- Strategic Approach to the Metamorphosis of γ-Lactones to NH γ-Lactams via Reductive Cleavage and C-H Amidation
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A new approach has elaborated on the conversion of γ-lactones to the corresponding NH γ-lactams that can serve as γ-lactone bioisosteres. This approach consists of reductive C-O cleavage and an Ir-catalyzed C-H amidation, offering a powerful synthetic tool for accessing a wide range of valuable NH γ-lactam building blocks starting from γ-lactones. The synthetic utility was further demonstrated by the late-stage transformation of complex bioactive molecules and the asymmetric transformation.
- Jung, Hoi-Yun,Chang, Sukbok,Hong, Sungwoo
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supporting information
p. 7099 - 7103
(2019/09/07)
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- Cooperative iodine and photoredox catalysis for direct oxidative lactonization of carboxylic acids
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A new method for the formation of γ- and δ-lactones from carboxylic acids through direct conversion of benzylic C-H to C-O bonds is described. The reaction is conveniently induced by visible light and relies on a mild cooperative catalysis by the combination of molecular iodine and an organic dye.
- Duhamel, Thomas,Mu?iz, Kilian
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supporting information
p. 933 - 936
(2019/01/23)
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- Synthesis of the pentacylic core of (+)-salvileucalin B
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A concise preparation of the prochiral pentacyclic core of (+)-salvileucalin B is presented. The key feature in the synthesis is the Cu-catalyzed intramolecular cyclopropanation of a symmetrical indane-derived α-diazo β-keto ester. This symmetry is carrie
- Taber, Douglass F.,Paquette, Craig M.
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p. 3410 - 3413
(2014/05/06)
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- Tricyclic [1,2,4]triazine 1,4-dioxides as hypoxia selective cytotoxins
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A series of novel tricyclic triazine-di-N-oxides (TTOs) related to tirapazamine have been designed and prepared. A wide range of structural arrangements with cycloalkyl, oxygen-, and nitrogen-containing saturated rings fused to the triazine core, coupled with various side chains linked to either hemisphere, resulted in TTO analogues that displayed hypoxia-selective cytotoxicity in vitro. Optimal rates of hypoxic metabolism and tissue diffusion coefficients were achieved with fused cycloalkyl rings in combination with both the 3-aminoalkyl or 3-alkyl substituents linked to weakly basic soluble amines. The selection was further refined using pharmacokinetic/pharmacodynamic model predictions of the in vivo hypoxic potency (AUCreq) and selectivity (HCD) with 12 TTO analogues predicted to be active in vivo, subject to the achievement of adequate plasma pharmacokinetics.
- Hay, Michael P.,Hicks, Kevin O.,Pchalek, Karin,Lee, Ho H.,Blaser, Adrian,Pruijn, Frederik B.,Anderson, Robert F.,Shinde, Sujata S.,Wilson, William R.,Denny, William A.
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supporting information; experimental part
p. 6853 - 6865
(2009/12/03)
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- TRICYCLIC 1,2,4-TRIAZINE OXIDES AND COMPOSITIONS THEREFROM FOR THERAPEUTIC USE IN CANCER TREATMENTS
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The invention relates to novel tricyclic 1,2,4-triazine-1-oxides and novel tricyclic 1,2,4-triazine-1,4-dioxides of formula: (I); and to related analogues, to their preparation, and to their use as hypoxia-selective drugs and radiosensitizers for cancer therapy, both alone or in combination with radiation and/or other anticancer drugs.
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Page/Page column 120
(2008/06/13)
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- New potent prolyl endopeptidase inhibitors: Synthesis and structure- activity relationships of indan and tetralin derivatives and their analogues
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New compounds were synthesized by structural modification of 1-[1-(4- phenylbutanoyl)-L-prolyl]-pyrrolidine (SUAM-1221, 1) or 1-[1- (benzyloxycarbonyl)-L-prolyl]prolinal (Z-Pro-prolinal, 2) and were tested for in vitro inhibitory activities against purified prolyl endopeptidase (PEP) from canine brain. In a series of compounds which lack a formyl or a cyano group, 3-[3-[(S)-2-(1,2,3,4-tetrahydronaphthyl)acetyl]-L- thioprolyl]thiazolidine (13) exhibited an approximately 20-fold (IC50 = 2.3 nM) increase in potency compared with 1. Compounds having a formyl or a cyano group showed much more potent inhibitory activities than those which lack such a functional group. Among all compounds tested in vitro, 1-[1-(2- indanylacetyl)-L-prolyl]prolinal (27), 1-[1-[(S)-2-(1,2,3,4- tetrahydronaphthyl)acetyl]-L-prolyl]prolinal (29), 1-[3-[(S)-2-(1,2,3,4- tetrahydronaphthyl)-acetyl]-L-thioprolyl]prolinal (30), (S)-2-cyano-1-[2- [(S)-2-(1,2,3,4-tetrahydronaphthyl)acetyl]-L-prolyl]pyrrolidine (34), and (S)-2-cyano-1-[3-[(S)-2-(1,2,3,4-tetrahydronaphthyl)acetyl]-L- thioprolyl]pyrrolidine (35) showed an approximately 2-fold (IC50 ? 0.5 nM) increase in potency compared with 2. The structure-activity relationships of these compounds are discussed.
- Tanaka,Niwa,Nishioka,Yamanaka,Torizuka,Yoshinaga,Kobayashi,Ikeda,Arai
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p. 2071 - 2078
(2007/10/02)
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