Efficient synthetic routes in fluorinated isosteres of inositol and their effects on cellular growth

Kozikowski, Alan P.; Fauq, Abdul H.; Powis, Garth; Melder, Deborah C.

doi:10.1021/ja00167a061

Cited by 85 publications

(23 citation statements)

References 1 publication

(4 reference statements)

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“…2-dimethyl-3,4,5,7-tetrahydro-1,3- 3,2.3,10.4,11.5,Hz,1 H),5.80 (ddddd,J = 1.5,1.5,1.6,3.2,10.4 Hz,1 H),5.25 (dddddd,J = 1.6,2.0,2.3,5.6,9.1,49.4 Hz, 1 H), 4.51 (m, 2 H), 2.60 (ddddd, J = 1. 5,4.4,5.6,5.6,13.6 Hz,1 H),1.91 (dddd,J = 2.9,9.1,13.6,14.8 Hz,1 H) 6.00 (dddd, J = 0. 5,2.5,9.8,10.2 Hz,1 H),5.03 (dddddd,J = 1.4,1.5,2.5,4.8,7.5,48.2 Hz,1 H),4.44 (dddd,J = 1.0,1.5,2.0,5.8 Hz,1 H),4.32 (ddd,J = 4.5,5.8,8.5 Hz,1 H),2.25 (dddd,J = 4.5,…”

Section: Experimental Section General Informationmentioning

confidence: 99%

“…These compounds fall within the category of carbohydrate mimics, which are frequently used as powerful molecular probes for studying the biological function of oligosaccharides present on cell membranes. [6] Results and Discussion Synthesis of fluorinated carbocycles: The synthesis of representative cyclic allylsilanes was carried out following a reaction sequence developed by Landais et al (Scheme 2, TMEDA = tetramethylethylenediamine).…”

Section: Introductionmentioning

confidence: 99%

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Sequential Desymmetrization–Fluorination: Enantioselective Synthesis of Fluorinated Cyclitols

Purser

Odell

Claridge

et al. 2006

Chemistry A European J

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An asymmetric synthesis of enantioenriched, highly functionalized fluorinated carbocycles has been developed based on an enantioselective Sharpless dihydroxylation of cyclohexadienylsilanes, combined with a diastereoselective electrophilic fluorodesilylation. Several parameters define the level of diastereocontrol for the fluorination step. These include the relative stereochemistry of the starting endocyclic allylsilanes and the structural features of the reactants. As expected for an S(E)2' mechanism, the fluorodesilylation occurred with clean transposition of the double bond, with the attack of the electrophilic fluorinating agent taking place preferentially anti to the silyl group. For the fluorination step, the best selectivities were observed for the monocyclic anti,syn benzyl-protected precursors and for the syn,syn starting allylsilane. Full NMR spectroscopic analysis of the fluorinated monocyclic compounds, which possess an endocyclic double bond flanked by two electronegative groups (the methoxy group and the fluorine substituent) revealed that a subtle combination of steric (1,3-axial/pseudoaxial interaction) and stereoelectronic effects (pi-sigma* interaction) favours the preferential conformers featuring the methoxy group in a pseudoaxial position.

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Section: Experimental Section General Informationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sequential Desymmetrization–Fluorination: Enantioselective Synthesis of Fluorinated Cyclitols

Purser

Odell

Claridge

et al. 2006

Chemistry A European J

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“…phase was concentrated under reduced pressure to afford 1 (12.60 g, 89%). White crystalline solid [11] …”

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confidence: 99%

Synthesis of 4/5‐Deoxy‐4/5‐nucleobase Derivatives of 3‐O‐Methyl‐D‐chiro‐inositol as Potential Antiviral Agents

Zhan¹,

Ma²,

Fan³

et al. 2006

Chemistry & Biodiversity

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Using D-pinitol (= 3-O-methyl-D-chiro-inositol) as starting material, a concise synthesis of 4/5-deoxy-4/5-nucleobase derivatives 11-19 has been achieved. The key intermediate 9 was obtained in good yield via an epoxidation from mono-methanesulfonate of D-pinitol. The process of opening of the epoxide ring in 9 by nucleobases appeared to be regioselective in presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). All the synthesized carbocyclic nucleosides were assayed against several viruses and tumors such as HIV-1, HSV-1, and HSV-2, and lung and bladder cancer. However, only compounds 14b, 14a, 16a, 16b, and 19 showed mild inhibitory effect against human lung cancer cell lines (PG) with IC50 values ranging from 50 to 100 microM, and the other compounds did not exhibit any significant antiviral activity or cytotoxicity even at concentrations up to 200 microM.

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“…The inclusion of fluorine in enzyme substrates has been recognised as a useful technique for the generation of enzyme inhibitors. Fluorinated analogues of myo-inositol were used as potential inhibitors of the phosphoinositide metabolism in different cells (Moyer et al 1988, Kozikowski et al 1990, McPhee et al 1991, Cosulich et al 1993. The rationale was that these monodeoxyfluoro-myo-inositols (nFIns) might be taken up into cells by the same uptake process as myo-inositol, and either be incorporated into phosphoinositides or prevent their formation, depending on the position of the fluorine substituent.…”

Section: Fluorinated Inositol Analoguesmentioning

confidence: 99%

Inositol metabolism in Trypanosoma cruzi: potential target for chemotherapy against Chagas' disease

Oliveira

Einicker‐Lamas

2000

An. Acad. Bras. Ciênc.

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Chagas' disease is a debilitating and often fatal disease caused by the protozoan parasite Trypanosoma cruzi. The great majority of surface molecules in trypanosomes are either inositol-containing phospholipids or glycoproteins that are anchored into the plasma membrane by glycosylphosphatidylinositol anchors. The polyalcohol myo-inositol is the precursor for the biosynthesis of these molecules. In this brief review, recent findings on some aspects of the molecular and cellular fate of inositol in T. cruzi life cycle are discussed and identified some points that could be targets for the development of parasite-specific therapeutic agents.

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Efficient synthetic routes in fluorinated isosteres of inositol and their effects on cellular growth

Cited by 85 publications

References 1 publication

Sequential Desymmetrization–Fluorination: Enantioselective Synthesis of Fluorinated Cyclitols

Sequential Desymmetrization–Fluorination: Enantioselective Synthesis of Fluorinated Cyclitols

Synthesis of 4/5‐Deoxy‐4/5‐nucleobase Derivatives of 3‐O‐Methyl‐D‐chiro‐inositol as Potential Antiviral Agents

Inositol metabolism in Trypanosoma cruzi: potential target for chemotherapy against Chagas' disease

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