The design and synthesis of nonpeptide compounds as mimics of a conformation of methionine-enkephaline

1982 ◽  
Vol 60 (8) ◽  
pp. 1019-1029 ◽  
Author(s):  
Patrice C. Belanger ◽  
Claude Dufresne ◽  
John Scheigetz ◽  
Robert N. Young ◽  
James P. Springer ◽  
...  
Keyword(s):  
Double Bond ◽  
Computer Modeling ◽  
High Yield ◽  
Side Chain ◽  
Active Conformation ◽  
Methionine Enkephalin ◽  
Design And Synthesis ◽  
Structural Template ◽  
Subsequent Addition

A model for the active conformation of methionine-enkephalin containing a β-turn was derived from computer modeling. Using a trans-perhydronaphthalene as a structural template and a mimic of the β-turn, target compounds were designed and synthesized. Thus, a key intermediate, trans-3-oxo-5β-formamidomethyl-8a-phenylmethylperhydronaphthalene, was prepared by two different routes from cyclohexanone.The addition of a methionine-like side-chain to this key intermediate was best achieved by a reaction with the anion of methyl 2-trimethylsilyl-4-methylthiobutanoate. This led to the preparation of an exo-tetrasubstituted double bond in high yield. Subsequent addition of tyrosine through coupling with the 5β-aminomethyl group provided the desired perhydronaphthalene mimics of met-enkaphalin.

scholarly journals Synthesis of [1,4]Oxathiepino[5,6-b]quinolines via Base-Mediated Intramolecular Hydroalkoxylation

SynOpen ◽  
2022 ◽  
Vol 06 (01) ◽  
pp. 7-10
Author(s):  
Morteza Shiri ◽  
Maryam-Sadat Tonekaboni ◽  
Zahra Tanbakouchian ◽  
Soma Majedi
Keyword(s):  
Double Bond ◽  
Hydroxyl Group ◽  
High Yield ◽  
Formyl Group ◽  
Bond Yields ◽  
Terminal Double Bond ◽  
Subsequent Addition

AbstractA base-mediated intramolecular hydroalkoxylation that was used to prepare a series of seven-membered S,O-heterocycles is described. 2-Thiopropargyl-3-hydroxymethyl quinolines were prepared starting from 2-mercaptoquinoline-3-carbaldehydes, via S-propargylation and reduction of a formyl group. Interestingly, 2-mercaptopropargyl-3-hydroxymethyl quinolines were converted into the corresponding oxathiepinoquinolines in the presence of t-BuOK. It is proposed that the S-propargyl moiety, in the presence of base, is converted into its allenyl isomer; subsequent addition of a hydroxyl group to the terminal double bond yields the 3-methyl-5H-[1,4]oxathiepino[5,6-b]quinoline in good to high yield. Notably, the procedure is adaptable to the conversion of N-propargyl indole-2-methanol into the corresponding intramolecular hydroalkoxylation product.

Preparation of exo-6-benzyl-exo-2-(m-hydroxyphenyl)-1-dimethylaminomethylbicyclo[2.2.2.]octane. A non-peptide mimic of enkephalins

1986 ◽  
Vol 64 (8) ◽  
pp. 1514-1520 ◽  
Author(s):  
Patrice C. Bélanger ◽  
Claude Dufresne
Keyword(s):  
Computer Modeling ◽  
Alder Reaction ◽  
Diels Alder ◽  
Grignard Reaction ◽  
Biological Testing ◽  
Active Conformation ◽  
Diels Alder Reaction ◽  
Peptide Mimic ◽  
Weak Activity ◽  
Structural Template

A model for the active conformation of methionine enkephalin was derived from computer modeling. From this model, a target was designed and synthesized using bicyclo[2.2.2]octane as a structural template. Thus, a key intermediate, exo-6-benzoyl-1-carboethoxybicyclo[2.2.2]-2-octene was prepared via a Diels–Alder reaction using ethyl dihydrobenzoate and phenylvinylketone. It was subsequently modified to exo-6-benzyl-1-dimethylaminobicyclo[2.2.2]-2-octene. This intermediate was hydroborated and oxidized to the ketone on which the second aromatic group was introduced using a Grignard reaction, eventually giving rise to the desired target, exo-6-benzyl-exo-2-(m-hydroxyphenyl)-1-dimethylaminobicyclo[2.2.2]octane. Biological testing demonstrated weak activity with this compound.

scholarly journals S-Fluorenylmethyl protection of the cysteine side chain upon N α-Fmoc deprotection

2012 ◽  
Vol 8 ◽  
pp. 2149-2155 ◽  
Author(s):  
Johannes W Wehner ◽  
Thisbe K Lindhorst
Keyword(s):  
Double Bond ◽  
High Yield ◽  
Side Chain ◽  
Exocyclic Double Bond ◽  
Fluorenylmethyl Protection

Deprotection of an N α-Fmoc-protected glycocysteine derivative 7 with an excess of morpholine unexpectedly led to the fluorenylmethyl-protected thioether 8 in high yield. The suggested mechanism for this reaction comprises the addition of the cysteine thiolate on the exocyclic double bond of dibenzofulvene, which is formed during Fmoc deprotection. The influence of base concentration on this transprotection reaction was studied.

Computer Modeling-Assisted Design And Synthesis Of Flavonols Derivatives As Proteasome Inhibitors

Planta Medica ◽  
2016 ◽  
Vol 82 (05) ◽  
Author(s):  
KY Orabi ◽  
MS Abaza ◽  
KA ElSayed ◽  
AY Elnagar ◽  
SI Faggal ◽  
...  
Keyword(s):  
Computer Modeling ◽  
Proteasome Inhibitors ◽  
Design And Synthesis

A Novel Scheme for the Synthesis of 21-Acetoxypregna-1,4,9(11)-triene- 17α,21-diol-3,20-dione from 9α-Hydroxyandrostenedione

2020 ◽  
Vol 16 (5) ◽  
pp. 606-610
Author(s):  
Nguyen T. Diep ◽  
Luu D. Huy
Keyword(s):  
Double Bond ◽  
Chemical Synthesis ◽  
Economic Efficiency ◽  
Final Stage ◽  
Side Chain ◽  
Entire Process ◽  
Drug Synthesis ◽  
First Time

Background: Vietnam currently imports up to 90% of the pharmaceuticals it consumes and 100% of the steroid-based pharmaceuticals. The ability for efficient chemical synthesis of the steroids could create commercial opportunities to address this issue. Synthesis of 21-acetoxypregna-1,4,9(11)- triene-17α,21-diol-3,20-dione is considered a key intermediate in the scheme of steroidal drug synthesis. Previous synthesis attempts of such steroids (corticoids) introduce a double bond at C-1(2) in the final stage of synthesis, which delivers a poor yield and reduces the economic efficiency of the process. Objective: To study and develop a novel and effective method for the synthesis of 21-acetoxypregna- 1,4,9(11)-triene-17α,21-diol-3,20-dione. Methods: Using 9α-hydroxyandrostenedione as a substrate chemical synthesis was performed as follows: pregnane side chain construction at C-17 (acetylene method), introduction of C-1(2) double bond (using SeO2), epimerization of C-17 (via 17-ONO2 ester) and Stork’s iodination. Results: 21-acetoxypregna-1,4,9(11)-triene-17α,21-diol-3,20-dione was prepared from 9α- hydroxyandrostenedione with an improved yield compared to previous attempts. Conclusion: Here, 21-acetoxypregna-1,4,9(11)-triene-17α,21-diol-3,20-dione has been synthesized from 9α-hydroxyandrostenedione based on a novel, effective and commercially feasible scheme. The introduction of the C-1(2) double bond at an earlier stage of the synthesis has increased the economic efficiency of the entire process. For the first time, the indirect epimerization mechanism has been clarified along with the configuration of the C-17 stereo-center which has been confirmed using NOESY data.

Critical Review of Biotransformational Studies on Steroids by Using Culture of Cunninghamella blakesleeana

2021 ◽  
Vol 18 ◽  
Author(s):  
Azizuddin ◽  
Muhammad Iqbal ◽  
Syed Ghulam Musharraf
Keyword(s):  
Double Bond ◽  
Critical Review ◽  
Structural Modification ◽  
Bond Formation ◽  
Environmentally Friendly ◽  
Side Chain ◽  
Synthetic Compounds ◽  
Efficient Approach ◽  
Cunninghamella Blakesleeana ◽  
Different Strains

: For several decades, biotransformational studies on steroidal compounds have gained a lot of attention because it is an efficient approach for the structural modification of complicated natural or synthetic compounds with high regio-, chemo- and stereoselectivity at environmentally friendly conditions. This review summarizes the use of different strains of Cunninghamella blakesleeana for the biotransformation of sixteen steroids 1-16 into a variety of transformed products. The transformed products may be important as a drug or precursor for the production of important pharmaceuticals. The types of reactions performed by C. blakesleeana include hydroxylation, epoxidation, reduction, demethylation, oxidation, glycosidation, double bond formation, side-chain degradation, isomerisation and opening of an isoxazol ring, which would be difficult to produce by traditional synthesis.

scholarly journals Cathodic hydrodimerization of nitroolefins

2015 ◽  
Vol 11 ◽  
pp. 1163-1174 ◽  
Author(s):  
Michael Weßling ◽  
Hans J Schäfer
Keyword(s):  
Double Bond ◽  
Nitro Group ◽  
Bond Formation ◽  
Cathodic Reduction ◽  
High Yield ◽  
Easy Access ◽  
Electrolysis Cell ◽  
Aldehydes And Ketones ◽  
Nef Reaction

Nitroalkenes are easily accessible in high variety by condensation of aldehydes with aliphatic nitroalkanes. They belong to the group of activated alkenes that can be hydrodimerized by cathodic reduction. There are many olefins with different electron withdrawing groups used for cathodic hydrodimerization, but not much is known about the behaviour of the nitro group. Synthetic applications of this group could profit from the easy access to nitroolefins in large variety, the C–C bond formation with the introduction of two nitro groups in a 1,4-distance and the conversions of the nitro group by reduction to oximes and amines, the conversion into aldehydes and ketones via the Nef reaction and base catalyzed condensations at the acidic CH bond. Eight 1-aryl-2-nitro-1-propenes have been electrolyzed in an undivided electrolysis cell to afford 2,5-dinitro-3,4-diaryl hexanes in high yield. The 4-methoxy-, 4-trifluoromethyl-, 2-chloro- and 2,6-difluorophenyl group and furthermore the 2-furyl and 2-pyrrolyl group have been applied. The reaction is chemoselective as only the double bond but not the nitro group undergoes reaction, is regioselective as a ß,ß-coupling with regard to the nitro group and forms preferentially two out of six possible diastereomers as major products.

Migration of the Double Bond in the Side Chain of Sterols with Iodine.

1970 ◽  
Vol 35 (12) ◽  
pp. 4145-4148 ◽  
Author(s):  
Nobuo Ikekawa ◽  
Yasushi Honma ◽  
Naoko Morisaki ◽  
Kiyoshi Sakai
Keyword(s):  
Double Bond ◽  
Side Chain

scholarly journals Effect of Fe Additives on the Catalytic Performance of Ion-Exchanged CsX Zeolites for Side-Chain Alkylation of Toluene with Methanol

Catalysts ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 829 ◽  
Author(s):  
Zhang ◽  
Yuan ◽  
Miao ◽  
Li ◽  
Shan ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Catalytic Performance ◽  
High Yield ◽  
Side Chain ◽  
Impregnation Method ◽  
Basic Sites ◽  
Lewis Acidic Sites ◽  
X Zeolite ◽  
Acidic Sites ◽  
Negative Effect

The side-chain alkylation of toluene with methanol was investigated over some Fe-modified Cs ion-exchanged X zeolite (CsX) catalysts prepared via the impregnation method using different iron sources. The absorption/activation behaviors of the reactants on the surface of the catalysts were studied by in situ Fourier-transform infrared (FT-IR) spectroscopy and temperature programmed desorption (TPD) mass measurements. Modification of CsX with a small amount of FeCl3 could result in a considerable decrease in catalytic activity, due mainly to the remarkable decrease in the density of acidic and basic sites of the catalysts. Interestingly, the Fe(NO3)3-modified CsX with an optimum Fe loading of 0.15 wt.% shows improved catalytic activity and high yield compared to the side-chain alkylation products. Modification of CsX with Fe(NO3)3 could also result in a decrease in basic sites of the catalyst. However, such a change does not bring an obvious negative effect on the adsorption/activation of toluene, while it could effectively inhibit the generation of the undesired bidentate formate. Furthermore, the introduced FeOx species (derived from the decomposition of Fe(NO3)3) may also act as new Lewis acidic sites to participate in the activation of methanol and to stabilize the formed active intermediates (i.e., unidentate formate). Therefore, modification of CsX with a suitable amount of Fe(NO3)3 may adjust its adsorption/activation ability for reagents by changing the acid–base properties of the catalyst, which can finally enhance the catalytic performance for the side-chain alkylation of toluene with methanol.

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