Efficient synthesis of polysubstituted 1,5-benzodiazepinone dipeptide mimetics via an Ugi-4CR-Ullmann condensation sequence

Synlett ◽  
2021 ◽  
Author(s):  
Robin Van Den Hauwe ◽  
Mathias Elsocht ◽  
Charlie Hollanders ◽  
Steven Ballet

An efficient three step synthesis towards 3-amino-1,4-benzodiazepin-2-one derivatives is presented. The versatile Ugi-4-component reaction (Ugi-4CR) and Boc-deprotection is followed by a ligand-free Ullmann condensation. This protocol allows the rapid construction of a diverse array of substituted 1,5-benzodiazepinones. Since Ugi-based products are typically limited by their ‘inert’ C-terminal amides, the use of a convertible (‘cleavable’) isocyanide was envisaged and resulted in building blocks that can be made SPPS-compatible. To demonstrate the potential of this novel synthetic route, the design and preparation of novel phenylurea-1,5-bezondiazepin-4(5H)-one dipeptide mimetics with potential CCK2-antagonist properties is reported.

Synthesis ◽  
2018 ◽  
Vol 50 (08) ◽  
pp. 1675-1686 ◽  
Author(s):  
Mohamed Abarbri ◽  
Badr Jismy ◽  
Hassan Allouchi ◽  
Gérald Guillaumet ◽  
Mohamed Akssira

A novel two-step synthesis of trifluoromethylated 3,5-disubstituted pyrazolo[1,5-a]pyrimidines is reported from 3-aminopyrazoles and ethyl 4,4,4-trifluorobut-2-ynoate. The synthetic route begins with the one-pot synthesis of 7-trifluoromethylated pyrazolo[1,5-a]pyrimidin-5-ones by condensation of 3-aminopyrazoles with a fluorinated alkyne. The products obtained are used as building blocks to synthesize directly, with excellent yields via C–O bond activation, a library of new fluorinated 3,5-disubstituted pyrazolo[1,5-a]pyrimidines of biological interest. This operation efficiently allows C–C, C–N and C–S bond formation.


Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3366
Author(s):  
Antonio Arcadi ◽  
Andrea Calcaterra ◽  
Giancarlo Fabrizi ◽  
Andrea Fochetti ◽  
Antonella Goggiamani ◽  
...  

An alternative Au(I)-catalyzed synthetic route to functionalized 1,2-dihydroquinolines is reported. This novel approach is based on the use of N-ethoxycarbonyl protected-N-propargylanilines as building blocks that rapidly undergo the IMHA reaction affording the 6-endo cyclization product in good to high yields. In the presence of N-ethoxycarbonyl-N-propargyl-meta-substituted anilines, the regiodivergent cyclization at the ortho-/para-position is achieved by the means of catalyst fine tuning.


ChemInform ◽  
2012 ◽  
Vol 43 (28) ◽  
pp. no-no
Author(s):  
Shafeek A. R. Mulla ◽  
Suleman M. Inamdar ◽  
Mohsinkhan Y. Pathan ◽  
Santosh S. Chavan

Author(s):  
Dominka Fedorowicz ◽  
Sylwia Banach ◽  
Patrycja Koza ◽  
Rafał Frydrych ◽  
Katarzyna Ślepokura ◽  
...  

A few suitably long dialdehyde and primary diamine building blocks of a predetermined chirality have been designed and synthesized to enable controlled and efficient synthesis of all 6 possible diastereomers...


2022 ◽  
Author(s):  
Zhi-Gang Yin ◽  
Xiong-Wei Liu ◽  
Hui-Juan Wang ◽  
Min Zhang ◽  
Xiong-Li Liu ◽  
...  

A highly efficient synthesis of structurally diverse ortho-acylphenol–diindolylmethane hybrids 3 using carboxylic acid-activated chromones as versatile synthetic building blocks is reported here for the first time, through 1,4-nucleophilic addition and followed by a decarboxylation and pyrone ring opening reaction process.


RSC Advances ◽  
2015 ◽  
Vol 5 (15) ◽  
pp. 11293-11296 ◽  
Author(s):  
Haifeng Yu ◽  
Yongmei Zhang ◽  
Tiechun Li ◽  
Peiqiu Liao ◽  
Quanping Diao ◽  
...  

An efficient synthetic route to 3-aroyl-5-formyl-4-halo pyridin-2(1H)-ones has been developed via Vilsmeier cyclization of 2-(ethylthio(arylamino)methylene)-1-alkylbutane-1,3-dione.


2021 ◽  
Author(s):  
◽  
Michael Meijlink

<p>Azasugars [e.g., 1-deoxy-aza-xylopyranose (1) Figure 1] are structural analogues of sugars [e.g., α-D-xylopyranose (2)] where the ring oxygen is substituted by a nitrogen atom. The resemblance of azasugars to their carbohydrate counterparts gives them various biological properties, such as the inhibition of glycosidase and glycosyltransferase enzymes, and as such, these compounds have been in clinical trials for the treatment of AIDS, diabetes,and cancer. Synthetic routes to azasugars have often involved the use of protecting groups, and therefore have generally reduced efficiency by requiring additional steps to apply or remove protecting groups or requiring adjustment of stereochemistry during the synthesis. This thesis presents the first example of a synthesis of four sterochemically different piperidine triols through a four-step methodology minimising the use of protecting groups starting from pentoses. The synthesis of D-xylose derived (3R,4r,5S)-piperidine triol was previously obtained in 40% yield over five steps, but was afforded in 45% overall yield over four steps using the methodology described within this thesis. Next, D-ribose derived (3R,4s,5S)-piperidine triol was obtained in 40% overall yield over four steps, which afforded a vast improvement on the previous most efficient synthetic route obtaining the azasugar in 24% yield over four steps. This four-step three-pot methodology has thus allowed for the synthesis of these piperidine triols in overall yields ranging from 4-69%, surpassing previous total syntheses in efficiency and improving overall atom economy. To further probe the applicability of the methodology, N-alkyl analogues (such as butyl-, phenylethyl-, and hydroxyethyl-analogues) of all four different piperidine triols were synthesised in comparable or greater overall yields compared to literature reports without any required adaptation to the original procedure. Included in these N-alkyl analogues are seven novel azasugars which were obtained in overall yields ranging from 6-35%.</p>


2019 ◽  
Vol 15 ◽  
pp. 811-817 ◽  
Author(s):  
Karen J Ardila-Fierro ◽  
Andrij Pich ◽  
Marc Spehr ◽  
José G Hernández ◽  
Carsten Bolm

In recent times, many biologically relevant building blocks such as amino acids, peptides, saccharides, nucleotides and nucleosides, etc. have been prepared by mechanochemical synthesis. However, mechanosynthesis of lipids by ball milling techniques has remained essentially unexplored. In this work, a multistep synthetic route to access mono- and diacylglycerol derivatives by mechanochemistry has been realized, including the synthesis of diacylglycerol-coumarin conjugates.


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