SIMA is an analog of HEX with improved stability. 6-SIMA phosphoramidite is a fluorescent dye for oligonucleotide labeling.
Reference Reading
1. The Usefulness of Trivalent Phosphorus for the Synthesis of Dendrimers
Anne-Marie Caminade, Kathleen I Moineau-Chane Ching, Béatrice Delavaux-Nicot. Molecules. 2021 Jan 7;26(2):269. doi: 10.3390/molecules26020269.
Dendrimers are hyperbranched macromolecules, which are synthesized step-by-step by the repetition of a series of reactions. While many different types of dendrimers are known, this review focusses on the use of trivalent phosphorus derivatives (essentially phosphines and phosphoramidites) for the synthesis of dendrimers. The first part presents dendrimers constituted of phosphines at each branching point. The other parts display the use of trivalent phosphorus derivatives during the synthesis of dendrimers. Different types of reactions have been applied to phosphines. The very first examples of phosphorus-containing dendrimers were obtained by the alkylation of phosphines. Then, several families of dendrimers were elaborated by reaction of phosphoramidites. Such a type of reaction is the base of the solid phase synthesis of oligonucleotides; it has been applied in particular for the synthesis of dendrimers constituted of oligonucleotides. Finally, the Staudinger reaction between phosphines and azides afforded different families of dendrimers, and was at the origin of accelerated methods of synthesis of dendrimers. Besides, the reactivity of the P=N-P=S linkages created by this reaction led to very original dendritic structures.
2. Catalytic asymmetric and stereodivergent oligonucleotide synthesis
Aaron L Featherston, Yongseok Kwon, Matthew M Pompeo, Oliver D Engl, David K Leahy, Scott J Miller. Science. 2021 Feb 12;371(6530):702-707. doi: 10.1126/science.abf4359.
We report the catalytic stereocontrolled synthesis of dinucleotides. We have demonstrated, for the first time to our knowledge, that chiral phosphoric acid (CPA) catalysts control the formation of stereogenic phosphorous centers during phosphoramidite transfer. Unprecedented levels of diastereodivergence have also been demonstrated, enabling access to either phosphite diastereomer. Two different CPA scaffolds have proven to be essential for achieving stereodivergence: peptide-embedded phosphothreonine-derived CPAs, which reinforce and amplify the inherent substrate preference, and C2-symmetric BINOL-derived CPAs, which completely overturn this stereochemical preference. The presently reported catalytic method does not require stoichiometric activators or chiral auxiliaries and enables asymmetric catalysis with readily available phosphoramidites. The method was applied to the stereocontrolled synthesis of diastereomeric dinucleotides as well as cyclic dinucleotides, which are of broad interest in immuno-oncology as agonists of the stimulator of interferon genes (STING) pathway.
3. Improved Synthesis of Phosphoramidite-Protected N6-Methyladenosine via BOP-Mediated SNAr Reaction
Shifali Shishodia, Christopher J Schofield. Molecules. 2020 Dec 31;26(1):147. doi: 10.3390/molecules26010147.
N6-methyladenosine(m6A) is the most abundant modification in mRNA. Studies on proteins that introduce and bind m6A require the efficient synthesis of oligonucleotides containing m6A. We report an improved five-step synthesis of the m6A phosphoramidite starting from inosine, utilising a 1-H-benzotriazol-1-yloxytris(dimethylamino)phosphoniumhexafluorophosphate (BOP)-mediated SNAr reaction in the key step. The route manifests a substantial increase in overall yield compared to reported routes, and is useful for the synthesis of phosphoramidites of other adenosine derivatives, such as ethanoadenosine, an RNA analogue of the DNA adduct formed by the important anticancer drug Carmustine.
