Diversity‐Oriented Synthesis of Morpholine‐Containing Molecular Scaffolds

Lalli, Claudia; Trabocchi, Andrea; Sladojevich, Filippo; Menchi, Gloria; Guarna, Antonio

doi:10.1002/chem.200900744

Cited by 34 publications

(18 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Owing to the instability of the putative N ‐acyl methoxy derivatives 13 and 14 , we prepared the simpler N ‐ p Tos model compound 15 , for which only one mode of cyclization55 was possible (Scheme ). The synthesis was carried out on resin 1(6) [R 1 = N ‐(2‐hydroxyethyl)].…”

Section: Resultsmentioning

confidence: 99%

Polymer‐Supported Stereoselective Synthesis of (1S,5S)‐6‐Oxa‐3,8‐diazabicyclo[3.2.1]octanes

Schütznerová¹,

Oliver²,

Zajíček³

et al. 2013

Eur J Org Chem

View full text Add to dashboard Cite

We describe a polymer‐supported stereoselective synthesis of the (1S,5S)‐6‐oxa‐3,8‐diazabicyclo[3.2.1]octane‐bridged scaffold by tandem iminium ion cyclization/nucleophilic addition reactions. A series of resin‐bound acyclic intermediates bearing different substituents were prepared, and the scope and limitations of the chemical route leading to the bridged scaffold were evaluated. The Thr‐derived bridged scaffold was found to be substantially more stable in acid than the Ser‐derived scaffold, which was partially transformed into dihydropyrazinones. Substitution at the iminium‐forming nitrogen was critical for acid stability, and the N‐arylsulfonamides with electron‐withdrawing groups yielded the highest purity of the crude products prepared by acid‐mediated cleavage. The acid‐labile target compounds were synthesized by nucleophile‐mediated cleavage from the esterified Wang resin and cyclization in formic acid.

show abstract

Section: Resultsmentioning

confidence: 99%

Polymer‐Supported Stereoselective Synthesis of (1S,5S)‐6‐Oxa‐3,8‐diazabicyclo[3.2.1]octanes

Schütznerová¹,

Oliver²,

Zajíček³

et al. 2013

Eur J Org Chem

View full text Add to dashboard Cite

show abstract

“…This intermediate revealed to be very useful for accessing diversity around the morpholine nucleus. In fact, the selection of building blocks and the choice of cyclization conditions, allowed for obtaining several skeletally different scaffolds [90]. For example, compounds 26 and 27 gave bicylic lactones 31 and 32 , respectively, upon treatment with a methanolic SOCl 2 solution.…”

Section: Case Study 3: Our Contribution To the Chemical Genetics Smentioning

confidence: 99%

Diversity-Oriented Synthesis as a Tool for Chemical Genetics

2014

Self Cite

View full text Add to dashboard Cite

Chemical genetics is an approach for identifying small molecules with the ability to induce a biological phenotype or to interact with a particular gene product, and it is an emerging tool for lead generation in drug discovery. Accordingly, there is a need for efficient and versatile synthetic processes capable of generating complex and diverse molecular libraries, and Diversity-Oriented Synthesis (DOS) of small molecules is the concept of choice to give access to new chemotypes with high chemical diversity. In this review, the combination of chemical genetics and diversity-oriented synthesis to identify new chemotypes as hit compounds in chemical biology and drug discovery is reported, giving an overview of basic concepts and selected case studies.

show abstract

“…We recently reported on the DOS of morpholine scaffolds taking advantage of a two-step process involving the combination of amino acid derivatives as building blocks, thus enabling a high degree of chemical diversity around such a heterocycle (Fig. 6) [25]. Also, the conformational analysis of peptides containing morpholine-3-carboxylic acid (Mor) suggested this molecule acts as an unexplored proline surrogate [26].…”

Section: Dos Library From Morpholine Acetalsmentioning

confidence: 99%

Chemical genetics approach to drug discovery by diversity-oriented synthesis (DOS) of peptidomimetics

Trabocchi

Cavalieri

Guarna

2011

Pure and Applied Chemistry

Self Cite

View full text Add to dashboard Cite

Chemical genetics, which relies on selecting small molecules for their ability to induce a biological phenotype or to interact with a particular gene product, is a new powerful tool for lead generation in drug discovery. Accordingly, diversity-oriented synthesis (DOS) of small-molecule peptidomimetics gives access to collections of new chemotypes bearing high structural diversity. Biological evaluation using cell growth as a phenotypic screening on Saccharomyces cerevisiae deletant strains is a powerful tool to identify new chemotypes as hit compounds in the discovery of new antifungal and anticancer agents, and also in the dissection of their mode of action. Our contribution in this field focused on the screening of morpholine-based peptidomimetic collections toward yeast deletant strains, which provided the identification of new chemotypes involved in mitochondria metabolism and respiration.

show abstract

Diversity‐Oriented Synthesis of Morpholine‐Containing Molecular Scaffolds

Cited by 34 publications

References 37 publications

Polymer‐Supported Stereoselective Synthesis of (1S,5S)‐6‐Oxa‐3,8‐diazabicyclo[3.2.1]octanes

Polymer‐Supported Stereoselective Synthesis of (1S,5S)‐6‐Oxa‐3,8‐diazabicyclo[3.2.1]octanes

Diversity-Oriented Synthesis as a Tool for Chemical Genetics

Chemical genetics approach to drug discovery by diversity-oriented synthesis (DOS) of peptidomimetics

Contact Info

Product

Resources

About