- Dramatic Effect of γ-Heteroatom Dienolate Substituents on Counterion Assisted Asymmetric Anionic Amino-Cope Reaction Cascades
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We report a dramatic effect on product outcomes of the lithium ion enabled amino-Cope-like anionic asymmetric cascade when different γ-dienolate heteroatom substituents are employed. For dienolates with azide, thiomethyl, and trifluoromethylthiol substituents, a Mannich/amino-Cope/cyclization cascade ensues to form chiral cyclohexenone products with two new stereocenters in an anti-relationship. For fluoride-substituted nucleophiles, a Mannich/amino-Cope cascade proceeds to afford chiral acyclic products with two new stereocenters in a syn-relationship. Bromide- and chloride-substituted nucleophiles appear to proceed via the same pathway as the fluoride albeit with the added twist of a 3-exo-trig cyclization to yield chiral cyclopropane products with three stereocenters. When this same class of nucleophiles is substituted with a γ-nitro group, the Mannich-initiated cascade is now diverted to a β-lactam product instead of the amino-Cope pathway. These anionic asymmetric cascades are solvent- and counterion-dependent, with a lithium counterion being essential in combination with etheral solvents such as MTBE and CPME. By altering the geometry of the imine double bond from E to Z, the configurations at the R1 and X stereocenters are flipped. Mechanistic, computational, substituent, and counterion studies suggest that these cascades proceed via a common Mannich-product intermediate, which then proceeds via either a chair (X = N3, SMe, or SCF3) or boat-like (X = F, Cl, or Br) transition state to afford amino-Cope-like products or β-lactam in the case of X = NO2.
- Das, Pradipta,Delost, Michael D.,Qureshi, Munaum H.,Bao, Jianhua,Fell, Jason S.,Houk, Kendall N.,Njardarson, Jon T.
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supporting information
p. 5793 - 5804
(2021/05/07)
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- INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND METHODS OF THEIR USE
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The present invention provides compounds of formula (I) wherein all of the variables are as defined herein. These compounds are inhibitors of indoleamine 2,3-dioxygenase (IDO), which may be used as medicaments for the treatment of proliferative disorders, such as cancer, viral infections and/or autoimmune diseases.
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Page/Page column 181
(2020/02/16)
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- IDO INHIBITORS
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There are disclosed compounds that modulate or inhibit the enzymatic activity of indoleamine 2,3-dioxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or inflammatory disorders utilizing the compounds of the invention.
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Paragraph 0578
(2016/10/27)
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- Discovery of AM-1638: A potent and orally bioavailable GPR40/FFA1 full agonist
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GPR40 (FFA1) is a G-protein-coupled receptor, primarily expressed in pancreatic islets, the activation of which elicits increased insulin secretion only in the presence of elevated glucose levels. A potent, orally bioavailable small molecule GPR40 agonist
- Brown, Sean P.,Dransfield, Paul J.,Vimolratana, Marc,Jiao, Xianyun,Zhu, Liusheng,Pattaropong, Vatee,Sun, Ying,Liu, Jinqian,Luo, Jian,Zhang, Jane,Wong, Simon,Zhuang, Run,Guo, Qi,Li, Frank,Medina, Julio C.,Swaminath, Gayathri,Lin, Daniel C.-H.,Houze, Jonathan B.
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supporting information
p. 726 - 730
(2012/10/30)
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- Manganese dioxide can oxidise unactivated alcohols under in situ oxidation-Wittig conditions
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The in situ alcohol oxidation-Wittig reaction using manganese dioxide as the oxidant has been applied to semi-activated and, for the first time, unactivated alcohols to furnish the corresponding α,β-unsaturated esters.
- Blackburn, Leonie,Wei, Xudong,Taylor, Richard J. K.
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p. 1337 - 1338
(2007/10/03)
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- Baccatin derivatives and processes for preparing the same
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A compound represented by the formula [I]: STR1 wherein R3 represents a lower alkanoyl group; R4 represents a substituted or unsubstituted benzoyl group; ring A represents a substituted or unsubstituted cyclopropane ring; X represent
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- MIRC (Michael Initiated Ring Closure) Reactions Formation of Three, Five, Six and Seven Membered Rings
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The term MIRC reaction is defined. Examples of the construction of three, five, six and seven membered rings using alkylthiolates and LDA as nucleophiles are presented.
- Little, R.Daniel,Dawson, James R.
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p. 2609 - 2612
(2007/10/02)
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