- One-Pot Deoxygenation and Substitution of Alcohols Mediated by Sulfuryl Fluoride
-
Sulfuryl fluoride is a valuable reagent for the one-pot activation and derivatization of aliphatic alcohols, but the highly reactive alkyl fluorosulfate intermediates limit both the types of reactions that can be accessed as well as the scope. Herein, we report the SO2F2-mediated alcohol substitution and deoxygenation method that relies on the conversion of fluorosulfates to alkyl halide intermediates. This strategy allows the expansion of SO2F2-mediated one-pot processes to include radical reactions, where the alkyl halides can also be exploited in the one-pot deoxygenation of primary alcohols under mild conditions (52-95% yield). This strategy can also enhance the scope of substitutions to nucleophiles that are previously incompatible with one-pot SO2F2-mediated alcohol activation and enables substitution of primary and secondary alcohols in 54-95% yield. Chiral secondary alcohols undergo a highly stereospecific (90-98% ee) double nucleophilic displacement with an overall retention of configuration.
- Epifanov, Maxim,Mo, Jia Yi,Dubois, Rudy,Yu, Hao,Sammis, Glenn M.
-
p. 3768 - 3777
(2021/03/01)
-
- Metal-free hydrogenation of electron-poor allenes and alkenes
-
The poorer, the better: A metal-free catalytic procedure for the reduction of electron-poor allenes and alkenes has been developed. The method employs a frustrated Lewis pair based catalyst. 1,4-Diazabicyclo[2.2.2]octane (DABCO)/B(C6F5)3 was shown to be the best combination in optimization studies. Copyright
- Ines, Blanca,Palomas, David,Holle, Sigrid,Steinberg, Sebastian,Nicasio, Juan A.,Alcarazo, Manuel
-
supporting information
p. 12367 - 12369
(2013/02/22)
-
- Lipase-mediated preparation of optically active isomers of Rosaphen
-
The optically active isomers of Rosaphen (RS)-1 were synthesized from the chiral intermediate prepared by lipase-catalyzed desymmetrization of prochiral diol. The results of an olfactory evaluation of the prepared isomers are reported.
- Kawasaki, Masashi,Toyooka, Naoki,Saka, Tomoki,Goto, Michimasa,Matsuya, Yuji,Kometani, Tadashi
-
experimental part
p. 135 - 142
(2010/12/20)
-
- Impact of the carbon chain length of novel palladium(ll) Complexes on interaction with DNA and cytotoxic activity
-
A series of Pd(II) complexes with a benzenealkyl dicarboxlate chain, with the formulas [Pd(Ln)(bipy)].mH2O (bipy = 2,2'-bipyridine, complex 1: L1 = phenylmalonate, m = 2.5; complex 2: L2 = benzylmalonate, m = 1; complex 3: L3 = phenethylmatonate, m = 2; complex 4: L4 = phenylpropylmalonate, m = 5), have been prepared in an attempt to correlate factors about the carbon chain of the compounds with DNA binding and cytotoxic activity. The binding of complexes with fish sperm DNA (FS-DNA) was carried out by UV absorption and fluorescence spectra. A gel electrophoresis assay demonstrated the ability of the complexes to cleave the pBR322 plasmid DNA. The cytotoxic effects of these complexes were examined on four cancer cell lines, HeLa, Hep-G2, KB, and AGZY-83a. The four complexes exhibited cytotoxic specificity and a significant cancer cell inhibitory rate. An apparent dependence of DNAbinding properties and cytotoxicity on the carbon chain length was obtained: the longer the carbon chain length, the higher the efficiency of DNA-binding and the greater the cytotoxicity. 2010 American Chemical Society.
- Gao, Enjun,Zhu, Mingchang,Liu, Lei,Huang, Yun,Wang, Lei,Shi, Chuyue,Zhang, Wanzhong,Sun, Yaguang
-
experimental part
p. 3261 - 3270
(2010/06/13)
-
- Synthesis of the four stereoisomers of cyclobutane analogues of phenylalanine in enantiomerically pure form
-
All stereoisomers of 1-amino-2-phenylcyclobutanecarboxylic acid-c 4Phe-have been synthesized and the series cnPhe has thus been completed. The use of two different strategies based on a cyclization reaction, starting from ethyl isocy
- Lasa, Marta,Lopez, Pilar,Cativiela, Carlos
-
p. 4022 - 4033
(2007/10/03)
-
- Design, synthesis, and structure-activity relationships of haloenol lactones: Site-directed and isozyme-selective glutathione S-transferase inhibitors
-
Overexpression of glutathione S-transferase (GST), particularly the GST-π isozyme, has been proposed to be one of the biochemical mechanisms responsible for drug resistance in cancer chemotherapy, and inhibition of overexpressed GST has been suggested as an approach to combat GST-induced drug resistance. 3-Cinnamyl-5(E)-bromomethylidenetetrahydro-2-furanone (1a), a lead compound of site-directed GST-π inactivator, has been shown to potentiate the cytotoxic effect of cisplatin on tumor cells. As an initial step to develop more potent and more selective haloenol lactone inactivators of GST-π, we examined the relationship between the chemical structures of haloenol lactone derivatives and their GST inhibitory activity. A total of 16 haloenol lactone derivatives were synthesized to probe the effects of (1) halogen electronegativity, (2) electron density of aromatic rings, (3) molecular size and rigidity, (4) lipophilicity, and (5) aromaticity on the potency of GST-π inactivation. The inhibitory potency of each compound was determined by time-dependent inhibition tests, and recombinant human GST-π was used to determine their inhibitory activity. Our structure-activity relationship studies demonstrated that (1) reactivity of the halide leaving group plays a weak role in GST inactivation by the haloenol lactones, (2) aromatic electron density may have some influence on the potency of GST inactivation, (3) high rigidity likely disfavors enzyme inhibition, (4) lipophilicity is inversely proportional to enzyme inactivation, and (5) an unsaturated system may be important for enzyme inhibition. This work facilitated understanding of the interaction of GST-π with haloenol lactone derivatives as site-directed and isozyme-selective inactivators, possibly potentiating cancer chemotherapy.
- Wu, Zhixing,Minhas, Gurpreet Singh,Wen, Dingyi,Jiang, Hualiang,Chen, Kaixian,Zimniak, Piotr,Zheng, Jiang
-
p. 3282 - 3294
(2007/10/03)
-
- N-, α-, and β-substituted 3-aminopropionic acids: Design, syntheses and antiseizure activities
-
A treatment for epilepsy is proposed based on analogues of 3-aminopropionic acid (β-alanine), a putative neurotransmitter in the central nervous system (CNS). A model three point pharmacophore was proposed based on modelling data obtained from the study of antagonists for both the glial γ-aminobutyric acid (GABA)-uptake site and the glycine co-agonist site of N-methyl-D-aspartate (NMDA) receptor. Three series of 3-aminopropionic acids containing, N-, α-, and β-substituents, were designed and synthesized to probe the position and the size of a lipophilic binding pocket within the proposed pharmacophore. These analogues were tested in vivo for both their antiseizure activities and their neurologic toxicities. Among the fourteen novel 3-aminopropionic acids synthesized, eight were found to have promising antiseizure activity. This study shows that substitution on the N-terminus confers the greatest antiseizure activity, particularly against pilocarpine-induced seizures.
- Tan,Wainman,Weaver
-
p. 113 - 121
(2007/10/03)
-
- Design, synthesis, and structure-activity relationship of 6-alkynylpyrimidines as potent adenosine kinase inhibitors
-
Adenosine (ADO) is an extracellular signaling molecule within the central and peripheral nervous system. Its concentration is increased at sites of tissue injury and inflammation. One of the mechanisms by which antinociceptive and antiinflammatory effects of ADO can be enhanced consists of inhibition of adenosine kinase (AK), the primary metabolic enzyme for ADO. Novel nonnucleoside AK inhibitors based on 4-amino-6-alkynylpyrimidines were prepared, and the importance of the length of the linker at the 5-position for high affinity AK inhibition was demonstrated. Compounds with 2- and 3-atom linkers were the most potent AK inhibitors. Optimization of their physicochemical properties led to 31a and 37a that effectively reduced pain and inflammation in animal models.
- Gomtsyan, Arthur,Didomenico, Stanley,Lee, Chih-Hung,Matulenko, Mark A.,Kim, Ki,Kowaluk, Elizabeth A.,Wismer, Carol T.,Mikusa, Joe,Yu, Haixia,Kohlhaas, Kathy,Jarvis, Michael F.,Bhagwatt, Shripad S.
-
p. 3639 - 3648
(2007/10/03)
-
- SUBSTITUTE 4-ARYLBUTYRIC ACID DERIVATIVES AS MATRIX METALLOPROTEASE INHIBITORS
-
Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The compounds of the invention have generalized formula (I) wherein R represents C6-C12 alkyl; C5-C12 alkoxy; C5-C12 alkylthio; a polyether of formula RO(C2H4O)a- in which a is 1 or 2 and R is C1-C5 alkyl, phenyl, or benzyl; and substituted alkynyl of formula R(CH2)b-CC-; in which b is 1-10 and R is H-, HO-, or RO- in which R is C1-C3 alkyl, phenyl, or benzyl. The alkyl, phenyl, and benzyl portions of R may bear at least one pharmaceutically-acceptable substituent. The subscript n is 2-4. R represents phenyl; imidoyl of 4-12 carbon atoms; (3H)-benzo-1,2,3-triazin-4-on-3-yl; N-saccharinyl; (2H)-phthalazin-1-on-2-yl; 2-benzoxazolin-2-on-3-yl; 5,5-dimethyloxazolidine-2,4-dion-3-yl; and thiazolidine-2,4-dion-3-yl; with the phenyl and benzo portions of R permissibly bearing at least one pharmaceutically-acceptable substituent. Pharmaceutically acceptable salts of these materials are also included.
- -
-
-
- beta -thiopropionyl-aminoacid derivatives and their use as beta -lactamase inhibitors
-
PCT No. PCT/EP97/00516 Sec. 371 Date Jan. 13, 1999 Sec. 102(e) Date Jan. 13, 1999 PCT Filed Feb. 3, 1997 PCT Pub. No. WO97/30027 PCT Pub. Date Aug. 21, 1997A method of treatment of bacterial infections in humans or animals which comprises administering, in combination with a beta -lactam antibiotic, a therapeutically effective amount of an amino acid derivative of Formula (I) or a pharmaceutically acceptable salt, solvate or in vivo hydrolysable ester thereof, wherein: R is hydrogen, a salt forming cation or an in vivo hydrolysable ester-forming group; R1 is hydrogen, (C1-6)alkyl optionally substituted by up to three halogen atoms or by a mercapto, (C1-6)alkoxy, hydroxy, amino, nitro, carboxy, (C1-6)alkylcarbonyloxy, (C1-6)alkoxycarbonyl, formyl or (C1-6)alkylcarbonyl group, (C3-7)cycloalkyl, (C3-7)cycloalkyl(C2-6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, aryl, aryl(C1-6)alkyl, heterocyclyl or heterocyclyl(C1-6)alkyl; R2 is hydrogen, (C1-6)alkyl or aryl(C1-6)alkyl; R3 is hydrogen, (C1-6)alkyl optionally substituted by up to three halogen atoms, (C3-7)cycloalkyl, fused aryl(C3-7)cycloalkyl, (C3-7)cycloalkyl(C2-6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, aryl, aryl-(CHR10)m-X-(CHR11)n, heterocyclyl or heterocyclyl-(CHR10)m-X-(CHR11)n, where m is 0 to 3, n is 1 to 3, each R10 and R11 is independently hydrogen or (C1-4)alkyl and X is O, S(O)x where x is 0-2, or a bond; R4 is hydrogen, or an in vivo hydrolysable acyl group; and R5 and R6 are independently hydrogen and (C1-6)alkyl or together represent (CH2)p where p is 2 to 5. Some compounds are claimed per se.
- -
-
-
- SUBSTITUTED CYCLOALKANECARBOXYLIC ACID DERIVATIVES AS MATRIX METALLOPROTEASE INHIBITORS
-
Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The compounds of the invention have the generalized formula STR1 wherein each T is a substituent g roup; x is 0, 1, or 2; the group D represents STR2 the subscript "e" is 2 or 3; the group R 14 represents a variety of possible substituent groups of the cycloalkyl ring between D and G; the subscript "k" is 0-2; and the group G represents M, STR3 in which M represents--CO 2 H,--CON(R 11) 2, or--CO 2 R 12 ; and R 13 represents any of the side chains of the 19 noncyclic occurring amino acids. "
- -
-
-
- Phosphinic pseudo-tripeptides as potent inhibitors of matrix metalloproteinases: A structure-activity study
-
Several phosphinic pseudo-tripeptides of general formula R-XaaΨ(PO2- CH2)Xaa'-Yaa'-NH2 were synthesized and evaluated for their in vitro activities to inhibit stromelysin-3, gelatinases A and B, membrane type-1 matrix metalloproteinase, collagenases 1 and 2, and matrilysin. With the exception of collagenase-1 and matrilysin, phosphinic pseudo-tripeptides behave as highly potent inhibitors of matrix metalloproteinases, provided they contain in P1' position an unusual long aryl-alkyl substituent. Study of structure-activity relationships regarding the influence of the R and Xaa' substituents in this series may contribute to the design of inhibitors able to block only a few members of the matrix metalloproteinase family.
- Vassiliou, Stamatia,Mucha, Artur,Cuniasse, Philippe,Georgiadis, Dimitris,Lucet-Levannier, Karine,Beau, Fabrice,Kannan, Rama,Murphy, Gillian,Kn?uper, Vera,Rio, Marie-Christine,Basset, Paul,Yiotakis, Athanasios,Dive, Vincent
-
p. 2610 - 2620
(2007/10/03)
-