Fluorous Mixture Synthesis Research Articles

Concise Synthesis of All Stereoisomers of Dendroamide A by Fluorous Mixture Synthesis Based on Fluorous‐Fmoc Protection of Amino Acids

AbstractA liquid‐phase split‐type synthesis of all the stereoisomers of dendroamide A, which exhibits multidrug‐resistance reversing activity, has been carried out. The key to the concise synthesis was the fluorous‐Fmoc protection strategy of each of the starting materials (D‐ and L‐alanine and D‐ and L‐valine). By using the fluorous‐Fmoc encoding method, the target stereoisomers were effectively synthesized individually in fewer steps than by the corresponding linear synthetic routes.

Fluorous mixture synthesis of fluorous-Fmoc reagents using a one-pot double tagging strategy

The concise synthesis of fluorous Fmoc (f-Fmoc) reagents bearing C3F7 or C4F9 or C6F13 chains were achieved by fluorous mixture synthesis. The fluorous tagging process was effectively conducted using Heck type reaction of the bis-diazonium salt and the corresponding fluorous olefine, each bearing a different fluorous tag, by a one-pot double tagging strategy. At the final stage, each f-Fmoc reagent was separated from the mixture of three f-Fmoc reagents by fluorous solid phase extraction.

Bare-Minimum Fluorous Mixture Synthesis of a Stereoisomer Library of 4,8,12-Trimethylnonadecanols and Predictions of NMR Spectra of Saturated Oligoisoprenoid Stereoisomers

All four diastereomers of a typical saturated oligoisoprenoid, 4,8,12-trimethylnonadecanol, are made by an iterative three-step cycle with the aid of traceless thionocarbonate fluorous tags to encode configurations. The tags have a minimum number of total fluorine atoms, starting at zero and increasing in increments of one. With suitable acquisition and data processing, each diastereomer exhibits characteristic chemical shifts of methyl resonances in its (1)H and (13)C NMR spectra. Together, these shifts provide a basis to predict the appearance of the methyl region of the spectrum of every stereoisomer of higher saturated oligoisoprenoids.

Binary fluorous tagging enables the synthesis and separation of a 16-stereoisomer library of macrosphelides

Fluorous mixture synthesis minimizes the effort to synthesize small molecule libraries by labeling the molecules rather than the reaction vessels. Reactants are labeled with fluorinated tags and products can later be demixed based on fluorine content. A limit in the number of available tags can be overcome by using binary encoding so that a total of four tags can be used to uniquely label a library of sixteen compounds. This strategy, however, means that separation based on fluorine content alone is no longer possible. Here, we solve this problem by selectively removing one tag after an initial demixing step; a second demixing provides each individual compound. The usefulness of this strategy is demonstrated by synthesizing a library containing all sixteen diastereomers of the natural products macrosphelides A and E. Macrosphelide D was not in this library, and so its assigned structure is incorrect. We determined its constitution by using NMR spectroscopy and its configuration by synthesizing four candidate stereoisomers.

Synthesis and Spectroscopic Analysis of a Stereoisomer Library of the Phytophthora Mating Hormone α1 and Derived Bis-Mosher Esters

Fluorous mixture synthesis provided all eight diastereomers of the phytophthora hormone α1 with the R configuration at C11 as individual samples after demixing and detagging. The library of all possible bis-Mosher esters (16) was then made by esterification. Complete sets of (1)H, (13)C, and (for the Mosher esters) (19)F NMR spectra were recorded, assigned, and compared with each other and with published spectra. Not all of the spectra are unique, and the (1)H NMR spectra of the Mosher esters provided the most information. The previous assignment of the natural sample as an "all-R" stereoisomer mixed with its 3S-epimer was confirmed.

Total synthesis of cucurbitoside-like phenolic glycosides by double fluorous and acyl mixture synthesis

The first and simultaneous total syntheses of cucurbitosides A, B, G, and I, seguinosides C and D, and two unnatural analogs were achieved using the technique of fluorous mixture synthesis. The eight precursors of cucurbitoside-like phenolic glycosides were prepared by glycosylation of a mixture of two glucopyranosyl acceptors bearing different fluorous benzyl groups with a mixture of four apiofuranosyl donors bearing benzoyl, 3-methylbutyryl, 4-benzyloxybenzoyl, and 4-nitrobenzoyl groups, followed by a single run of HPLC with serially connected Fluophase ® RP and Inertsil ® ODS-3 columns. Finally, the individual pure disaccharide precursors were detagged to yield the eight cucurbitoside-like phenolic glycosides.

Fluorous Mixture Synthesis of Four Stereoisomers of the C21-C40 Fragment of Tetrafibricin

Fluorous Mixture Synthesis of Four Stereoisomers of the C21-C40 Fragment of Tetrafibricin

ChemInform Abstract: Fluorous Mixture Synthesis (FMS) of Drug‐Like Molecules and Enantiomers, Stereoisomers, and Analogues of Natural Products

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Assignment of the structure of petrocortyne A by mixture syntheses of four candidate stereoisomers.

Two different mixture synthesis routes have been used to make the four stereoisomers of petrocortyne A. A first quick and dirty route provided a mixture of the four isomers in nonselective fashion. Mosher and 2-naphthylmethoxyacetic acid (NMA) ester methods were developed to identify the components, and the mixture was partially resolved on analytical chiral HPLC to give the two pure enantiomers of petrocortyne A and the racemate of its diastereomer. A second fluorous mixture synthesis produced all four isomers of petrocortyne A in individual pure form. Comparison of spectra of Mosher derivatives of the synthetic isomers with two supposedly different natural products showed that both natural samples were instead identical and had the (3S,14S) configuration. Likewise, petrocortynes B, D, and F-H are (3S,14S) and petrocortyne D is (3R,14S). Having access to all possible candidate isomers of both petrocortyne A and its Mosher derivatives provided a secure structure assignment not so much because one of the isomers matched the natural product, but because all of the other isomers did not.

Fluorous Mixture Synthesis of Asymmetric Dendrimers

A divergent fluorous mixture synthesis (FMS) of asymmetric fluorinated dendrimers has been developed. Four generations of fluorinated dendrimers with the same fluorinated moiety were prepared with high efficiency, yield, and purity. Comparison of the physicochemical properties of these dendrimers provided valuable information for their application and future optimization. This strategy has not only provided a practical method for the synthesis and purification of dendrimers, but also established the possibility of utilizing the same fluorinated moiety for FMS.

Fluorous Mixture Synthesis of Four Stereoisomers of the C21-C40 Fragment of Tetrafibricin

Fluorous Mixture Synthesis of Four Stereoisomers of the C21-C40 Fragment of Tetrafibricin

Fluorous Mixture Synthesis of Four Stereoisomers of the C21-C40 Fragment of Tetrafibricin.

Four stereoisomers of the C21-C40 fragment are synthesized in a single exercise with the aid of fluorous tagging to encode configurations at C37 and C33. After demixing and detagging, the isomers were found to have substantially identical (1)H NMR spectra. However, there were some small but reliable differences in their (13)C NMR spectra.

Cover Picture: Divergent Syntheses of Resorcylic Acid Lactones: L-783277, LL-Z1640-2, and Hypothemycin / Synthesis of a Resorcylic Acid Lactone (RAL) Library Using Fluorous-Mixture Synthesis and Profile of its Selectivity Against a Panel of Kinases (Chem.

The different faces of chemical biology, synthesis, compound libraries, functional annotation. On the front face of the cube, the synthesis of a resorcyclic acid library is represented as a circuit combining the different library components along the synthetic pathway based on fluorous isolation technology. The top face represents the functional annotation of the library members in the kinome. For details on the synthesis and activities of this library, see the articles by N. Winssinger et al. on pages 11490 ff. and 11498 ff.

Synthesis of a Resorcylic Acid Lactone (RAL) Library Using Fluorous‐Mixture Synthesis and Profile of its Selectivity Against a Panel of Kinases

A library of resorcylic acid lactones (RAL) containing a cis-enone moiety targeting kinases bearing a cysteine residue within the ATP-binding pocket was prepared using a fluorous-mixture synthesis and evaluated against a panel of 19 kinases thus providing important structure-activity trends. Two new analogues were then profiled for their selectivity against a panel of 402 kinases providing the broadest evaluation of this pharmacophores' selectivity.

Total synthesis of macrocyclic glycosides, clemochinenosides A and B, and berchemolide, by fluorous mixture synthesis

The total synthesis of clemochinenoside A and the first total syntheses of clemochinenoside B and berchemolide were achieved simultaneously via macrocyclization of 4- O-(4- O- F13benzyl-β- d-glucopyranosyl)syringic acid with 4- O-(4- O- F17benzyl-β- d-glucopyranosyl)vanillic acid by a fluorous mixture synthetic method. The spectroscopic data of the synthetic products were identical with those of the natural products, although the optical rotation of clemochinenoside A differed from the published values in sign and magnitude.

A “Shortcut” Mosher Ester Method To Assign Configurations of Stereocenters in Nearly Symmetric Environments. Fluorous Mixture Synthesis and Structure Assignment of Petrocortyne A

A "shortcut" of the advanced Mosher rule for use in assigning stereocenters in molecules with elements of local symmetry is proposed. A single Mosher ester is made, and the chemical shifts of pairs of resonances related by local symmetry are subtracted from each other (rather than from analogous resonances in the isomeric Mosher ester) to provide the configuration. Fluorous mixture synthesis is used to make a stereoisomer library of the four isomers of petrocortyne A. These samples and the derived Mosher esters are used to assign the (3S,14S) configuration to petrocortyne A and to validate both the standard and shortcut Mosher methods for use in the petrocortyne family of dialkynyl carbinols.

ChemInform Abstract: Confirmation of the Stereostructure of (+)‐Cytostatin by Fluorous Mixture Synthesis of Four Candidate Stereoisomers.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Confirmation of the Stereostructure of (+)-Cytostatin by Fluorous Mixture Synthesis of Four Candidate Stereoisomers

Confirmation of the Stereostructure of (+)-Cytostatin by Fluorous Mixture Synthesis of Four Candidate Stereoisomers

Confirmation of the Stereostructure of (+)‐Cytostatin by Fluorous Mixture Synthesis of Four Candidate Stereoisomers

Mix and match: Four closely related candidate isomers for cytostatin have been synthesized by using the technique of fluorous mixture synthesis. Comparison of NMR, thin-layer chromatography, and optical rotation data enabled the three isomers that were not cytostatin to be identified. Thus, by a process of elimination (disproof), the isomer corresponding to cytostatin was determined, and the 4S,5S,6S,9S,10S,11S configuration confirmed. (Chemical Equation Presented). © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.

Fluorous Mixture Synthesis による簡易ペプチド合成: フルオラス FMOC 試薬の合成とその反応

Fluorous Mixture Synthesis による簡易ペプチド合成: フルオラス FMOC 試薬の合成とその反応