- Conformationally Defined Analogs of Prolylamides. trans-Prolyl Peptidomimetics
-
The cis and trans conformations of prolylamides are both energetically accessible, in contrast to the peptide bonds of the remaining mammalian amino acids.The synthesis of a rigid, conformationally defined peptidomimetic of the trans-prolylamide bond has been developed in this study, and illustrative leucinylproline derivatives (4, 10a, 10b, and 11) were assayed for their abilities to inhibit the peptidyl prolyl isomerase activity of recombinant human FK-binding protein 12 (FKBP 12).These trans-prolyl peptidomimetics possess a trans-substituted alkene in place of the proline peptide bond and were synthesized via a six step sequence culminating in the selective addition of isobutylmagnesium bromide to 2(E)-(2-oxoethylidene)-1-methylcyclopentanecarboxylate (9).Synthesis of the dipeptide analogs was accomplished in six steps with a 20percent overall yield.Elaboeation of the dipeptide analog gave the Leu-Pro-tyrosyl tripeptide analog in three additional steps.The tripeptide mimic 4 proved to be a potent inhibitor of the prolyl isomerase activity of recombinant hFKBP 12, exhibiting an inhibition constant (Ki) of 8.6 μM; the dipeptidomimetics possessed a modest capacity for isomerase inhibition with inhibition constants ranging from 127 μM for the α-enone analog 11 to 730 and 1390 μM for the allylic alcohol mimetics 10a and 10b, respectively.
- Andres, Charles J.,Macdonald, Timothy L.,Ocain, Timothy D.,Longhi, Daniel
-
-
Read Online
- Preparation method of 2, 2-dimethyl cyclopentanone
-
The invention discloses a preparation method of 2, 2-dimethyl cyclopentanone, which comprises the following steps: methylating 2-methoxycarbonyl cyclopentanone to obtain a methylated product 2-methyl-2-methoxycarbonyl cyclopentanone, carrying out keto-carbonyl protection on the methylated product to obtain a protected product 2-methyl-2-methoxycarbonyl cyclopentanone ketal, carrying out ester group reduction on the protection product to obtain an alcohol product 2-hydroxymethyl-2-methyl cyclopentanone ketal, carrying out deprotection on the alcohol product under an acidic condition to obtain a deprotection product 2-hydroxymethyl-2-methyl cyclopentanone, and brominating the deprotection product to obtain 2-bromomethyl-2-methyl cyclopentanone. All raw materials adopted by the method are low in cost and easy to obtain in the market, and reactions in all steps are conventional reactions and easy to implement; the process is simple, mild in reaction condition and easy to operate; the reaction time is short, control is easy, the yield of each step is 90% or above, and industrial large-scale production is easy to achieve.
- -
-
Paragraph 0017
(2021/06/23)
-
- Preparation method of metconazole (by machine translation)
-
The method comprises the following steps: 2 - (2 - chlorobenzylidene) 2 - 2 -methylcyclopentanone and p-chlorobenzaldehyde react to obtain an epoxide; the epoxide reacts with triazole to obtain an epoxide; and the epoxide is reacted with triazole to obtain an open-loop product; and the ring-opening product 4 - is subjected -2 to 2 - catalytic hydrogenation to obtain the 2 - myclobutanil . 4 - beta-(4 -chlorbenzydrospirone; 5 -2 -5 -chlorobenzyl) 5 - and methylcyclopentanone react. Corey-Chayyyysky is obtained. The preparation method is low in cost, easy to obtain in the market; the reaction steps are all conventional reactions, reaction steps are simple, implementation; process is simple, reaction conditions are mild, operation; conversion rate is high, reaction time is short, control, and industrialization production. (by machine translation)
- -
-
Paragraph 0052-0054
(2019/10/01)
-
- SULFONYLCYCLOALKYL CARBOXAMIDE COMPOUNDS AS TRPA1 MODULATORS
-
The invention is concerned with the compounds of formula (I): and pharmaceutically acceptable salts thereof. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula I as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.
- -
-
Paragraph 0165; 0278; 0279; 0280; 0281; 0282
(2018/02/28)
-
- Chemo-, regio-, and stereo-selective perfluoroalkylations by a Grignard complex with zirconocene
-
The synthesis of highly reactive perfluoroalkyl Grignard reagents with early transition metal zirconocene complexes and their new types of highly chemo-, regio-, and stereo-selective perfluoroalkylation reactions are reported with epoxides in particular. The zirconocene complex is advantageous in activating the perfluoroalkyl Grignard species. The zirconocene·Grignard complexes were clarified by DOSY. Both 1H and 19F DOSY analyses show that the addition of MAO and dioxane to the mixture of RFMgCl and Cp2ZrCl2 connects Cp2Zr and RFMg to generate the zirconocene/perfluoroalkyl-Grignard/dioxane complex.
- Fujiu, Motohiro,Negishi, Kazuyuki,Guang, Jie,Williard, Paul G.,Kuroki, Shigeki,Mikami, Koichi
-
supporting information
p. 19464 - 19468
(2015/11/27)
-
- Catalytic asymmetric intramolecular homologation of ketones with α-diazoesters: Synthesis of cyclic α-Aryl/Alkyl β-ketoesters
-
A catalytic asymmetric intramolecular homologation of simple ketones with α-diazoesters was firstly accomplished with a chiral N,N′-dioxide-Sc(OTf)3 complex. This method provides an efficient access to chiral cyclic α-aryl/alkyl β-ketoesters containing an all-carbon quaternary stereocenter. Under mild conditions, a variety of aryl- and alkyl-substituted ketone groups reacted with α-diazoester groups smoothly through an intramolecular addition/rearrangement process, producing the β-ketoesters in high yield and enantiomeric excess.
- Li, Wei,Tan, Fei,Hao, Xiaoyu,Wang, Gang,Tang, Yu,Liu, Xiaohua,Lin, Lili,Feng, Xiaoming
-
supporting information
p. 1608 - 1611
(2015/01/30)
-
- Electrochemical reduction of 1-bromomethyl-2-oxocycloalkane-1-carboxylates at silver cathodes in dimethylformamide: One-carbon ring-expansion reactions
-
Cyclic voltammetry and controlled-potential (bulk) electrolysis have been employed to investigate the separate electrochemical reductions of methyl 1-bromomethyl-2-oxocyclopentane-1-carboxylate (1) and ethyl 1-bromomethyl-2-oxocyclohexane-1-carboxylate (2) at silver cathodes in dimethylformamide (DMF) containing 0.10 M tetramethylammonium tetrafluoroborate (TMABF4). Oneelectron reductive cleavage of the carbon-bromine bond of each substrate yields a radical intermediate that undergoes a ring-expansion reaction, followed by hydrogen-atom abstraction from the solvent, to afford methyl 3-oxocyclohexane-1-carboxylate (3a) and ethyl 3-oxocycloheptane-1-carboxylate (3b), respectively, in good yield. Each substrate gives rise to three other products: (a) a debrominated analogue of each starting material, (b) a dimeric species formed via radical coupling, and (c) a species possessing an ester group extended by one carbon atom. Electrolyses of 1 and 2 done in the presence of D2O have revealed that carbanion intermediates result in small amounts from two-electron cleavage of carbon-bromine bonds. A mechanistic scheme, involving both radicals and carbanions, is proposed to account for the formation of the various products.
- Wappes, Ethan A.,Mubarak, Mohammad S.,Peters, Dennis G.
-
p. G122 - G127
(2015/04/14)
-
- A short formal total synthesis of (±)-hirsutic acid
-
A short formal total synthesis of (±)-hirsutic acid is described using a Claisen rearrangement and a radical cascade as the key steps. The radical sequence involves an intermolecular addition of a radical derived from a xanthate followed by a cyclization and transfer of the xanthate group.
- Revol, Guillaume,Fuchs, Christian,Zard, Samir Z.
-
p. 927 - 931
(2013/02/22)
-
- A systematic study of the solid state and solution phase conformational preferences of β-peptides derived from C(3)-alkyl substituted transpentacin derivatives
-
The solid state and solution phase conformational preferences of a homologous series of β-peptides derived from a range of 2-amino-3-alkylcyclopentanecarboxylic acid residues have been investigated using a variety of spectroscopic and crystallographic techniques. These studies indicate that C(3)-alkyl substitution trans to the amino group on the cyclopentane backbone is tolerated by the established 12-helix secondary structural preference of the parent pentamer and hexamer derived from 2-aminocyclopentanecarboxylic acid (transpentacin) residues in both the solid state and solution phase. Evidence for the alternative turn type conformation identified for the C(3)-unsubstituted tetramer was not observed in the C(3)-alkyl substituted derivatives, consistent with the alkyl substituent anti to the amino functionality destabilising this motif. These results suggest that oligomers based around the transpentacin scaffold may be amenable to further elaboration at C(3) anti to the amino group with retention of the secondary structure.
- Abraham, Elin,Claridge, Timothy D.W.,Davies, Stephen G.,Odell, Barbara,Roberts, Paul M.,Russell, Angela J.,Smith, Andrew D.,Smith, Lorna J.,Storr, Helen R.,Sweet, Miles J.,Thompson, Amber L.,Thomson, James E.,Tranter, George E.,Watkin, David J.
-
experimental part
p. 69 - 100
(2011/04/18)
-
- Dynamic chirality of (E)-5-cyclononen-1-one and its enolate
-
It has been found that (E)-5-cyclononen-1-one (2a) exhibits marginal planar chirality owing to an insufficient topological constraint, whereas the enolates 3 derived from 2a show robust planar chirality. Enantioenriched enolates are easily prepared by enzymatic hydrolysis, and they show an ability to serve as chiral nucleophiles.
- Tomooka, Katsuhiko,Ezawa, Takayuki,Inoue, Hiroko,Uehara, Kazuhiro,Igawa, Kazunobu
-
supporting information; scheme or table
p. 1754 - 1756
(2011/04/15)
-
- Environmentally friendly TPDS-mediated free radical ring expansion of α-haloalkyl cyclic β-keto esters
-
Reactivities of tetraphenyldisilane (TPDS), tris(trimethylsilyl)silane, and tributyltin hydride in the radical ring expansion of α-haloalkyl cyclic β-keto esters were examined. Among these reagents, TPDS was found most effective for the preparation of medium-sized cyclic compounds in terms of yields and ring-expansion/reduction selectivity.
- Sugi, Masaaki,Togo, Hideo
-
p. 3171 - 3175
(2007/10/03)
-
- On the mechanism of the intramolecular samarium barbier reaction. Probes for formation of radical and organosamarium intermediates
-
A new type of mechanistic probe for the intramolecular samarium Barbier reaction has been designed, and two different probe substrates have been investigated in detail. Remarkably, no unambiguous evidence could be obtained in favor of any of the obvious intermediates (free alkyl or alkoxy radicals, ketyls, organosamarium species) that are postulated for this reaction. Several possibilities for modified mechanisms are suggested.
- Curran, Dennis P.,Gu, Xin,Zhang, Wei,Dowd, Paul
-
p. 9023 - 9042
(2007/10/03)
-
- Chiral Synthesis via Organoboranes. 42. Selective Reductions. 57. Efficient Kinetic Resolution of Representative α-Tertiary Ketones with B-Chlorodiisopinocampheylborane
-
Kinetic resolution of racemic α-tertiary ketones with 0.5-0.6 molar equiv of B-chlorodiisopinocampheylborane provides the product alcohols in very high diastereomeric and enantiomeric excess, with the unreacted ketone recovered in very high ee.For example, ethyl 1-methyl-2-oxocyclopentane- and cyclohexanecarboxylates are partially reduced to recover the ketone in 91 to >/=99percent ee and the product alcohols in up to 94percent de, with >90percent ee for the major diastereomer.Bicyclic ketones, such as 1-methyl- and 1-ethylnorcamphor, camphor, and camphenilone, are readily resolved to provide the ketone in 92 to >/=99percent ee, with the product alcohol recovered in high de and ee.Dihydrospirooctane-2,2'(3'H)-furan>-3-one is resolved to provide the ketone in >/=99percent ee and the product alcohol in >/=99percent de.In all the cases studied, the R-isomer of the ketone is recovered when dIpc2BCl is used for kinetic resolution, while lIpc2BCl provides the S-ketone.Optimum conditions for obtaining the product alcohol, or the ketone, or both, in very high yields and ee have been established.
- Ramachandran, P. Veeraraghavan,Chen, Guang-Ming,Brown, Herbert C.
-
-