Synthesis of cyclic 1,3-diols as scaffolds for spatially directed libraries

Abstract

A useful design element in small molecule libraries is spatial diversity, in which binding moieties are systematically directed toward different regions of three-dimensional space. One way of achieving this is through the use of conformationally diverse scaffolds onto which various binding moieties can be placed. Such scaffolds can represent synthetic challenges of their own. In this paper, we describe a new route to chiral, cyclic 1,3-diol building blocks that features silylated dithianes as relay linchpins. These diols are subsequently used for the construction of a 24-compound pilot library bearing two amino acid residues.

Chiral-Substituted Poly-N-vinylpyrrolidinones and Bimetallic Nanoclusters in Catalytic Asymmetric Oxidation Reactions

“…The ( R )-enantiomer has a lower retention time than that of ( S )-enantiomer, which is in agreement with benzoate derivatives of ( S )- 22 and ( S )- 23 (see Supporting Information). The absolute configurations and optical purities of the unreacted diols ( R , R )- 19 –( R , R )- 21 and ( R , R )- 28 –( R , R )- 30 were similarly determined by comparison of the sign of the reported specific rotations , (Supporting Information) and through HPLC/chiral column of their dibenzoate derivatives obtained from the reactions of the diols with benzoyl chloride and pyridine (Supporting Information).…”

Early Probe and Drug Discovery in Academia: A Minireview

“…Academic early discovery programs have helped identify targets for unmet medical needs, in almost all areas of human diseases, including cancer and many metabolic, neurological, and infectious diseases. The small molecule screening decks expanded due to novel compounds and novel synthesis protocols emerging from academic synthetic chemistry research [ 39 , 40 , 41 ], or from the NIH-funded Chemical Methodologies and Library Development (CMLD) programs [ 42 , 43 , 44 ]. Several new methodologies and approaches have been reported in literature for hit evaluation [ 6 , 18 , 29 , 45 , 46 , 47 , 48 ], tapping dark matter as starting leads [ 49 ], and shifting focus to covalent binders [ 50 ].…”