Easy Synthesis and Different Conformational Behavior of Purine and Pyrimidine .beta.-D-glycero-Pent-2'-enopyranosyl Nucleosides
Easy Synthesis and Different Conformational Behavior of Purine and Pyrimidine .beta.-D-glycero-Pent-2'-enopyranosyl Nucleosides
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嘌呤和嘧啶β-D-甘油-戊-2-烯吡喃基核苷的简单合成和不同构象行为
DOI：
10.1021/jo00129a035
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
P. Herdewijn
中科院分区：
文献类型：
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作者：
B. Doboszewski;N. Blaton;P. Herdewijn
3，4-双-O-（对-硝基苯甲酰基）-D-二甲苯醛与嘌呤和嘧啶（A，C，6-氯-嘌呤，G，T，U）在没有外加酸催化剂的情况下缩合，得到2 ′，3 ′-不饱和吡喃戊糖基核苷，收率可接受，包括α和α端基异构体，并几乎完全抑制了3 ′-取代的1 ′，2 ′-不饱和区域异构体的形成。通过~（113）C NMR确定了4 ′-O-脱保护衍生物的异头构型。在所有九个异头物对中，当与异头物的相应信号相比时，a异头物中的碳原子C-5 '的信号向高场移动。偶合常数J*# M表示嘌呤在33-40、45和46中的假轴位置。这是合理化的jt-o&r-Ns共振方面，并代表了一种情况下，糖苷类占据pseudoaxial位置通过一种机制differentthetanomeric效果。β-嘧啶30、32、42和44的相同偶联常数表明4 H 0 ** H4平衡，其中对H4形式具有边际偏好，而β-嘧啶29、31、41和43显示出对H4的偏好，这可能是由于空间相互作用。3-不饱和糖苷（伴随有1，2-不饱和区域异构体）（方案1）被称为Ferrier重排。3 - 5反应被认为是通过离域阳离子1进行的，该离域阳离子1是通过酰氧基部分从起始糖基离开，然后亲核试剂从提供最大连续轨道重叠的一侧进攻而形成的，从过渡态到产物，即导致-糖苷（方案2）。这种重叠降低了活化能，而不是导致β-糖苷的替代过渡态。(This Corey和Sneen已经提出了这样想法，以解释在酮的卤化过程中轴向产物的优先形成6，并随后用于在蔗糖的合成过程中由碘鎓离子活化的4，6-O-亚苄基-1，2，3-三脱氧-3-C-亚甲基-D-赤藓-己-1-烯吡喃糖的反应性的立体化学方面的合理化7，6-三-O-乙酰基-2-脱氧-2-亚硝基糖醛作为合成具有1，2-顺式排列的糖苷和2-氨基-2-脱氧糖苷的起始化合物。8)此外，β-糖苷可以在酸性介质中端基异构化为β-糖苷，因此有利于后者的形成，另外通过端基异构效应稳定。通常，O-、N-和
Condensation of 3, 4-bis-0-(p-nitrobenzoyl)-D-xylal with purinesand pyrimidines (A, C, 6-chloro-purine, G, T, U) without externally added acid catalyst leads to the 2', 3'-unsaturated pentopyranosyl nucleosides in preparatively acceptable yiélds of both ß and a anomers and near complete suppression of formation of the 3'-substituted l', 2'-unsaturated regioisomers. Anomeric configurations of these analogues of nucleosides have been established for the 4'-0-deprotected derivatives by way of* 113C NMR. In all nine anomeric pairs the signals of the carbon atoms C-5'in a anomers are shifted upfield when compared with the corresponding signals of the ß anomers. Coupling constants J*# M indicate pseudoaxial positions of purines in 33—40, 45, and 46. This is rationalized in terms of a jt—o&r-Ns resonance and represents a case where aglycons occupy pseudoaxial positions via a mechanism differentthan theanomeric effect. The same coupling constants of the-pyrimidines 30, 32, 42, and 44 indicate 4H0** H4 equilibrium with a marginal preference toward the H4 form, whereas the/3-pyrimidines 29, 31, 41, and 43 show a preference toward H4 probably due to steric interactions.Reaction of 1, 2-unsaturated carbohydrates or glycals2 with nucleophilic agents mediated by acids yielding 2, 3-unsaturated glycosides (accompanied by 1, 2-unsaturated regioisomers)(Scheme 1) is known as Ferrier rear-rangement. 3" 5 The reaction is believed to proceed via a delocalized cation, 1, formed by departure of the acyloxy moiety from a starting glycalfollowed by attack of nucleophile from a side which provides maximum con-tinuous overlap of orbitals in a way from transition state to product, ie, leading to-glycosides (Scheme 2). This overlap lowers the activation energy versus an alternative transition state leading to/3-glycosides.(This idea has been put forwardby Corey and Sneen in order to explain preferential formation of axial products during a halogenation of ketones6 and later used to rationalize stereochemical aspects of reactivity of 4, 6-O-benzylidene-l, 2, 3-trideoxy-3-C-methylene-D-eryi/iro-hex-l-enopyra-nose activated by iodonium ions during a synthesis of saccharose7 and also for 3, 4, 6-tri-0-acetyl-2-deoxy-2-nitroso glycals as starting compounds for syntheses of glycosides and 2-amino-2-deoxyglycosides having a 1, 2-cis arrangement. 8) Also,/3-glycosides can be anomerized to-glycosides in acidic medium, favoring therefore formation of the latter, additionally stabilized by the anomeric effect. In general,-glycosides of O-, N-, and