113890-38-3Relevant articles and documents
Prebiotic phosphorylation of 2-thiouridine provides either nucleotides or DNA building blocks via photoreduction
Xu, Jianfeng,Green, Nicholas J.,Gibard, Clémentine,Krishnamurthy, Ramanarayanan,Sutherland, John D.
, p. 457 - 462 (2019/04/08)
Breakthroughs in the study of the origin of life have demonstrated how some of the building blocks essential to biology could have been formed under various primordial scenarios, and could therefore have contributed to the chemical evolution of life. Missing building blocks are then sometimes inferred to be products of primitive biosynthesis, which can stretch the limits of plausibility. Here, we demonstrate the synthesis of 2′-deoxy-2-thiouridine, and subsequently 2′-deoxyadenosine and 2-deoxyribose, under prebiotic conditions. 2′-Deoxy-2-thiouridine is produced by photoreduction of 2,2′-anhydro-2-thiouridine, which is in turn formed by phosphorylation of 2-thiouridine—an intermediate of prebiotic RNA synthesis. 2′-Deoxy-2-thiouridine is an effective deoxyribosylating agent and may have functioned as such in either abiotic or proto-enzyme-catalysed pathways to DNA, as demonstrated by its conversion to 2′-deoxyadenosine by reaction with adenine, and 2-deoxyribose by hydrolysis. An alternative prebiotic phosphorylation of 2-thiouridine leads to the formation of its 5′-phosphate, showing that hypotheses in which 2-thiouridine was a key component of early RNA sequences are within the bounds of synthetic credibility.
A 2-deoxy-D-ribose preparation method
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Paragraph 0067; 0076; 0077, (2019/02/02)
The invention discloses a preparation method of 2-deoxidation-D-ribose. The method comprises the following steps: (1) carrying out a Reformasky reaction on D-glyceraldehyde acetonide and ethyl bromoacetate at an inert atmosphere and under a catalytic action of active zinc powder so as to obtain a compound shown in the formula I; (2) carrying out a substitution reaction on the compound shown in the formula I and an organic silicon protecting agent in the presence of an alkali so as to obtain a compound shown in the formula II; (3) carrying out a reduction reaction on the compound shown in the formula II under the condition of a reducing agent so as to obtain a compound shown in the formula III; (4) carrying out an oxidation reaction on the compound shown in the formula III under the condition of an oxidizing agent so as to obtain a compound shown in the formula IV; (5) carrying out deprotection on the compound shown in the formula IV in the presence of an acid and then carrying out a cyclization reaction so as to obtain the 2-deoxidation-D-ribose. According to the method, the Reformasky reaction is adopted, so that the selectivity is good; the high-yield compound shown in the formula I is obtained. The method is convenient to operate, low in raw material cost and easy to industrialize.
Transition state analysis of thymidine hydrolysis by human thymidine phosphorylase
Schwartz, Phillip A.,Vetticatt, Mathew J.,Schramm, Vern L.
supporting information; experimental part, p. 13425 - 13433 (2010/12/19)
Human thymidine phosphorylase (hTP) is responsible for thymidine (dT) homeostasis, and its action promotes angiogenesis. In the absence of phosphate, hTP catalyzes a slow hydrolytic depyrimidination of dT yielding thymine and 2-deoxyribose (dRib). Its transition state was characterized using multiple kinetic isotope effect (KIE) measurements. Isotopically enriched thymidines were synthesized enzymatically from glucose or (deoxy)ribose, and intrinsic KIEs were used to interpret the transition state structure. KIEs from [1′- 14C]-, [1-15N]-, [1′-3H]-, [2′R-3H]-, [2′S-3H]-, [4′- 3H]-, and [5′-3H]dTs provided values of 1.033 ± 0.002, 1.004 ± 0.002, 1.325 ± 0.003, 1.101 ± 0.004, 1.087 ± 0.005, 1.040 ± 0.003, and 1.033 ± 0.003, respectively. Transition state analysis revealed a stepwise mechanism with a 2-deoxyribocation formed early and a higher energetic barrier for nucleophilic attack of a water molecule on the high energy intermediate. An equilibrium exists between the deoxyribocation and reactants prior to the irreversible nucleophilic attack by water. The results establish activation of the thymine leaving group without requirement for phosphate. A transition state constrained to match the intrinsic KIEs was found using density functional theory. An active site histidine (His116) is implicated as the catalytic base for activation of the water nucleophile at the rate-limiting transition state. The distance between the water nucleophile and the anomeric carbon (rC-O) is predicted to be 2.3 A at the transition state. The transition state model predicts that deoxyribose adopts a mild 3′-endo conformation during nucleophilic capture. These results differ from the concerted bimolecular mechanism reported for the arsenolytic reaction (Birck, M. R.; Schramm, V. L. J. Am. Chem. Soc. 2004, 126, 2447-2453).
