ABSTRACT
2',3'-Cyclic canonical nucleotides are an important class of compounds playing broad roles in regulating biological processes and are investigated in the context of prebiotic chemistry as activated nucleotides for oligonucleotide formation. Despite their growing importance, synthetic access of 2',3'-cyclic nucleotides is constrained, resulting in their cost-prohibitive commercial prices. Here, we describe a microwave-assisted one-pot synthesis starting from commercially available nucleosides employing an easily available cyclophosphorylating reagent, bis(dimethyldiamino)phosphorodiamidate (BDMDAP). The corresponding 2',3'-cyclic nucleotides are isolated in good yields (70-91%) by a simple ion-exchange column with no further workup. The nucleosides require no protecting group as the cyclophosphorylation reaction is selective for the 2',3'-dihydroxyl groups. The experimental protocol is robust and can be run in parallel to provide access to gram quantities of these 2',3'-cyclic nucleotides within a day. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Procedure for the phosphorylation of nucleoside (2',3'-cyclic phosphates of nucleosides) Support Protocol: Synthesis of bis(dimethylamino)phosphorodiamidate sodium salt.
Subject(s)
Nucleosides , Phosphates , Nucleosides/chemistry , Phosphates/chemistry , Microwaves , Nucleotides/chemistry , Nucleotides, CyclicABSTRACT
Correction for 'Synthesis and hydrolytic stability of cyclic phosphatidic acids: implications for synthetic- and proto-cell studies' by Veronica Egas Ortuno et al., Chem. Commun., 2022, 58, 6231-6234, https://doi.org/10.1039/D2CC00292B.
ABSTRACT
Cyclic phosphatidic acids (cPAs) are bioactive compounds with therapuetic potential, but are in short supply. We describe a robust synthesis of cPAs employing an efficient cyclophosphorylation procedure and report on their hydrolytic properties - which should facilitate the study of their biological properties and as plausible proto- and synthetic-cell components.
Subject(s)
Phosphatidic Acids , HydrolysisABSTRACT
The prevalence of 5-hydroxydihydrofuran-2(3H)-one moiety in natural products is exploited for the first time using coronarin D, a labdane diterpene, to afford Ugi reaction product 1a and interrupted Ugi product 2a. The potential of the Ugi reaction was further extended to l-phenylalanine, 2-aminopyridine, and d-glucosamine, which afforded Ugi reaction products 3a-f, 4, and 5a-d, respectively. Cytotoxicity studies in RAW cells reveal that compounds 3e and 5b were non-toxic up to 50 µM, and these compounds were able to reduce the LPS stimulated NO production in RAW cells in par with the standard anti-inflammatory drug dexamethasone.
Subject(s)
Biological Products , Diterpenes , Diterpenes/pharmacologyABSTRACT
An approach to expand the diversity of terpenes to novel polycyclic skeletons with contiguous stereogenic centers is described. An unprecedented 8-oxabicyclo[3.2.1]octane motif was obtained in quantitative yield by photoirradiation of zerumbone in the presence of a catalytic amount of Lewis acid. The vital role of light in the isomerization of double bonds in zerumbone, which ensued cyclization via tertiary carbocation intermediate, emulates a biosynthetic route. Synthetic diversification of the phototransformed product afforded epoxy derivatives with up to seven contiguous stereogenic centers and eight-member ring fused tricyclic motifs. The present work sheds light on the possible role of UV irradiation in the biosynthesis of oxo-bridged tricyclic structures from polyene terpenes.
Subject(s)
Monocyclic Sesquiterpenes/chemistry , Sesquiterpenes/chemistry , Terpenes/chemistry , Biomimetics , Cyclization , Molecular Structure , Terpenes/isolation & purificationABSTRACT
New 1,2-dihydropyridine (1,2-DHP)-based fluorophores 1a-1h were designed and synthesized by a one-pot four-component condensation reaction using dienaminodioate, aldehydes, and an in situ-generated hydrazone mediated by trifluoroacetic acid. The photophysical properties of 1,2-DHPs were studied in detail, and a few of them exhibited selective mitochondrial staining ability in HeLa cell lines (cervical cancer cells). A detailed photophysical investigation led to the design of 1,2-DHP 1h as an optimal fluorophore suitable for its potential application as a small molecule probe in the aqueous medium. Also, 1,2-DHP 1h exhibited sixfold enhanced emission intensity than its phosphorylated analogue 1h' in the long wavelength region (λem ≈ 600 nm), which makes 1,2-DHP 1h' meet the requirement as a bioprobe for protein tyrosine phosphatases, shown in L6 muscle cell lysate.
