51549-40-7Relevant articles and documents
223. Phosphoramidites of Chiral (RP)- and (SP)-Configurated d(T-A): Synthesis, Configurational Assignment, and Use as Dimer Blocks in Oligonucleotide Synthesis
Herdering, Wilhelm,Kehne, Andreas,Seela, Frank
, p. 2119 - 2127 (1985)
The N,N-diisopropylphosphoramidites 10a and 10b of appropriately protected chiral diastereoisomers of d(T>P-18O>-A) (8a and 8b, resp.), chiral by virtue of the isotope 18O at the P-atom, have been synthesized.The 18O-isotope was incorporated by oxidation of the phosphite triester 3 with H2/I2.Separation of the diastereoisomers was accomplished by flash chromatography of the O-3'-deprotected phosphate triesters 5a/b.The absolute configuration at the chiral P-atom was deduced from the methylation products of the fully deprotected diastereoisomers 8a and 8b.Phosphinylation of 5a and 5b yielded the configurationally pure phosphoramidites 10a and 10b, respectively, which were then employed in solid-phase synthesis to yield the self-complementary oligomers d(G-A-G-T-(RP)--A-C-T-C) (13) and d(G-A-G-T-(SP)--A-C-T-C) (14), respectively.
Enantiodivergent Formation of C-P Bonds: Synthesis of P-Chiral Phosphines and Methylphosphonate Oligonucleotides
Baran, Phil S.,Eastgate, Martin D.,Knouse, Kyle W.,Padial, Natalia M.,Rivas-Bascón, Nazaret,Schmidt, Michael A.,Vantourout, Julien C.,Xu, Dongmin,Zheng, Bin
, (2020/03/30)
Phosphorus Incorporation (PI, abbreviated Π) reagents for the modular, scalable, and stereospecific synthesis of chiral phosphines and methylphosphonate nucleotides are reported. Synthesized from trans-limonene oxide, this reagent class displays an unexpected reactivity profile and enables access to chemical space distinct from that of the Phosphorus-Sulfur Incorporation reagents previously disclosed. Here, the adaptable phosphorus(V) scaffold enables sequential addition of carbon nucleophiles to produce a variety of enantiopure C-P building blocks. Addition of three carbon nucleophiles to Π, followed by stereospecific reduction, affords useful P-chiral phosphines; introduction instead of a single methyl group reveals the first stereospecific synthesis of methylphosphonate oligonucleotide precursors. While both Π enantiomers are available, only one isomer is required - the order of nucleophile addition controls the absolute stereochemistry of the final product through a unique enantiodivergent design.
C5′-adenosinyl radical cyclization. A stereochemical investigation
Navacchia, Maria Luisa,Chatsilialoglu, Chryssostomos,Montevecchi, Pier Carlo
, p. 4445 - 4452 (2007/10/03)
A variety of substituted 2′-deoxyadenosin-5′-yl radicals 3 were generated under different reaction conditions. Radicals 3 underwent intramolecular cyclization onto the C8-N7 double bond of the adenine moiety leading to aminyl radicals (5′S,8R)-4 and (5′R,8R)-4 and, eventually, to the corresponding cyclonucleosides 5 and 6. The effect of the solvent, the nature of the substituents, and the generation method of radicals 3 on the stereoselectivity of the C5′-radical cyclization have been considered. The observed increase of the (5′S)/(5′R) ratio by increasing the bulkiness of the R1 group is explained in terms of steric repulsion between R1 and the purine moiety which favors the C5′-endo conformation, whereas the effect of the water solvent in promoting the (5′R)-stereoselective cyclization is ascribed to intermolecular hydrogen bonding stabilizing the C5′-exo confomation.
