in the fused ring at the 1-position of the imidazo ring, wherein Rl includes a functional group, for example, an amide, sulfonamide, urea, carbamate, ester, ketone, ether, a thio analog of the forgoing, sulfone, oxime, or hydroxylamine, pharmaceutical compositions containing the compounds, intermediates, methods of making the compounds, and methods of use of these compounds as immunomodulators, for inducing cytokine biosynthesis in animals and in the treatment of diseases including viral and neoplastic diseases, are disclosed.
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Page/Page column 142
(2008/06/13)
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- HYDROXYMORPHOLINONE DERIVATIVE AND MEDICINAL USE THEREOF
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A compound represented by the following formula (I) wherein R1 and R2 are each a lower alkyl group optionally having substituents, which has a calpain inhibitory activity, or a salt thereof is provided.
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- Rearrangements and racemisation during the synthesis of L-serine derived oxazolidin-2-ones
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The propensity for N-Boc-4-hydroxymethyl-oxazolidin-2-ones to undergo rapid O-O and N-O carbonyl transfer makes these L-serine derived chiral auxiliaries unsuitable for attachment to polymers.
- Bew, Sean P,Bull, Steven D,Davies, Stephen G,Savory, Edward D,Watkin, David J
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p. 9387 - 9401
(2007/10/03)
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- Chelated complexes of paramagnetic metals with low toxicity
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Compounds of formulae (I) and (II) wherein the R, R1, R2, R3 and R4 groups have the meanings defined in the disclosure, are useful chelants for metal ions. The complexes of compounds (I) and (II) with paramagnetic ions are useful as contrast agents for M.R.I. imaging.
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- Synthesis and biological evaluation of a new class of vaccine adjuvants: Aminoalkyl glucosaminide 4-phosphates (AGPs)
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A novel series of acylated ω-aminoalkyl 2-amino-2-deoxy-4-phosphono-β- D-glucopyranosides (aminoalkyl glucosaminide 4-phosphates) was synthesized and screened for immunostimulant activity. Several of these compounds enhance the production of tetanus toxoid-specific antibodies in mice and augment vaccine-induced cytotoxic T cells against EG.7-ova target cells.
- Johnson, David A.,Sowell, C. Gregory,Johnson, Craig L.,Livesay, Mark T.,Keegan, David S.,Rhodes, Michael J.,Ulrich, J. Terry,Ward, Jon R.,Cantrell, John L.,Brookshire, Valerie G.
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p. 2273 - 2278
(2007/10/03)
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- Chelated complexes of paramagnetic metals with low toxicity
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Compounds of formulae (I) and (II) wherein the R, R1, R2, R3and R4groups have the meanings defined in the disclosure, are useful chelants for metal ions. The complexes of compounds (I) and (II) with paramagnetic ions are useful as contrast agents for M.R.I. imaging.
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- Synthesis of the (α,α-difluoroalkyl)phosphonate analogue of phosphoserine
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The synthesis of the (α,α-difluoroalkyl)phosphonate analogue of L- phosphoserine, 5, in a form appropriate for solid phase peptide synthesis, is reported. Two independent routes are described, starting from L-serine or (R)-isopropylideneglycerol. In each case, PCF2-C bond formation is achieved by triflate displacement with diethyl lithiodifluoromethylphosphonate.
- Berkowitz, David B.,Shen, Quanrong,Maeng, Jun-Ho
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p. 6445 - 6448
(2007/10/02)
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- Aldehyde derivatives and their use as calpain inhibitors
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Aldehyde derivatives with a specific calpain inhibiting activity and a platelet-aggregation inhibiting effect with formula (I) or formula (II): wherein R1 represents an aromatic hydrocarbon group, a heterocyclic group, or a group of-X-R3 in which X represents O,-S(O)m-(m = 0, 1, or 2), and R3 represents an aromatic hydrocarbon group, a heterocyclic group, or an alkyl group; Z represents R?-Y-or R?O-CH(R?)-in which Y represents a 3-to 7-membered nitrogen-containing saturated heterocyclic group, or a single cyclic saturated hydrocarbon group, R? represents an alkyl group, an alkenyl group, an alkynyl group, an acyl group, a sulfonyl group, an alkoxycarbonyl group, a carbamoyl group, or a thiocarbamoyl group, R? represents hydrogen, an alkyl group, or an aromatic hydrocarbon group, and R? represents an acyl group, a carbamoyl group, a thiocarbamoyl group, or an alkyl group; and n is an integer of 1 to 5. wherein R?, R?, R?, and R1? are defined in the specification.
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- Synthesis of Diastereomerically Pure 2,5-Disubstituted 3-Oxoperhydro-1,4-oxazines
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The syntheses of hitherto unknown, diastereomerically pure 2,5-disubstituted 3-oxoperhydro-1,4-oxazines ("3-morpholinones") are described.The conventional preparation of 3-morpholinones by direct condensation of sodium aminoalcoholates with esters of α-halogenocarboxylic acids is complemented by an alternative and milder two-step synthetic strategy.The methyl and hydroxyalkyl derivatives are characterized by their NMR-spectroscopical and optical data.
- Danklmaier, Johann,Hoenig, Helmut
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p. 851 - 854
(2007/10/02)
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