Search results for " Synthesis"
showing 10 items of 1625 documents
Conformationally Locked Pyramidality Explains the Diastereoselectivity in the Methylation of trans-Fused Butyrolactones
2020
A stereoselectivity model inspired by the total synthesis of stemona alkaloids is developed to explain why enolate-derived 3,4-fused butyrolactones are methylated with a preference for syn alkylation. The model shows how conformational locking present in nonplanar enolate structures favors syn over anti methylation, due to less significant structural distortions in the syn pathway. The developed model was also successfully used to rationalize selectivities of previously documented methylation reactions. peerReviewed
Rethinking Cysteine Protective Groups:S-Alkylsulfonyl-l-Cysteines for Chemoselective Disulfide Formation
2016
The ability to reversibly cross-link proteins and peptides grants the amino acid cysteine its unique role in nature as well as in peptide chemistry. We report a novel class of S-alkylsulfonyl-l-cysteines and N-carboxy anhydrides (NCA) thereof for peptide synthesis. The S-alkylsulfonyl group is stable against amines and thus enables its use under Fmoc chemistry conditions and the controlled polymerization of the corresponding NCAs yielding well-defined homo- as well as block co-polymers. Yet, thiols react immediately with the S-alkylsulfonyl group forming asymmetric disulfides. Therefore, we introduce the first reactive cysteine derivative for efficient and chemoselective disulfide formation…
tBuLi-Mediated One-Pot Direct Highly Selective Cross-Coupling of Two Distinct Aryl Bromides.
2015
A Pd-catalyzed direct cross-coupling of two distinct aryl bromides mediated by tBuLi is described. The use of [Pd-PEPPSI-IPr] or [Pd-PEPPSI-IPent] as catalyst allows for the efficient one-pot synthesis of unsymmetrical biaryls at room temperature. The key for this selective cross-coupling is the use of an ortho-substituted bromide that undergoes lithium-halogen exchange preferentially.
Synthesis and biological evaluation of 2- and 3-aminobenzo[b]thiophene derivatives as antimitotic agents and inhibitors of tubulin polymerization.
2007
Two new series of inhibitors of tubulin polymerization based on the 2-amino-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene molecular skeleton and its 3-amino positional isomer were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. Although many more 3-amino derivatives have been synthesized so far, the most promising compound in this series was 2-amino-6-methyl-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene, which inhibits cancer cell growth at subnanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site.
Semisynthesis of antitumoral acetogenins: SAR of functionalized alkyl-chain bis-tetrahydrofuranic acetogenins, specific inhibitors of mitochondrial c…
2000
The acetogenins of Annonaceae are known by their potent cytotoxic activity. In fact, they are promising candidates as a new future generation of antitumoral drugs to fight against the current chemiotherapic resistant tumors. The main target enzyme of these compounds is complex I (NADH:ubiquinone oxidoreductase) of the mitochondrial respiratory chain, a key enzymatic complex of energy metabolism. In an attempt to characterize the relevant structural factor of the acetogenins that determines the inhibitory potency against this enzyme, we have prepared a series of bis-tetrahydrofuranic acetogenins with different functional groups along the alkyl chain. They comprise several oxo, hydroxylimino,…
Individual stereoisomers of phosphinic dipeptide inhibitor of leucine aminopeptidase
2008
Abstract Individual stereoisomers of the phosphinic pseudodipeptide hPheψ[P(O)(OH)CH2]Phe were obtained by stereoselective liquid chromatographic separation as N- and C-terminally protected derivative on quinidine carbamate modified silica stationary phase. The stereoisomeric purity, exceeding 95% for each fraction, was determined before and after deprotection using two independent methods. The absolute configuration was rationally assigned by application of enantiomerically pure phosphinic acid substrates in the synthetic procedure and correlation with biological activity of the products. Substantial differences in inhibition of leucine aminopeptidase by the individual isomers revealed nov…
Identification of a Terphenyl Derivative that Blocks the Cell Cycle in the G0−G1 Phase and Induces Differentiation in Leukemia Cells
2006
To further explore the SAR of resveratrol-related trans-stilbene derivatives, here we describe the synthesis of (a) a series of 3,5-dimethoxy analogues in which a variety of substituents were introduced at positions 2', 3', 4', and 5' of the stilbene scaffold and (b) a second group of derivatives (2-phenylnaphthalenes and terphenyls) that incorporate a phenyl ring as a bioisosteric replacement of the stilbene alkenyl bridge. We thoroughly characterized all of the new compounds with respect to their apoptosis-inducing activity and their effects on the cell cycle. One of the new derivatives, 13g, behaved differently from the others, as it was able to block the cell cycle in the G(0)-G(1) phas…
Enantioselective synthesis of herbertane sesquiterpenes: synthesis of (−)-α-formylherbertenol
2000
Abstract The synthesis of 4-hydroxy-3-[(1 S )-1,2,2-trimethylcyclopentyl]benzaldehyde [(−)-α-formylherbertenol 1 ], a herbertane-type sesquiterpene isolated from the leafy liverwort Herberta adunca , from β-cyclogeraniol is described. The synthesis is based on the previously described preparation of an enantiopure 1,2,2-trimethylcyclopentane synthon from which the characteristic aromatic moiety of 1 is elaborated, using a Robinson annulation and a palladium-catalysed methoxycarbonylation of an aryl triflate as key synthetic steps. The synthesis of the natural sesquiterpene (−)-α-herbertenol, also a natural sequiterpene, using the same methodology is also described.
One-Pot Synthesis of (.+-.)-Crispine A and Its C-Ring-Substituted Analogues.
2006
Synthesis of all 7αH-guaia-4,11-dien-3-one diastereomers from (+)-dihydrocarvone
2005
Abstract All four 7α H -guaia-4,11-dien-3-one diastereomers have been synthesized from the common intermediate 1α H ,10α-acetoxy-7α H -guaia-4,11-dien-3-one obtained from (+)-dihydrocarvone. The spectral features of the four diasteromers have been correlated and the structure and absolute configuration of 1β H ,10β H ,7α H -guaia-4,11-dien-3-one isolated from Pleocarphus revolutus has been confirmed.