23601-49-2Relevant academic research and scientific papers
Structure Property Relationships of Carboxylic Acid Isosteres
Lassalas, Pierrik,Gay, Bryant,Lasfargeas, Caroline,James, Michael J.,Tran, Van,Vijayendran, Krishna G.,Brunden, Kurt R.,Kozlowski, Marisa C.,Thomas, Craig J.,Smith, Amos B.,Huryn, Donna M.,Ballatore, Carlo
, p. 3183 - 3203 (2016/05/19)
The replacement of a carboxylic acid with a surrogate structure, or (bio)-isostere, is a classical strategy in medicinal chemistry. The general underlying principle is that by maintaining the features of the carboxylic acid critical for biological activity, but appropriately modifying the physicochemical properties, improved analogs may result. In this context, a systematic assessment of the physicochemical properties of carboxylic acid isosteres would be desirable to enable more informed decisions of potential replacements to be used for analog design. Herein we report the structure-property relationships (SPR) of 35 phenylpropionic acid derivatives, in which the carboxylic acid moiety is replaced with a series of known isosteres. The data set generated provides an assessment of the relative impact on the physicochemical properties that these replacements may have compared to the carboxylic acid analog. As such, this study presents a framework for how to rationally apply isosteric replacements of the carboxylic acid functional group.
Imino 1,2-Wittig rearrangement of hydroximates and its application to synthesis of cytoxazone
Miyata, Okiko,Koizumi, Tomoko,Asai, Hiroshi,Iba, Ryuichi,Naito, Takeaki
, p. 3893 - 3914 (2007/10/03)
The imino 1,2-Wittig rearrangement of hydroximates provides a novel method for the construction of 2-hydroxyoxime ethers. Upon treatment with LDA, Z-hydroximates smoothly underwent stereoselective rearrangement to give Z-2-hydroxyoxime ethers in good yield, which were converted into amino alcohols. On the other hand, the rearrangement of E-hydroximates gave a mixture of E- and Z-2-hydroxyoxime ethers. This method was successfully applied to a practical synthesis of cytoxazone.
Synthesis of ketones and aldehydes via reactions of Weinreb-type amides on solid support
Dinh, Tam Q.,Armstrong, Robert W.
, p. 1161 - 1164 (2007/10/03)
Ketones and aldehydes were formed in low to good yields in reactions of Weinreb-type amides on solid support and no overaddition occurred.
Preparation and thermal decomposition of N,N'-diacyl-N,N'-dialkoxyhydrazines: Synthetic applications and mechanistic insights
De Almeida, Mauro V.,Barton, Derek H. R.,Bytheway, Ian,Ferreira, J. Albert,Hall, Michael B.,Liu, Wansheng,Taylor, Dennis K.,Thomson, Lisa
, p. 4870 - 4874 (2007/10/02)
Oxidation of various O-alkyl hydroxamates 1 where R1 was a keto-methoxime, benzoyl, aryl, or alkyl group with ceric ammonium nitrate (CAN) or nickel peroxide (NiO2·H2O) leads to the corresponding esters in high yield. This augurs well for the facile synthesis of highly hindered esters. Dimers of type 2 were identified as intermediates in these oxidations, and a combination of experimental and theoretical results suggest that these dimers decompose in a stepwise 1,1-elimination manner via intermediate nitrenes to furnish the esters and not via a stepwise 1,2-elimination sequence as previously thought.
A new synthesis of nitriles from N-alkoxyimidoyl halides with zinc
Sakamoto,Mori,Takizawa,Kikugawa
, p. 750 - 752 (2007/10/02)
Both aliphatic and aromatic nitriles are obtained from the corresponding N-methoxy-, N-benzyloxy- or N-tert-butoxyimidoyl halides with zinc in a acetic acid/dimethylformamide mixture (1:1).
Electrophilic Aromatic Substitution with N-Methoxy-N-acylnitrenium Ions Generated from N-Chloro-N-methoxyamides: Syntheses of Nitrogen Heterocyclic Compounds Bearing a N-Methoxyamide Group
Kawase, Masami,Kitamura, Takahiro,Kikugawa, Yasuo
, p. 3394 - 3403 (2007/10/02)
N-Methoxy-N-acylnitrenium ions (II), generated by treatment of N-chloro-N-methoxyamides with silver carbonate in trifluoroacetic acid, react with arenes to give N-aryl-N-methoxyamides in good yields.In the case of the intramolecular cyclization of N-chloro-N-methoxy-2-phenylacetamides, the mode of cyclization is highly dependent on the nature of ortho or para substituent groups.Nitrenium ions II can primarily attack three positions (C-1, C-2, and C-6) of a phenyl ring.Normally II attack C-6.On the other hand, when the ortho position was occupied with a substituent group, II attacked both C-2 and C-6, in the former case followed by a 1,2-substituent migration, which was proved by a deuterium labeling experiment.Especially, when a methoxy group is substituted on ortho or para position, II attack C-1 due to the effect of the electron-releasing methoxy group to give spiro dienone compounds 39.A general discussion of the utility and mechanistic details of these reactions is presented.
N-ALKOXY-N-ACYLNITRENIUM IONS IN INTRAMOLECULAR AROMATIC ADDITION REACTIONS
Glover, Stephen A.,Goosen, Andre,McCleland, Cedric W.,Schoonraad, Johan L.
, p. 2577 - 2592 (2007/10/02)
N-alkoxy-N-acylnitrenium ions are generated by treatment of N-alkoxy-N-chloroamides with silver ions in ethereal solvents.These intermediates readily cyclise onto aromatic nuclei on alkoxy side-chains to give benzoxazines and benzoxazepines and on the acyl side-chains to give γ, δ and ε benzolactams.Spirane products are formed by ipso addition when a 4-methoxy substituent is present on the side-chain aromatic rings.The yields and regioselectivities of these reactions have been ascribed to different transition structures for cyclisation onto the acyl and alkoxy side-chains which involve respectively an exocyclic and endocyclic N-O ?-bond.Evidence for this exeptionally high ?-bond character has been obtained from MNDO calculations which predict a ?-bond order of 0.9 and a rotational barrier of 29.7 kcalmol-1
