Synthesis and conformational analysis of D-2 '-deoxy-2 ',2 '-difluoro-4 '-dihydro-4 '-thionucleosides

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	Synthesis and conformational analysis of D-2 '-deoxy-2 ',2 '-difluoro-4 '-dihydro-4 '-thionucleosides
	Zheng F(郑峰) ; Lin F(林赋) ; Wang RX(王任小) ; Qing FL(卿凤翎)
刊名	Org. Biomol. Chem.
	2010
卷号	8 期号:1 页码:163-170
ISSN号	1477-0520
其他题名	D-2-脱氧-2,2-二氟-4-二氢-4-核苷的合成和构象分析
通讯作者	卿凤翎
英文摘要	An efficient synthesis of D-2'-deoxy-2',2'-difluoro-4'-dihydro-4'-thionucleosides is described. The conformations of D-2'-deoxy-2', 2'-difluoro-4'-dihydro-4'-thiouridine were studied by X-ray crystallography, NMR spectroscopy and molecular modeling in an attempt to explore the roles of the two gem-difluorine atoms in the puckering preferences of the thiosugar ring. No matter which conformation (south or north) the thiosugar adopts, there is always one fluorine in a pseudoaxial position, with the other in a pseudoequitorial position and thus the strong antiperiplanar (ap) effects from C-H and C-C sigma-bonds to sigmaC-F are equal to each other in these two conformers. Therefore, the other weak effects, such as dipole-dipole interactions and electrostatic attractions, become more important for determining the overall conformation of the sugar ring. Based on the results of NMR spectroscopy, high-level quantum computations and molecular dynamic simulations were performed to study the preferred pucker of the thiosugar ring in solution. Our results showed that the strong antiperiplanar preference of C-H and C-C sigma-bonds to sigmaC-F and sigma*C-O seemed to be responsible for the favored S-conformation in solution, and the weak electrostatic attractions between (delta+)C2-F beta(delta-) and (delta+)H6-C6(delta-) may stabilize the preferred structure further, and keep the base moiety in a high anti-rotamer population in solution. In contrast, the packing forces (hydrogen bond OH center dot center dot center dot O=C, dipole-dipole interaction C-F center dot center dot center dot C=O) in the solid state compensated the energetic disadvantage of the relatively less stable N-conformation, and drove the thiouridine to crystallize in the N-conformation. These results, along with the earlier empirical rules regarding proton chemical shifts in carbohydrates and nucleosides, were used to propose a method based on proton chemical shifts for the analysis of the N (sic) S equilibrium of the fluorinated sugar ring.
学科主题	氟化学 ; 生命有机化学
收录类别	SCI
原文出处	http://dx.doi.org/10.1039/b914679b
语种	英语
WOS记录号	WOS:000272613300024
公开日期	2013-02-22
内容类型	期刊论文
源URL	[http://202.127.28.38/handle/331003/17693]
专题	上海有机化学研究所_中科院有机氟化学重点实验室
推荐引用方式 GB/T 7714	Zheng F,Lin F,Wang RX,et al. Synthesis and conformational analysis of D-2 '-deoxy-2 ',2 '-difluoro-4 '-dihydro-4 '-thionucleosides[J]. Org. Biomol. Chem.,2010,8(1):163-170.
APA	郑峰,林赋,王任小,&卿凤翎.(2010).Synthesis and conformational analysis of D-2 '-deoxy-2 ',2 '-difluoro-4 '-dihydro-4 '-thionucleosides.Org. Biomol. Chem.,8(1),163-170.
MLA	郑峰,et al."Synthesis and conformational analysis of D-2 '-deoxy-2 ',2 '-difluoro-4 '-dihydro-4 '-thionucleosides".Org. Biomol. Chem. 8.1(2010):163-170.