碳苷合成研究——3-β-D-吡喃木糖基-1,2,4-氧杂二唑类化合物的合成

本文研究了1-(2,3,4-三-O-苯甲酰-β-D-吡喃木糖基)-偕氨基肟与酸酐及酰氯的缩合反应,探讨了不同缩合剂、不同取代基对环合反应的影响,与酸酐反应可以一步完成,且收率较好;与酰氯反应分两步进行,第一步酰化,第二步脱水环合,芳环上取代基的电性效应,决定环合反应的难易,并证明了该环系的碳苷对酸、碱、热具有化学稳定性,本文合成了12个氧杂二唑类木糖碳苷及2个木糖基化的开环产物,通过光谱及元素分析,确定了它们的结构。     

A new route into hexahydro-cyclopenta[b]pyrrole-cis-3a,6-diols. Synthesis of constrained bicyclic analogues of pyrrolidine azasugars

Compounds that simultaneously combine charge and conformational features of glycosyltransfer transition states are of interest as transition state analog inhibitors. The synthesis of a central intermediate, cis-3a,6-dihydroxy-hexahydro-cyclopenta[b]pyrrol-2-one, which yielded a family of substituted cis-3a,6-dihydroxy-hexahydro-cyclopenta[b]pyrroles that combine conformational biasing and transition state charge mimicry, is described. The key steps in this synthesis involve synthesis of (2-azido-1,3-dihydroxy-cyclopentyl)-acetic acid ethyl ester in four steps from cyclopentenone, followed by an efficient reductive cyclization of the azide to the bicyclic lactam. The lactam was subsequently converted into the corresponding bicyclic pyrrolidine, and analogs having phenyl, hydroxyl, and phosphate substituents.     

Carbocyclic 4′-epi-formycin

Formycin is a naturally occurring biologically responsive C-nucleoside. In pursuing the design and syntheses of novel C-nucleosides, convenient access to carbocyclic C-nucleosides based on the formycin framework was a goal. One such target was carbocyclic 4′-epi-formycin (4). This compound is reported via a procedure based on an asymmetric aldol/ring closure metathesis strategy. To provide a preliminary glimpse into the biological characterization of 4 an antiviral assay was conducted. Target 4 was found to be inactive and to lack cytotoxicity to the host cells.     

伪异胞苷类化合物的合成

利用Wittig反应合成了一系列伪异胞苷类化合物,通过改进实验条件提高了关键中间体的收率,并深入研究了保护的核糖甲氧基丙烯酸乙酯与各种取代的胍和脒的缩合条件.     

Syntheses of nucleosides with a 1′,2′-β-lactam moiety as potential inhibitors of hepatitis C virus NS5B polymerase

To discover novel nucleosides as potential anti-HCV agents, nucleosides with a 1′,2′-β-lactam moiety were designed as a hybrid scaffold of MK-608 and GS-6620. Synthetic strategies were successfully developed to prepare two series of C-nucleosides with a 1′,2′-β-lactam moiety: a 7-deaza-purine C-nucleoside analog 11 was prepared in 10 steps with an overall yield of 3.7%; a purine C-nucleoside analog 22 was prepared in 9 steps with an overall yield of 9.7%.     

Construction of C-nucleosides diversified by [3+2] cycloaddition from a sugar-based mesoionic ring

A mesoionic acyclic C-nucleoside (4), serves as the starting chiron to construct highly functionalized 2-aza-7-thiabicyclo[2.2.1]heptanes and heptenes by means of a [3+2] cycloaddition with acetylenic and olefinic dipolarophiles. Further elimination of either sulfur or hydrogen sulfide leads to acyclic C-nucleosides bearing a heterocyclic moiety of 2-pyridone.     

Syntheses of 1′,2′-cyclopentyl nucleosides as potential antiviral agents

To discover novel nucleosides as potential antiviral agents, 1′,2′-cyclopentyl nucleosides were designed as hybrids of sofosbuvir and GS-6620. An asymmetric aldol condensation reaction was used as the key transformation to prepare the versatile 1′,2′-cyclopentyl ribose 6, which is useful to explore diverse bases at 1′ and its utility was demonstrated via the syntheses of nucleosides 9 and 11. The 2′-β-methyl-1′,2′-cyclopentyl ribonucleoside scaffold was exemplified via a C-nucleoside which was prepared using a RCM reaction as the key step leading to novel nucleoside 35.