Influence of α-Coordinating Groups of Aldehyde on E/Z-Selectivity and Use of Quaternary Ammonium Counter Ion For Enhanced E-Selectivity in Julia-Kocienski Reaction.

2021 ◽  
Author(s):  
rajendar goreti ◽  
Mintu Rehman ◽  
Sravya Surendran ◽  
Nagendra Siddavattam
Keyword(s):  
Transition State ◽  
Quaternary Ammonium ◽  
Reaction Condition ◽  
Counter Ion ◽  
Chelating Groups

A modified reaction condition for improved E-selectivity of olefin in Julia-Kocienski reaction of aldehydes having α-coordinating substituents is demonstrated. The chelating groups in aldehyde expected to stabilize syn-transition state (S7)...

scholarly journals Evaluation of Ion-pair Formation of Adefovir to Improve Permeation across Artificial and Biological Membranes

2018 ◽  
Vol 21 ◽  
pp. 160-170 ◽  
Author(s):  
Bahar Darsazan ◽  
Alireza Shafaati ◽  
Afshin Zarghi ◽  
Seyed Alireza Mortazavi
Keyword(s):  
Quaternary Ammonium ◽  
Adefovir Dipivoxil ◽  
Ion Pair ◽  
Pair Formation ◽  
Quaternary Ammonium Salts ◽  
Ammonium Salts ◽  
Apparent Permeability ◽  
Ion Pair Formation ◽  
Counter Ion ◽  
Everted Gut Sac

Purpose: Adefovir is an antiviral drug that exhibits high hydrophilic properties and negligible bioavailability (less than 12%). It is only applied in the form of the ester prodrug adefovir dipivoxil (ADV). The oral bioavailability of ADV is limited (32% to 45%) by its low permeability (Class 3) and biological conversion of the prodrug to adefovir. Ion-pair formation is considered as an alternative approach to a covalent prodrug (ADV) to enhance intestinal permeation of adefovir. Methods: The effect of various counter-ions (anionic, cationic and two quaternary ammonium salts) on the lipophilicity of adefovir was investigated by means of the n-octanol/buffer partitioning system, an in vitro transport model (PAMPA) and a biological membrane (everted gut sac). Results: Quaternary ammonium salts, cetylpyridinium chloride (CPC) and cetrimide enhanced the lipophilicity of adefovir 136- and 87-fold, respectively. The apparent permeability of adefovir in combination with CPC (counter-ion) was 2.5-fold greater than ADV permeability in the PAMPA model. The apparent permeability of adefovir-CPC (counter-ion) was 1.3-fold greater than that of adefovir dipivoxil permeability in a biologic membrane (everted gut sac). Conclusion: These results suggest that the adefovir-CPC ion-paired system has potential for improving the permeation of adefovir across the intestinal membrane. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Exploring the Scope of Tandem Palladium and Isothiourea Relay Catalysis for the Synthesis of α-Amino Acid Derivatives

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2463
Author(s):  
Jacqueline Bitai ◽  
Alexandra M. Z. Slawin ◽  
David B. Cordes ◽  
Andrew D. Smith
Keyword(s):  
Amino Acid ◽  
Transition State ◽  
Quaternary Ammonium ◽  
Palladium Catalyst ◽  
Quaternary Ammonium Salts ◽  
Sigmatropic Rearrangement ◽  
Ammonium Salts ◽  
Amino Acid Derivatives ◽  
Substitution Pattern

The scope and limitations of a tandem N-allylation/[2,3]-rearrangement protocol are investigated through the incorporation of a variety of functional groups within an allylic phosphate precursor. This method uses readily accessible N,N-dimethylglycine aryl esters and functionalized allylic phosphates, forming quaternary ammonium salts in situ in the presence of a palladium catalyst. Subsequent enantioselective [2,3]-sigmatropic rearrangement, promoted by the chiral isothiourea tetramisole, generates α-amino acid derivatives with two contiguous stereocenters. The incorporation of electron-withdrawing ester and amide groups gave the best results, furnishing the desired products in moderate to good yields (29–70%), with low diastereocontrol (typically 60:40 dr) but high enantioselectivity (up to 90:10 er). These results indicate that substrate–catalyst interactions in the proposed transition state are sensitive to the substitution pattern of the substrates.

The reactions of simple dimethylallylamines with dimethyl acetylenedicarboxylate. Formation of 1-dimethylamino-2-allylmaleates via formal allyl transfer

1988 ◽  
Vol 66 (7) ◽  
pp. 1686-1694 ◽  
Author(s):  
Adrian L. Schwan ◽  
John Warkentin
Keyword(s):  
Proton Transfer ◽  
Transition State ◽  
Carbonyl Group ◽  
Quaternary Ammonium ◽  
Methyl Groups ◽  
Dimethyl Acetylenedicarboxylate ◽  
Tertiary Amines ◽  
Reversible Formation ◽  
Zwitterionic Intermediate ◽  
Membered Transition State

Tertiary amines bearing two methyl groups and an allylic substituent (X) react with dimethyl acetylenedicarboxylate (DMAD) to afford the corresponding 1-dimethylamino-2-X′ maleates, in which X′ is the allylic isomer of X. The mechanism postulated involves reversible formation of a zwitterion by attack of the amine at an sp-carbon of DMAD. The zwitterion then undergoes intramolecular allyl transfer, through a 6-membered transition state. Evidence for a zwitterionic intermediate (quaternary ammonium allenolate) includes capture of the allenolate centre by intramolecular addition to a carbonyl group and by proton transfer from chloroform.

Catalyst- and oxidant-free electrochemical para-selective hydroxylation of N-arylamides in batch and continuous-flow

2020 ◽  
Vol 22 (19) ◽  
pp. 6437-6443
Author(s):  
Cheng-Kou Liu ◽  
Meng-Yi Chen ◽  
Xin-Xin Lin ◽  
Zheng Fang ◽  
Kai Guo
Keyword(s):  
Ammonium Salt ◽  
Quaternary Ammonium ◽  
Continuous Flow ◽  
Quaternary Ammonium Salt ◽  
Selective Hydroxylation

A catalyst-, oxidant-, acidic solvent- and quaternary ammonium salt-free electrochemical para-selective hydroxylation of N-arylamides at rt in batch and continuous-flow was developed.

Memapsin 2, a drug target for Alzheimer's disease

2003 ◽  
Vol 70 ◽  
pp. 213-220 ◽  
Author(s):  
Gerald Koelsch ◽  
Robert T. Turner ◽  
Lin Hong ◽  
Arun K. Ghosh ◽  
Jordan Tang
Keyword(s):  
Crystal Structure ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transition State ◽  
Amyloid Precursor Protein ◽  
Therapeutic Target ◽  
Drug Target ◽  
Aspartic Protease ◽  
Precursor Protein ◽  
Memapsin 2

Mempasin 2, a ϐ-secretase, is the membrane-anchored aspartic protease that initiates the cleavage of amyloid precursor protein leading to the production of ϐ-amyloid and the onset of Alzheimer's disease. Thus memapsin 2 is a major therapeutic target for the development of inhibitor drugs for the disease. Many biochemical tools, such as the specificity and crystal structure, have been established and have led to the design of potent and relatively small transition-state inhibitors. Although developing a clinically viable mempasin 2 inhibitor remains challenging, progress to date renders hope that memapsin 2 inhibitors may ultimately be useful for therapeutic reduction of ϐ-amyloid.

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