1. Electrochemical Benzylic C(sp3)-H Acyloxylation
Alexander P Atkins, Albert C Rowett, David M Heard, Joseph A Tate, Alastair J J Lennox Org Lett. 2022 Jul 22;24(28):5105-5108. doi: 10.1021/acs.orglett.2c01930. Epub 2022 Jul 13.
The development of sustainable C(sp3)-H functionalization methods is of great interest to the pharmaceutical and agrochemical industries. Anodic oxidation is an efficient means of producing benzylic cations that can undergo subsequent in situ nucleophilic attack to afford functionalized benzylic products. Herein, we demonstrate the suitability of carboxylic acids as nucleophiles to yield benzylic esters. This method employs a series of secondary benzylic substrates and functionalized carboxylic acids and is demonstrated on a gram scale in flow.
2. N-carboxy-L-aspartic anhydride benzyl ester
Hitoshi Kanazawa, Jun Magoshi Acta Crystallogr C. 2003 Mar;59(Pt 3):o159-61. doi: 10.1107/s0108270103002567. Epub 2003 Feb 28.
The structure of the title compound, benzyl (1,2,3,4-tetrahydro-2,5-dioxo-1,3-oxazol-4-yl)acetate, C(12)H(11)NO(5), has been determined in an attempt to explain the polymerization observed in the solid state. The molecules are linked by intermolecular hydrogen bonds between the imino group of the five-membered ring and an adjacent carbonyl O atom, along the c axis. Intramolecular hydrogen bonds are also formed, between the imino group and the carbonyl O atom of the ester group. The five-membered rings are arranged in a layer, sandwiched by layers incorporating the benzyl groups. This structure is thought to be preferable for the polymerization of the compound in the solid state, because the five-membered rings can react with each other in the layer.
3. 1,4-Dihydropyridinebutyrolactone-derived ring-opened ester and amide analogs targeting BET bromodomains
Jiewei Jiang, Pei-Liang Zhao, Logan H Sigua, Alice Chan, Ernst Schönbrunn, Jun Qi, Gunda I Georg Arch Pharm (Weinheim). 2022 Nov;355(11):e2200288. doi: 10.1002/ardp.202200288. Epub 2022 Aug 8.
Based on a previously reported 1,4-dihydropyridinebutyrolactone virtual screening hit, nine lactone ring-opened ester and seven amide analogs were prepared. The analogs were designed to provide interactions with residues at the entrance of the ZA loop of the testis-specific bromodomain (ZA) channel to enhance the affinity and selectivity for the bromodomain and extra-terminal (BET) subfamily of bromodomains. Compound testing by AlphaScreen showed that neither the affinity nor the selectivity of the ester and lactam analogs was improved for BRD4-1 and the first bromodomain of the testis-specific bromodomain (BRDT-1). The esters retained affinity comparable to the parent compound, whereas the affinity for the amide analogs was reduced 10-fold. A representative benzyl ester analog was found to retain high selectivity for BET bromodomains as shown by a BROMOscan. X-ray analysis of the allyl ester analog in complex with BRD4-1 and BRDT-1 revealed that the ester side chain is located next to the ZA loop and solvent exposed.
