- Stereoselective Diboration of Spirocyclobutenes: A Platform for the Synthesis of Spirocycles with Orthogonal Exit Vectors
-
The diastereo- and enantioselective diboration of spirocyclobutenes provides a platform for the rapid preparation of a wide variety of chiral spirocyclic building blocks. The chemoselective functionalization of the carbon-boron bond in the products, including a stereospecific sp3-sp2 Suzuki–Miyaura cross-coupling reaction, provides a powerful tool to control the directionality and the nature of the exit vectors in the spirocyclic framework.
- Nóvoa, Luis,Trulli, Laura,Parra, Alejandro,Tortosa, Mariola
-
supporting information
p. 11763 - 11768
(2021/04/26)
-
- PYRAZOLE CARBOXAMIDE COMPOUNDS FOR TREATMENT OF HBV
-
The present disclosure provides, in part, pyrazole carboxamide compounds, and pharmaceutical compositions thereof, useful for disruption of HBV core protein assembly, and methods of treating Hepatitis B (HBV) infection.
- -
-
Page/Page column 58-59
(2021/10/30)
-
- PYRIDAZINONE DERIVATIVE
-
Provided are: a pyridazinone derivative and/or a pharmaceutically acceptable salt thereof, which is useful as a therapeutic agent and/or a prophylactic agent for diseases in which Nav1.1 is involved and various central nervous system diseases; and a medicine containing the pyridazinone derivative and/or the pharmaceutically acceptable salt thereof as an active ingredient. A compound represented by formula (1) or a pharmaceutically acceptable salt thereof. [In the formula, M1 represents a saturated or partially unsaturated C4-12 carbocyclic group or the like; R1 and R2 independently represent a hydrogen atom or the like; M2 represents a group represented by formula (2a) or the like; X1a, X1b and X1c independently represent N or the like; X2, X3 and X4 independently represent CR3 or the like; A1 and A2 independently represent N or the like; and R3 represents a hydrogen atom or the like.]
- -
-
Paragraph 0174
(2021/06/03)
-
- KINASE INHIBITORS
-
Disclosed herein are protein kinase inhibitors, in particular Bruton's tyrosine kinase (BTK) inhibitors, pharmaceutical compositions comprising them, processes for preparing them and uses of such protein kinase inhibitors to treat or prevent diseases, disorders and conditions associated with kinase function. In particular, the present invention relates to selective BTK inhibitors.
- -
-
Page/Page column 119; 120
(2021/10/15)
-
- N-(PYRIDIN-2-YLSULFONYL)CYCLOPROPANECARBOXAMIDE DERIVATIVES AND THEIR USE IN THE TREATMENT OF A CFTR MEDIATED DISEASE
-
The invention relates to heterocyclic compounds of the formula (I), in which all of the variables are as defined in the specification; capable of modulating the activity of CFTR. The invention further provides a method for manufacturing compounds of the invention, and its therapeutic uses. The invention further provides methods to their preparation, to their medical use, in particular to their use in the treatment and management of diseases or disorders including Cystic fibrosis and related disorders.
- -
-
Page/Page column 222
(2020/07/14)
-
- SPIRO COMPOUND AS INDOLEAMINE-2,3-DIOXYGENASE INHIBITOR
-
Disclosed in the present invention are an indoleamine-2,3-dioxygenase inhibitor and a preparation method therefor. The inhibitor of the present invention has a structure as represented by general formula (I), wherein the definitions of Ar, E, Y, X, V, D, W, B, ring A and ring B are as shown in the description and claims. Also disclosed in the present invention is a preparation method for the inhibitor. The compound of general formula (I) of the present invention can be used as an indoleamine-2,3-dioxygenase inhibitor for preparing a medicament for preventing and/or treating indoleamine-2,3-dioxygenase-mediated diseases.
- -
-
Paragraph 0228; 0229
(2020/12/29)
-
- Rhodium-Catalyzed Intermolecular Cyclopropanation of Benzofurans, Indoles, and Alkenes via Cyclopropene Ring Opening
-
The generation of metal carbenoids via ring opening of cyclopropenes by transition metals offers a simple entry into highly reactive intermediates. Herein, we describe a diastereoselective intermolecular rhodium-catalyzed cyclopropanation of heterocycles and alkenes using cyclopropenes as carbene precursors with a low loading of a commercially available rhodium catalyst. The reported method is scalable and could be performed with catalyst loadings as low as 0.2 mol %, with no impact to the reaction yield or selectivity.
- Jeyaseelan, Rubaishan,Lautens, Mark,Ross, Rachel J.
-
supporting information
(2020/06/29)
-
- STAT DEGRADERS AND USES THEREOF
-
The present invention provides compounds, compositions thereof, and methods of using the same.
- -
-
Paragraph 000981; 000982
(2020/10/19)
-
- MODULATORS OF INDOLEAMINE 2,3-DIOXYGENASE
-
Provided are IDO1 inhibitor compounds of Formula (I) and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and methods for their use in the prevention and/or treatment of diseases.
- -
-
Page/Page column 26
(2019/05/22)
-
- MACROCYCLIC MCL-1 INHIBITORS AND METHODS OF USE
-
The present disclosure provides for compounds of Formula (I) wherein A2, A3, A4, A6, A7, A8, A15, RA, R5, R9, R10A, R10B, R11, R12, R13, R14, R16, W, X, and Y have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including cancer. Also provided are pharmaceutical compositions comprising compounds of Formula (I).
- -
-
Paragraph 00727
(2019/03/05)
-
- MACROCYCLIC MCL-1 INHIBITORS AND METHODS OF USE
-
The present disclosure provides for compounds of formula (I), wherein A2, A3, A4, A6, A7, A8, A15, RA, R5, R9, R10A, R10B, R11, R12, R13, R14, R16, W, X, and Y have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including cancer. Also provided are pharmaceutical compositions comprising compounds of formula (I).
- -
-
Paragraph 00408
(2019/03/05)
-
- PYRROLO[2,3-C]PYRIDINE DERIVATIVE, PREPARATION METHOD THEREFOR, AND USE THEREOF IN MEDICINE
-
Disclosed are a pyrrolo[2,3-c]pyridine derivative, a preparation method therefor, and use thereof in medicine. Specifically, disclosed are a pyrrolo[2,3-c]pyridine derivative as represented by general formula (1), a preparation method therefor, a pharmaceutical composition comprising the derivative, as well as use thereof as a BRD4 inhibitor in the treatment of related diseases such as cancers, inflammations, chronic liver diseases, diabetes, cardiovascular diseases and AIDS, each substituent in general formula (I) being same as defined in the description.
- -
-
Page/Page column 73-74
(2018/08/03)
-
- An investigation into the role of 2,6-lutidine as an additive for the RuCl3-NaIO4 mediated oxidative cleavage of olefins to ketones
-
2,6-Lutidine has been identified as a beneficial additive for the oxidative cleavage of olefins to ketones by NaIO4 in the presence of catalytic RuCl3, improving the yield and shortening the reaction times. In the absence of 2,6-lutidine reactions stalled at the diol intermediate with incomplete conversion to the desired ketones. The reaction protocol described herein also avoids the use of harmful solvents such as CCl4 and DCE and is tolerant of a range of functional groups.
- Watson, David W.,Gill, Matthew,Kemmitt, Paul,Lamont, Scott G.,Popescu, Mihai V.,Simpson, Iain
-
supporting information
p. 4479 - 4482
(2018/11/23)
-
- COMBINATIONS OF HEPATITIS C VIRUS INHIBITORS
-
The present disclosure is generally directed to antiviral compounds, and more specifically directed to combinations of compounds which can inhibit the function of the NS5A protein encoded by Hepatitis C virus (HCV), compositions comprising such combinations, and methods for inhibiting the function of the NS5A protein.
- -
-
Page/Page column 559
(2015/02/02)
-
- CYCLOALKYL NITRILE PYRAZOLO PYRIDONES AS JANUS KINASE INHIBITORS
-
Compounds of formula I are provided, which are JAK inhibitors and are useful for the treatment of JAK-mediated diseases such as rheumatoid arthritis, asthma, COPD and cancer.
- -
-
Page/Page column 117
(2014/10/03)
-
- CYCLOALKYL NITRILE PYRAZOLO PYRIDONES AS JANUS KINASE INHIBITORS
-
The instant invention provides compounds of formula I which are JAK inhibitors, and as such are useful for the treatment of JAK-mediated diseases such as rheumatoid arthritis, asthma, COPD and cancer.
- -
-
Page/Page column 96; 97
(2014/10/03)
-
- HEPATITIS C INHIBITOR COMPOUNDS
-
A compound of formula (I) useful for the treatment or prevention of hepatitis C viral infection, (Formula (I)) wherein: X1 and X2 are each independently CRB or N; RB is H, (C1-6)alkyl, (C1-6/sub
- -
-
Page/Page column 34
(2013/03/26)
-
- CYCLIC BRIDGEHEAD ETHER DGAT1 INHIBITORS
-
The invention relates to compounds of formula (I): useful for treating disorders mediated by acyl coA-diacylglycerol acyl transferase 1 (DGAT1), e.g. metabolic disorders. The invention also provides methods of treating such disorders, and compounds and compositions etc. for their treatment.
- -
-
Paragraph 0402;0403
(2013/11/06)
-
- FLUOROPHENYL BICYCLIC HETEROARYL COMPOUNDS
-
The present invention provides a compound of formula (I); a method for manufacturing the compounds of the invention, and its use as a IGF-1R inhibitor. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
- -
-
Page/Page column 50
(2012/09/22)
-
- HYDROXY SUBSTITUTED ISOQUINOLINONE DERIVATIVES
-
The invention relates to compounds of formula (I): as defined in the application. Such compounds are suitable for the treatment of a disorder or disease which is mediated by the activity of MDM2 and/or MDM4, or variants thereof.
- -
-
Page/Page column 159
(2013/02/28)
-
- NOVEL SPIROHETEROCYCLIC COMPOUNDS AS MGLU5 ANTAGONISTS
-
The invention provides compounds having the general formula (I) wherein X is O or S; R1 is C, N, O or S; R1a is CH, CH2, N or NH; R2 is a bond, CH or CH2; m is 1, 2 or 3; n is 1 or 2; when n is 2 or m is 2 or 3, the ring containing R1 may be fused with a benzene ring; each --- represents a single or double bond provided that one double bond extends from the carbon atom to which R3-C≡C- is bonded and that no ring carbon atom bears two double bonds; and R3, R4 and R5 represent a wide range of substituents. These compounds are selective for the metabotropic mGlu5 receptor. They, their solvates, hydrates, enantiomers, diastereomers, N-oxides and pharmaceutically acceptable salts, and pharmaceutical compositions containing them, can be used to treat diseases or disorders of the lower urinary tract, especially neuromuscular dysfunctions of the lower urinary tract. They may also be useful for the treatment of migraine; for the treatment of gastroesophageal reflux disease (GERD); for the treatment of anxiety disorder; for the treatment of abuse, substance dependence and substance withdrawal disorder; for the treatment of neuropathic pain disorder; and for the treatment of fragile X syndrome disorders.
- -
-
Page/Page column 51
(2012/02/01)
-
- LIQUID CRYSTALLINE COMPOUND WITH NEGATIVE DIELECTRIC ANISOTROPY, LIQUID CRYSTAL COMPOSITION, AND LIQUID CRYSTAL DISPLAY DEVICE
-
A liquid crystal compound is provided that has excellent characteristics, such as a negatively large dielectric anisotropy. A liquid crystal composition containing the compound, and a liquid crystal display device containing the composition are also provi
- -
-
Page/Page column 33
(2011/02/17)
-
- ETHER DERIVATIVES OF BICYCLIC HETEROARYLS
-
The invention relates to compounds of formula (I), wherein the substituents are as defined in the specification; to processes for the preparation of such compounds; pharmaceutical compositions comprising such compounds; such compounds as a medicament; such compounds for the treatment of a proliferative disease
- -
-
Page/Page column 60-61
(2011/04/18)
-
- PHOSPHODIESTARASE INHIBITORS
-
The present invention relates to phosphodiesterase (PDE) type 4, phosphodiesterase (PDE) type 7 and dual PDE type 4 /PDE type 7 inhibitors. Compounds disclosed herein can be useful in the treatment, prevention, inhibition or suppression of CNS diseases, f
- -
-
Page/Page column 40
(2010/05/13)
-
- Design and synthesis of cell potent BACE-1 inhibitors: Structure-activity relationship of P1′ substituents
-
Using structure-guided design, hydroxyethylamine BACE-1 inhibitors were optimized to nanomolar Aβ cellular inhibition with selectivity against cathepsin-D. X-ray crystallography illuminated the S1′ residues critical to this effort, which culminated in compounds 56 and 57 that exhibited potency and selectivity but poor permeability and high P-gp efflux.
- Sealy, Jennifer M.,Truong, Anh P.,Tso, Luke,Probst, Gary D.,Aquino, Jose,Hom, Roy K.,Jagodzinska, Barbara M.,Dressen, Darren,Wone, David W.G.,Brogley, Louis,John, Varghese,Tung, Jay S.,Pleiss, Michael A.,Tucker, John A.,Konradi, Andrei W.,Dappen, Michael S.,Toth, Gergely,Pan, Hu,Ruslim, Lany,Miller, Jim,Bova, Michael P.,Sinha, Sukanto,Quinn, Kevin P.,Sauer, John-Michael
-
scheme or table
p. 6386 - 6391
(2010/06/11)
-
- Intramolecular schmidt reaction involving primary azidoalcohols under nonacidic conditions: Synthesis of indolizidine (-)-167B
-
(Chemical Equation Presented) A powerful intramolecular Schmidt reaction starting from primary azidoalcohols is reported. This approach involves a nonacidic activation of the alcohol via triflation. The synthetic potential offered by the mild reaction con
- Kapat, Ajoy,Nyfeler, Erich,Giuffredi, Guy T.,Renaud, Philippe
-
supporting information; experimental part
p. 17746 - 17747
(2010/04/01)
-
- LIQUID CRYSTAL COMPOUND HAVING NEGATIVE DIELECTRIC ANISOTROPY, LIQUID CRYSTAL COMPOSITION, AND LIQUID CRYSTAL DISPLAY DEVICE
-
A liquid crystal compound is provided that has excellent characteristics, such as a negatively large dielectric anisotropy. A liquid crystal composition containing the compound, and a liquid crystal display device containing the composition are also provi
- -
-
-
- TETRAHYDROBENZOTHIOPHENE DERIVATIVES
-
Compounds of a certain formula I, in which Ra and Rb have the meanings indicated in the description, are novel effective compounds with anti-proliferative and apoptosis inducing activity.
- -
-
Page/Page column 186
(2008/06/13)
-
- MELANOCORTIN RECEPTOR AGONISTS
-
The present invention relates to a compound of the following formula 1, pharmaceutically acceptable salt and isomer thereof effective as agonist of melanocortin receptor, and an agonistic composition of melanocortin receptor comprising the same as active ingredient.
- -
-
Page/Page column 28
(2008/06/13)
-
- PYRAZOLO (3, 4-B) PYRIDINE DERIVATIVES AS PHOSPHODIESTERASE INHIBITORS
-
The present invention relates to phosphodiesterase (PDE) type 4, phosphodiesterase (PDE) type 7 and dual PDE type 4 /PDE type 7 inhibitors. Compounds disclosed herein having the structure of Formura 1: can be useful in the treatment, prevention, inhibitio
- -
-
Page/Page column 86-87
(2008/12/07)
-
- Novel Angiogenesis inhibitors and pharmaceutical/cosmetic applications thereof
-
Novel derivatives of fumagalone have the general formula (I): and are useful angiogenes is inhibitors; these can be formulated into pharmaceutical compositions suited for human or veterinary medicine, or can be formulated into cosmetic compositions.
- -
-
Page/Page column 7; sheet 2
(2010/11/27)
-
- OXIME DERIVATIVE SUBSTITUTED HYDROXYETHYLAMINE ASPARTYL PROTEASE INHIBITORS
-
The invention relates to novel compounds and methods of treating diseases, disorders, and conditions associated with amyloidosis. Amyloidosis refers to a colletion of diseases, disorders, and conditions associated with abnormal deposition of A-beta protei
- -
-
Page/Page column 99-100
(2008/06/13)
-
- OXIME DERIVATIVE HYDROXYETHYLAMINE ASPARTYL-PROTEASE INHIBITORS
-
The invention relates to novel compounds and methods of treating diseases, disorders, and conditions associated with amyloidosis. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein.
- -
-
Page/Page column 104-105
(2010/02/15)
-
- INHIBITORS OF PHOSPHODIESTERASE TYPE-IV
-
The present invention relates to isoxazoline derivatives, which can be used as selective inhibitors of phosphodiesterase (PDE) type IV. In particular, compounds disclosed herein can be useful in the treatment of AIDS, asthma, arthritis, bronchitis, chronic obstructive pulmonary disease (COPD), psoriasis, allergic rhinitis, shock, atopic dermatitis, Crohn's disease, adult respiratory distress syndrome (ARDS), eosinophilic granuloma, allergic conjunctivitis, osteoarthritis, ulcerative colitis and other inflammatory diseases in a patient, particularly in humans. The present invention also relates to processes for the preparation of disclosed compounds, as well as pharmaceutical compositions thereof, and their use as phosphodiesterase (PDE) type IV inhibitors.
- -
-
Page/Page column 71-72
(2008/06/13)
-
- Improved Julia-Kocienski conditions for the methylenation of aldehydes and ketones
-
The scope of the methylenation of aldehydes and ketones under optimized Julia-Kocienski conditions is broadened by using 1-tert-butyl-1H-tetrazol-5- ylmethyl sulfone. Two different Barbier-type procedures are applied with NaHMDS at -78 °C or Cs2CO3 at 70 °C. The latter conditions are also adapted for the preparation of 1,2-disubstituted olefins and intramolecular olefination reactions.
- Aissa, Christophe
-
p. 360 - 363
(2007/10/03)
-
- HYDROGENATED BENZO (C) THIOPHENE DERIVATIVES AS IMMUNOMODULATORS
-
The invention relates to novel thiophene derivatives, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunosuppressive agents.
- -
-
Page/Page column 71
(2010/11/24)
-
- SUBSTITUTED HYDROXYETHYLAMINE ASPARTYL PROTEASE INHIBITORS
-
The invention relates to novel compounds and also to methods of treating at least one disease, disorder, or condition associated with amyloidosis using such compounds. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein.
- -
-
Page/Page column 283
(2008/06/13)
-
- 3,5-Bis(trifluoromethyl)phenyl sulfones in the direct Julia-Kocienski olefination
-
3,5-Bis(trifluoromethyl)phenyl (BTFP) sulfones 7 have been employed in the Julia-Kocienski olefination reaction with carbonyl compounds. Sulfones 7 are readily prepared in high yields (64-97%) from commercially available 3,5-bis(trifluoromethyl)thiophenol through an alkylation/oxidation two-step sequence. The stability of metalated BTFP sulfones has been studied and compared with heteroaryl benzothiazol-2-yl (BT), 1-phenyl-1H-tetrazol-5-yl (PT), and 1-tert-butyl-1H-tetrazol-5-yl (TBT) sulfones 9-11 under different reaction conditions. The Julia-Kocienski olefination between alkyl BTFP sulfones 7 and a wide variety of aldehydes affords the corresponding 1,2-disubstituted alkenes and dienes in good yields and stereoselectivities. This one-pot protocol can be performed using KOH at room temperature or the phosphazene bases P2-Et and P4-t-Bu at -78 °C or rt and has been successfully used in a high-yielding and stereoselective synthesis of various methoxylated stilbenes such as trimethylated resveratrol. These new reaction conditions for the Julia-Kocienski olefination reaction have been also studied with BT, PT, and TBT sulfones, giving poorer results. Methylenation of aliphatic and aromatic aldehydes, ketones, and 1,2-dicarbonyl compounds is carried out through the modified Julia olefination using BTFP methyl sulfone 7d to give terminal alkenes and dienes. Mechanistic studies of the olefination reaction between benzyl BTFP sulfone 7a and aromatic aldehydes performed by KOH-induced Smiles rearrangement of stereodefined syn- and anit-β-hydroxyalkyl BTFP sulfones indicate that the stereocontrol of the reaction is determined in the elimination step. 2005 American Chemical Society.
- Alonso, Diego A.,Fuensanta, Monica,Najera, Carmen,Varea, Montserrat
-
p. 6404 - 6416
(2007/10/03)
-
- SUBSTITUTED UREA AND CARBAMATE, PHENACYL-2-HYDROXY-3-DIAMINOALKANE, AND BENZAMIDE-2-HYDROXY-3-DIAMINOALKANE ASPARTYL-PROTEASE INHIBITORS
-
The invention relates to acetyl 2-hydroxy-1,3-diaminospirocyclohexanes and derivatives thereof that are useful in treating at least one disease, disorder, and condition associated with amyloidosis. Amyloidosis refers to a collection of diseases, disorders, and condition associated with abnormal deposition of A-beta protein.
- -
-
Page/Page column 367-368
(2010/02/14)
-
- SUBSTITUTED HYDROXYETHYLAMINE ASPARTYL PROTEASE INHIBITORS
-
The invention relates to novel compounds and also to methods of treating at least one disease, disorder, or condition associated with amyloidosis using such compounds. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein.
- -
-
Page/Page column 138
(2010/02/14)
-
- Radical Carboazidation: Expedient Assembly of the Core Structure of Various Alkaloid Families
-
A procedure for one-pot intermolecular radical addition of 2-iodoesters to terminal alkenes followed by azidation of the radical adduct has been developed. This sequential reaction represents an alkene carboazidation process. Its efficacy is demonstrated
- Panchaud, Philippe,Ollivier, Cyril,Renaud, Philippe,Zigmantas, Sarunas
-
p. 2755 - 2759
(2007/10/03)
-
- Total synthesis of cis and trans-hydroxyglimepiride: Active metabolite of glimepiride
-
Syntheses of trans-hydroxyglimepiride 2b, a human metabolite of the blood glucose lowering agent glimepiride 1 and its corresponding cis-stereoisomer 2a, are described.
- Gurjar, Mukund K.,Joshi, Ramesh A.,Chaudhuri, Siddhartha R.,Joshi, Shreerang V.,Barde, Anup R.,Gediya, Lalji K.,Ranade, Prasad V.,Kadam, Suresh M.,Naik, Sanjay J.
-
p. 4853 - 4855
(2007/10/03)
-
- [3,3] Sigmatropic rearrangement of some fluorinated 1,5-hexadienes
-
Fluorine atoms incorporated into 1,5-hexadiene molecule should influence the kinetic as well as the thermodynamic parameters of [3,3] sigmatropic rearrangement (Cope rearrangement). Within few decades is has been documented that this transformation proceeds in a concerted manner, rather than stepwise with some radical intermediates involved. Few new terminally fluorinated 1,5-hexadienes (compounds 3, 5A, 7, 9 and 5B) have been synthesized. The activation parameters of rearrangement have been determined and compared with those known for hydrocarbon analogues. While systems developing chair-like transition states (compounds 3 and 5) showed close similarity with hydrocarbon analogues (compound 1), those developing boat-like transition states (compounds 7, 9 and 5B) may proceed through radical stepwise mechanism. Computational studies of the transition states were carried out, showing that only ab initio methods (MP2 and especially DFT) can give approximate correlation with experimental data, whereas in the case of hydrocarbon analogues even simple semiempirical methods (AM1) were reliable enough to reproduce experimental results.
- Dolbier Jr., William R.,Palmer, Keith W.,Tian, Feng,Fiedorow, Piotr,Zaganiaczyk, Andrzej,Koroniak, Henryk
-
p. 1517 - 1532
(2007/10/03)
-
- A facile synthesis of spiro-cyclopentenones from various 1-alkynes and cyclic exo-methylene compounds by intermolecular Pauson-Khand reaction
-
Intermolecular Pauson-Khand reaction of various 1-alkynes with exo-methylene-piperidine and -cyclohexane derivatives was examined to give the title compounds in moderate to good yields.
- Ishizaki, Miyuki,Kasama, Yasuhiro,Zyo, Mieko,Niimi, Yuka,Hoshino, Osamu
-
p. 1439 - 1442
(2007/10/03)
-
- Asymmetric Baeyer - Villiger oxidations of 4-mono- and 4,4-disubstituted cyclohexanones by whole cells of engineered Escherichia coli
-
Whole cells of an Escherichia coli strain that overexpresses Acinetobacter sp. NCIB 9871 cyclohexanone monooxygenase have been used for the Baeyer-Villiger oxidations of a variety of 4-mono- and 4,4-disubstituted cyclohexanones. In cases where comparisons were possible, this new biocatalytic reagent provided lactones with chemical yields and optical purities that were comparable to those obtained from the purified enzyme or a strain of bakers' yeast that expresses the same enzyme. The efficient production of cyclohexanone monooxygenase in the E. coli expression system (ca. 30% of total soluble protein) allowed these oxidations to reach completion in approximately half the time required for the engineered bakers' yeast strain. Surprisingly, 4,4-disubstituted cyclohexanones were also accepted by the enzyme, and the enantioselectivities of these oxidations could be rationalized by considering the conformational energies of bound substrates along with the enzyme's intrinsic enantioselectivity. The enzyme expressed in E. coli cells also oxidized several 4-substituted cyclohexanones bearing polar substituents, often with high enantioselectivities. In the case of 4-iodocyclohexanone, the lactone was obtained in > 98% ee and its absolute configuration was assigned by X-ray crystallography. The crystal belongs to the monoclinic P21 space group with a = 5.7400(10), b = 6.1650(10), c = 11.377(2) A, b = 99.98(2)°, and Z = 2. Taken together, these results demonstrate the utility of an engineered bacterial strain in delivering useful chiral building blocks in an experimentally simple manner.
- Mihovilovic,Chen,Wang,Kyte,Rochon,Kayser,Stewart
-
p. 733 - 738
(2007/10/03)
-
- A useful α, α' - Annulation reaction of enamines
-
The reactions of a series of enamines generated from a range of cyclic ketones with chloromethyl and iodomethyl vinyl ketone have been studied. The principal products are bridged ring diketones. The four carbon bridge, bearing a 2-oxobutyl function, spans
- Frontier, Alison J.,Danishefsky, Samuel J.,Koppel, Gary A.,Meng, Dongfang
-
p. 12721 - 12736
(2007/10/03)
-
- Stereoselective Cyclization of 4-Substituted 5-Hexen-1-ols and Related Compounds by Benzeneselenenyl Triflate
-
Oxyselenylation of 4-substituted 5-hexen-1-ols 1 with benzeneselenenyl trifluoromethanesulfonate proceeds by intramolecular exo cyclization stereoselectively to give 3-substituted trans- or cis-2-(phenylselenenylmethyl)tetrahydropyrans 3.Formation of the trans isomers is favored when the substituents contain alkyl or phenyl substituents in the 4-position, whereas the cis isomers predominate when the substituents are alkoxyalkyl, alkoxyl, acyl, and hydroxyl.The mechanism of the trans and cis stereoselectivity is explained by steric and electronic effects in the phenylseleniranium intermediates, 7 and 8. - Key Words: Oxyselenenylation / Benzeneselenenyl triflate / Selenium compounds / Trifluoromethanesulfonate / Alkenols
- Inoue, Hirohumi,Murata, Shizuaki,Suzuki, Toshiyasu
-
p. 901 - 910
(2007/10/02)
-