73746-79-9Relevant academic research and scientific papers
LYMPH DIRECTING PRODRUGS
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Page/Page column 75; 76, (2016/02/29)
H:\dar\Interwoven\NRPortbl\DCC\DAR\8230712_1.doc-12/08/2015 Abstract The present invention relates to compounds and their uses, in particular, compounds in the form of prodrugs that promote transport of a pharmaceutical agent to the lymphatic system and subsequently enhance release of the parent drug.
Enantioselective Construction of Quaternary Carbon Stereocenter via Palladium-Catalyzed Asymmetric Allylic Alkylation of Lactones
Li, Xiao-Hui,Wan, Shi-Li,Chen, Di,Liu, Qing Rong,Ding, Chang-Hua,Fang, Ping,Hou, Xue-Long
supporting information, p. 1568 - 1572 (2016/05/24)
An efficient and practical method for the synthesis of α,α-disubstituted six-membered lactones was developed. Enantioselective construction of quaternary carbon centers by utilizing Pd-catalyzed asymmetric allylic alkylation proved its feasibility.
Biocatalytic Characterization of Human FMO5: Unearthing Baeyer-Villiger Reactions in Humans
Fiorentini, Filippo,Geier, Martina,Binda, Claudia,Winkler, Margit,Faber, Kurt,Hall, Mélanie,Mattevi, Andrea
, p. 1039 - 1048 (2016/05/19)
Flavin-containing mono-oxygenases are known as potent drug-metabolizing enzymes, providing complementary functions to the well-investigated cytochrome P450 mono-oxygenases. While human FMO isoforms are typically involved in the oxidation of soft nucleophiles, the biocatalytic activity of human FMO5 (along its physiological role) has long remained unexplored. In this study, we demonstrate the atypical in vitro activity of human FMO5 as a Baeyer-Villiger mono-oxygenase on a broad range of substrates, revealing the first example to date of a human protein catalyzing such reactions. The isolated and purified protein was active on diverse carbonyl compounds, whereas soft nucleophiles were mostly non- or poorly reactive. The absence of the typical characteristic sequence motifs sets human FMO5 apart from all characterized Baeyer-Villiger mono-oxygenases so far. These findings open new perspectives in human oxidative metabolism.
Aldol Additions of Titanium and Boron Enolates of Achiral and Chiral δ-Lactones to Achiral Model Aldehydes: Simple and Induced Diastereoselectivities
Weber, Fabian,Becker, Fabian,Keller, Manfred,Hillebrecht, Harald,Brückner, Reinhard
supporting information, p. 7892 - 7918 (2015/12/24)
We studied the steric course of aldol additions of CpTiCl2 (novel) or Bu2B enolates of the unsubstituted δ-lactone and of the four monomethylated δ-lactones to isobutyraldehyde, crotonaldehyde, and para-bromobenzaldehyde. The titanium enolates reacted syn-selectively with >95:5 ds in most cases. The boron enolates reacted anti-selectively without exception (ds = 98:2 to 92:8). These selectivities paired with a preferred trans-orientation of the α-hydroxyalkyl substituents relative to the lactone's β- or γ-methyl group and with a preferred cis-orientation relative to the lactone's δ-methyl group. Our preparation of γ-methyl-δ-lactone (20) features a tandem glycol cleavage/lactol → lactone conversion with cat. TEMPO/stoichiom. PhI(OAc)2, which we believe is novel. Aldol additions of CpTiCl2 and Bu2B enolates of δ-lactone and its monomethyl derivatives to model aldehydes were studied. The CpTiCl2 enolates reacted syn-selectively (ds >95:5), the Bu2B enolates anti-selectively (ds up to 98:2). The α-hydroxyalkyl groups were oriented trans relative to the lactone's β- or γ-methyl group but cis relative to the lactone's δ-methyl group.
Functional divergence between closely related Baeyer-Villiger monooxygenases from Aspergillus flavus
Ferroni,Smit,Opperman
, p. 47 - 54 (2014/07/07)
Baeyer-Villiger monooxygenases (BVMOs) catalyse the chemo-, regio- and enantioselective oxidation of ketones to esters and lactones. To date, most of the cloned BVMOs available are derived from bacteria, although Baeyer-Villiger oxidations using fungi have frequently been demonstrated. Here we report the cloning and characterization of four BVMOs from the fungus Aspergillus flavus NRRL3357. Phylogenetic analysis shows these four BVMOs to cluster in a distinct group apart from other well-characterized BVMOs including cyclohexanone, phenylacetone and 4-hydroxyacetophenone monooxygenase. Building on the Grogan classification/clustering of BVMOs, we have designated this new group of BVMOs, Group VI. Group VI BVMOs show an early divergence from the cyclopentanone monooxygenase (CPMO) type BVMOs (Group I). Substrate profiling using cyclic, bicyclic, aliphatic and aryl ketones show a clear divergence in function and specificity not only between this new group of BVMOs and the CPMO-type BVMOs, but also between the four A. flavus BVMO paralogues despite their high sequence similarity. This study not only contributes to the growing number of available BVMOs, but also addresses the current classification of Type I BVMOs, and the usefulness of phylogenetic clustering and prediction of function and selectivity when genome-mining is used to search for new biocatalysts.
Catalytic oxidation of cyclic ethers to lactones over various titanosilicates
Sasidharan, Manickam,Bhaumik, Asim
experimental part, p. 105 - 110 (2011/05/04)
Various crystalline microporous metallosilicates have been used in the liquid phase catalytic oxidation of different cyclic ethers into their corresponding lactones in the presence of dilute aqueous H2O 2 as oxidant. Among the various metallosilicates studied for the oxidation of tetrahydrofuran to γ-butyrolactone, titanosilicates exhibited the best activity than the other metallosilicates such as chromium silicalite-1 (CrS-1), chromium silicalite-2 (CrS-2) and vanadium silicalite-1 (VS-1). The intrinsic activity of TS-1 was found to be marginally higher than the other titanosilicates. Cyclic ethers undergo αC-H oxidation to give the corresponding lactones; whereas open-chain ether produce carboxylic acids by initial αC-H bond oxidation to give ester as an intermediate product, which further undergoes cleavage of -O- linkage to give the final carboxylic acids. The conversion of substituted tetrahydrofuran is decreased with number of -CH3 groups at α- and/or β-position. The lactone formation is hindered when both the α-positions are substituted with methyl substituents. Mechanistically, titanium hydroperoxo complex formed in the titanosilicate/H2O2/H2O system is believed to oxidize the αC-H bond of ethers producing the respective α-hydroxylated product, which undergoes further oxidation to give the lactones (for cyclic ethers) or carboxylic acids (for open-chain ethers).
Exploration of the interrupted Fischer indolization reaction
Schammel, Alex W.,Boal, Ben W.,Zu, Liansuo,Mesganaw, Tehetena,Garg, Neil K.
supporting information; experimental part, p. 4687 - 4695 (2010/08/06)
A convergent method to access the fused indoline ring system present in a multitude of bioactive molecules has been developed. The strategy involves the condensation of hydrazines with latent aldehydes to ultimately deliver indoline-containing products by way of an interrupted Fischer indolization sequence. The method is convergent, mild, operationally simple, broad in scope, and can be used to access enantioenriched products. In addition, our approach is amenable to the synthesis of furoindoline and pyrrolidinoindoline natural products as demonstrated by the concise formal total syntheses of physovenine and debromoflustramine B. The strategy will likely enable the synthesis of more complex targets such as the communesin alkaloids.
Remote control of regio- and diastereoselectivity in the hydroformylation of bishomoallylic alcohols with catalytic amounts of a reversibly bound directing group
Gruenanger, Christian U.,Breit, Bernhard
supporting information; experimental part, p. 967 - 970 (2010/05/02)
(Figure Presented) Remote and reversible! Phosphinites serve as reversibly bound directing groups for the remote control of the regio- and diastereoselective hydroformylation of bishomoallylic alcohols (see scheme; r.r: regioisomer ratio). The distance between the double bond and the functional hydroxy group to which the directing group is reversibly bound is the longest ever reported.
An interrupted fischer indolization approach toward fused indoline-containing natural products
Boal, Ben W.,Schammel, Alex W.,Garg, Neil K.
supporting information; experimental part, p. 3458 - 3461 (2009/12/07)
An efficient method to access the fused indoline ring system present in a multitude of bioactive molecules has been developed. The strategy involves the condensation of hydrazines with latent aldehydes to ultimately deliver indoline-containing products by way of an interrupted Fischer indolization sequence. Our studies show that the approach will likely be amenable to the synthesis of complex targets, such as the communesin natural products.
Synthesis and stereochemistry of the terminal spiroketal domain of the phosphatase inhibitor dinophysistoxin-2
Forsyth, Craig J.,Wang, Ce
, p. 3043 - 3046 (2008/12/23)
An expedient synthesis of both axially and equatorially C35 methyl substituted spiroketals representing the C28-C38 domain of the potent and selective protein serine/threonine phosphatase inhibitor dinophysistoxin-2 (DTX-2) was developed to enable comparative stereochemical analyses and a stereochemically correct total synthesis of DTX-2. Comparison of proton and carbon NMR data of the synthetic diastereomers with those published for DTX-2 indicates that DTX-2 possesses the (30S*,34R*,35S*)-relative configuration with an axial C35 methyl substituent.
