Fluorine-containing organozinc reagents. V.

Greuter, Hans; Lang, R. W.; Romann, Andres J.

doi:10.1016/0040-4039(88)85143-8

Cited by 55 publications

(13 citation statements)

References 6 publications

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“…[20] [α]- D 23 +13.4 ( c 1.75, CHCl 3 )). Ester 7 was then exposed to Reformatskii-Claisen reaction [21,22] by treatment with TMSCl and activated Zn-dust in CH 3 CN at reflux for 24 h. Subsequent esterification of the crude acid product with a catalytic amount of concentrated H 2 SO 4 in ethanol at 50 °C furnished a 2:1 mixture (by 1 H-NMR analysis) of diastereomers 8 in 80% yield over 2-steps. This mixture could not be separated by silica gel column chromatography.…”

Section: Synthesis Of Ligands and Inhibitorsmentioning

confidence: 99%

Design of gem‐Difluoro‐bis‐Tetrahydrofuran as P2 Ligand for HIV‐1 Protease Inhibitors to Improve Brain Penetration: Synthesis, X‐ray Studies, and Biological Evaluation

et al. 2014

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Structure-based design, synthesis, biological evaluation and X-ray structural studies of fluorine containing HIV-1 protease inhibitors are described. The synthesis of both enantiomers of the gem-difluoro-bis-THF ligands was carried out in a stereoselective manner using a Reformatskii-Claisen reaction as the key step. Optically active ligands HIV-1LAI were converted to protease inhibitors. Two of these inhibitors (3 and 4) exhibited HIV-1 protease inhibitory Ki’s in picomolar range. Both inhibitors showed very potent antiviral activity with EC50 values of 0.8 nM and 3.1 nM respectively against the laboratory strain HIV-1LAI. Both inhibitors exhibited improved lipophilicity profiles compared to darunavir. Also, both inhibitors showed much improved blood-brain-barrier permeability in an in vitro model. A high resolution X-ray structure of inhibitor 4-bound HIV-1 protease was determined. The X-ray structure revealed that fluoro ligand makes extensive interactions with the HIV-1 protease S2 subsite, including hydrogen-bonding interactions with the protease backbone atoms. Also, both fluorine atoms on the bis-THF ligand formed strong interactions with the flap Gly48 carbonyl oxygen.

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Section: Synthesis Of Ligands and Inhibitorsmentioning

confidence: 99%

Design of gem‐Difluoro‐bis‐Tetrahydrofuran as P2 Ligand for HIV‐1 Protease Inhibitors to Improve Brain Penetration: Synthesis, X‐ray Studies, and Biological Evaluation

et al. 2014

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“…Most importantly, from the synthetic point of view, there were developed plenty of variants of this type of rearrangement. By way of example, the Carroll [6,7], the Johnson [8], the Eschenmoser [9,10] (including the Overman variant [11,12]), the Reformatsky [13,14], the ester enolate [15][16][17], and the Ireland-Claisen rearrangements [18][19][20] should be mentioned as some of the synthetically most useful variants regularly applied with non-fluorinated compounds.…”

Section: Introductionmentioning

confidence: 99%

Claisen rearrangements based on vinyl fluorides

Tranel¹,

Haufe²

2004

Journal of Fluorine Chemistry

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“…Alternative methods of synthesis of acylsilane compounds of this type could involve Gelb's methodology based upon tetrafluoroethene, or Lang's Reformatsky-Claisen rearrangement [26] of chlorodifluoroacetate esters (difficult to reproduce in our hands), or coupling of the Reformatsky reagent with an allylic halide [27] from ethyl bromodifluoroacetate (scaleable but based on an expensive starting material), followed by processing of the acid functionality to the acylsilane [28] (which is unknown chemistry for substrates of this type). On the laboratory scale, we believe that the directness of this methodology makes it attractive for the synthesis of this under exploited class of acylsilanes.…”

Section: Resultsmentioning

confidence: 99%