Biomedical subjects
Publications and source records attributed to Junlin He.
The title compound, C10H13BrN6O3, exhibits an anti glycosylic bond conformation, with an O-C-N-C torsion angle of -105.0 (6) degrees . The pseudorotation phase angle and the amplitude [P = 5.8 (5) degrees and tau(m) = 30.0 (3) degrees , respectively] indicate N-type sugar puckering (3T2).
The synthesis of 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl nucleosides (1b, 2b, and 3b) were described and their conformation in solution as well as in the solid state was determined In addition to this, building blocks 10a,b and 13a,b were prepared and employed in solid-phase oligonucleotide synthesis. For compounds 1a and 1b the lactime proton is protected to avoid unresolved degradation of its phosphoramidites 10a,b. UV-melting studies have been carried out to assess the thermal stability of oligonucleotides containing compounds 1a,b, and 3a,b.
The 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl ortho-aza-purine and -pyrimidine nucleosides manifest an unusually rigid sugar N conformation in solution.
Oligonucleotides incorporating 8-aza-7-dazapurines (pyrazolo[3,4-d]pyrimidines) were synthesized. The corresponding nucleosides were prepared and were converted into phosphoramidites. The oligonucleotide duplex stability was studied and was compared to that of the parent compounds containing the canonical purine nucleosides. The presence of 7-halogeno or 7-alkynyl substituents increases the duplex stability significantly.
In the title compound, 2-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-1,2,4-triazine-3,5(2H,4H)-dione, C(8)H(10)FN(3)O(5), the torsion angle of the N-glycosylic bond is anti [chi = -125.37 (13) degrees]. The furanose moiety adopts the N-type sugar pucker ((3)T(2)), with P = 359.2 degrees and tau(m) = 31.4 degrees. The conformation around the C4'-C5' bond is antiperiplanar (trans), with a torsion angle gamma of 177.00 (11) degrees. A network is formed via hydrogen bonds from the nucleobases to the sugar residues, as well as through hydrogen bonds between the sugar moieties.
The nucleobase anion glycosylation of 3-bromo-4-isopropoxy-1H-pyrazolo[3,4-d]pyrimidin-6-amine (6) with 3,5-di-O-benzoyl-2-deoxy-2-fluoro-alpha-d-arabinofuranosyl bromide (5) furnished the protected N(1)-beta-d-nucleosides 7 (60%) and 8 (ca. 2%) along with the N(2)-beta-d-regioisomer 9 (9%). Debenzoylation of compounds 7 and 9 yielded the nucleosides 10 (81%) and 11 (76%). Compound 10 was transformed to the 2'-deoxyguanosine derivative 1 [6-amino-3-bromo-1-(2-deoxy-2-fluoro-beta-d-arabinofuranosyl)-1H-pyrazolo[3,4-d]pyrimidin-4-one] (85% yield) and the purine-2,6-diamine analogue 2 [3-bromo-1-(2-deoxy-2-fluoro-beta-d-arabinofuranosyl)-1H-pyrazolo[3,4-d]pyrimidin-4, 6-diamine] (78%). Both nucleosides form more than 98% N-conformer population (P(N) ca. 358 degrees and psi(m) ca. 37 degrees ) in aqueous solution. Single-crystal X-ray analysis of 1 showed that the sugar moiety displays also the N-conformation [P = 347.3 degrees and psi(m) = 34.4 degrees ] in the solid state. The remarkable rigid N-conformation of the pyrazolo[3,4-d]pyrimidine 2'-deoxy-2'-fluoro-beta-d-arabinonucleosides 1 and 2 observed in solution is different from that of the parent purine 2'-deoxy-2'-fluoro-beta-d-arabinonucleosides 3 and 4, which are in equilibrium showing almost equal distribution of the N/S-conformers.
In the title compound, C(10)H(11)BrFN(5)O(4).C(3)H(6)O.H(2)O, the N-glycosylic bond torsion angle, chi, is anti [-108.0 (4) degrees ]. The sugar pucker is N-type [C2'-exo, (2)E with P = 346.5 (4) degrees and tau(m) = 34.5 (2) degrees ], and the conformation around the C-C bond linking the CH(2) group and the furan ring is -sc [torsion angle gamma = -70.0 (4) degrees ].
Oligonucleotides incorporating the unusually linked 8-aza-7-deazapurine N8-(2'-deoxyribonucleosides) 3a,b (purine and 6-amino-2-chloropurine analogues) were used as chemical probes to investigate the base pairing motifs of the universal nucleoside 8-aza-7-deazapurin-6-amine N8-(2'-deoxyribofuranoside) 2 (adenine analogue) and that of the 2,6-diamino compound 1. Owing to the absence of an amino group on the nucleoside 3a the low stability of oligonucleotide duplexes incorporating this compound opposite to the four canonical DNA-constituents indicate hydrogen bonding and base pairing for the universal nucleosides 1 and 2 which form much more stable duplexes. When the 6-amino-2-chloro-8-aza-7-deazapurine nucleoside 3b replaces 1 and is located at the same positions, two sets of duplexes are formed (i) high Tm duplexes with 3b located opposite to dA or dC and (ii) low Tm duplexes with 3b located opposite to dG or dT. These results are due to the steric clash of the 2-chloro substituent of 3b with the 2-oxo group of dT or the 6-oxo group of dG while the 2-halogeno substituents are well accommodated in the base pairs formed with dA or dC. For comparison duplexes incorporating the regularly linked nucleosides 4-6a,b containing the same nucleobases as those of 1-3a,b were studied.
Oligonucleotides incorporating the 7-propynyl derivatives of 8-aza-7-deaza-2'-deoxyguanosine (3b) and 8-aza-7-deaza-2'-deoxyadenosine (4b) were synthesized and their duplex stability was compared with those containing the 5-propynyl derivatives of 2'-deoxycytidine (1) and 2'-deoxyuridine (2). For this purpose phosphoramidites of the 8-aza- 7-deazapurine (pyrazolo[3,4-d]pyrimidine) nucleosides were prepared and employed in solid-phase synthesis. All propynyl nucleosides exert a positive effect on the DNA duplex stability because of the increased polarizability of the nucleobase and the hydrophobic character of the propynyl group. The propynyl residues introduced into the 7-position of the 8-aza-7-deazapurines are generally more stabilizing than those at the 5-position of the pyrimidine bases. The duplex stabilization of the propynyl derivative 4b was higher than for the bromo nucleoside 4c. The extraordinary stability of duplexes containing the 7-propynyl derivative of 8-aza-7- deazapurin-2,6-diamine (5b) is attributed to the formation of a third hydrogen bond, which is apparently not present in the base pair of the purin-2,6-diamine 2'-deoxyribonucleoside with dT.
In the title regioisomeric nucleosides, alternatively called 1-(2-deoxy-beta-D-erythro-furanosyl)-1H-pyrazolo[3,4-d]pyrimidine, C(10)H(12)N(4)O(3), (II), and 2-(2-deoxy-beta-D-erythro-furanosyl)-2H-pyrazolo[3,4-d]pyrimidine, C(10)H(12)N(4)O(3), (III), the conformations of the glycosylic bonds are anti [-100.4 (2) degrees for (II) and 15.0 (2) degrees for (III)]. Both nucleosides adopt an S-type sugar pucker, which is C2'-endo-C3'-exo ((2)T(3)) for (II) and 3'-exo (between (3)E and (4)T(3)) for (III).