核苷研究2: 苄基糖核苷的立体选择性合成

1-(2, 3, 4, 6-O-四苄基吡喃糖基)-三氟乙酸酯或三氯乙酸酯在无水四氯化锡存在下与一些具有代表性的硅醚保护的碱基或者含氮杂环化合物反应, 合成了一系列新的苄基糖苷。对三氟乙酰氧基、三氯乙酰氧基作为新的离去基在核苷合成中的反应活性、立体选择性和反应收率进行了讨论。     

Regioselectivity among six secondary hydroxyl groups: selective acylation of the least reactive hydroxyl groups of inositol

We report the first, general and selective acylation of the least reactive hydroxyl group among six secondary hydroxyl groups of inositol in high yield, using very cheap and easy-to-make H(2)SO(4)-silica as the catalyst, providing easy access to bioactive molecules.     

Iodination with Silver Sulfate and Iodine. II. Uridines

Iodination of uridines with iodine and silver sulfate at room temperature gives iodinated uridines in excellent yield.     

Procedure for activating polymers with primary and/or secondary hydroxyl groups

A new facile method using 2-fluoro-1-methylpyridinium toluene-4-sulfonate (FMP) for activating polymeric hydroxyl groups has recently been developed (Refs. 1–2). Such activated polymers are useful for immobilization of enzymes, antibodies and other biomolecules and for affinity matrix development. The activation method involves reacting, at room temperature, the polymer with FMP in the presence of a tertiary amine for 0.5 to 1 hour. The activated hydroxyls react readily with nucleophiles, such as amino or thiol ligands at pH 5–10. The resulting linkages between the ligand and the polymer are respectively stable secondary amine and thioether bonds. The activated polymer remains active and usable for several months when stored at 4°C in either an acidic aqueous solution or an inert anhydrous organic solvent. The “half-life” of the activated groups in non-nucleophilic buffer solution varies from 10 to 300 hours in the pH range of 10 to 6, being most stable at low pH. Both primary and secondary hydroxyl groups of different polymers were facilely activated and shown to react readily with nucleophilic groups of biomolecules. Furthermore, FMP provides a convenient handle for the synthesis of unique conjugates consisting of FMP and a guiding molecule. These conjugates function as an activator of the hydroxyl group of a solid support as well as a molecular guide which orients the position of the ligand to be immobilized. The conjugates make it possible to immobilize ligands in an affinity-directed way.     

Iodination of phenols using chloramine T and sodium iodide

A convenient procedure for the iodination of many substituted phenols uses chloramine T and sodium iodide in DMF, DMSO, or acetonitrile.     

Reactivity of nucleosides with a hydroxyl radical in non-aqueous medium

DNA damage: The reactivity of HO(.) with silylated 2'-deoxyribonucleosides was investigated in acetonitrile by means of a time-resolved technique. The obtained rate constants were in general slightly lower than those reported for the natural nucleosides in water. Analysis of the reaction mixture by UPLC-MS revealed that HO(.) attack occurred at the nucleobase (see scheme).     

Regioselective conversion of the secondary hydroxyl groups of D-glucuronic acid without the requirement of O-protecting groups

Trifluoromethanesulfonic acid anhydride (triflic acid anhydride) transforms the bicyclic thiazolidinlactam 1 a into the crystalline elimination product 2, in which all four secondary hydroxyl groups of 1 a are differently functionalized. Compound 2 can then add nucleophiles with high chemo- and stereoselectivity. Altogether, the four secondary hydroxyl groups of D-glucuronic acid are selectively transformed without the need for any O-protecting groups. Minimizing the number of O-protecting groups is a prerequisite for the use of sugar scaffolds in molecular libraries. The hapalosin analogues 15, 16, 19, and 22 outline the strategy towards O-diversified glucose derivatives.     

Modulation of the relative reactivities of carbohydrate secondary hydroxyl groups. Modification of the hydrogen bond network

An approach towards the control of the relative regioselectivity of the secondary hydroxyl groups is presented. Original protecting groups, which are capable of specific intramolecular hydrogen bonds and are likely to modulate the partial charges of the oxygen atoms, have been developed. Qualitative NMR experiments confirmed the existence of the expected hydrogen bonds and shed light on the perturbation of the cooperative intramolecular hydrogen bond network. Further reactivity studies are presented and confirm the potential of protecting group-mediated regioselective functionalization of carbohydrates.     

Control of oxygen atom chirality and chelate ring conformation by protected/free sugar hydroxyl groups in glucose-pendant dipicolylamine-copper(II) complexes

A pair of copper(II) complexes 1 and 2 exhibit an enantiomeric chiral center at the oxygen atom that coordinates to the metal center. The configurations of the oxygen atom chirality and the chelate ring conformation are simply controlled by protected/free hydroxyl groups of the sugar moiety, yielding mirror image CD spectra. In this system, repulsive and attractive forces are used to regulate chirality on the copper-coordinated oxygen atom both in the solid state and in solution.     

Availability and disposition of hydroxyl groups on surfaces of crystalline cellulose II

The relative availabilities of hydroxyl groups at C(2), C(3), and C(6) on the D -glucopyranosyl units of a particular, highly ordered hydrocellulose II have been studied by means of the reaction of N,N-diethylaziridinium chloride, which introduces 2-(diethyl-amino)ethyl substituents. The hydrocellulose II was formed by hydrolysis of fibrous cotton cellulose II during 40 min reflux in 2.5M hydrochloric acid and is designated EHC-II (exemplar hydrocellulose II) because it represents the most highly ordered (crystalline) particles in a series of hydrocelluloses. The deviation in the distribution of substituents among the 2-O-, 3-O-, and 6-O- positions of the D -glucopyranosyl units in EHC-II from that in a disordered cellulose, in which the three types of hydroxyl groups are equally available, is the basis for estimated availabilities of the three types of hydroxyl groups on the surfaces of elementary fibrils in EHC-II. The experimental values of relative availabilities of O(2)H:O(3)H:O(6)H for EHC-II were 1.0:0.26:0.72 compared to estimated values of 1.0:0.0:.075 for surfaces of elementary fibrils of an idealized, perfectly ordered cellulose II, a model that is based on intensities of x-ray diffraction peaks.