A Unified Mechanism for Abiotic Adenine and Purine Synthesis in Formamide
A Unified Mechanism for Abiotic Adenine and Purine Synthesis in Formamide
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DOI：
10.1002/anie.201108907
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发表时间：
2012-01-01
影响因子：
16.6
通讯作者：
Springsteen, Greg
中科院分区：
文献类型：
--
作者：
Hudson, Jeremy S.;Eberle, Joseph F.;Springsteen, Greg
通过甲酰胺脱水缩合合成嘌呤是一种潜在的非生物核碱基来源。自20世纪50年代以来，有报道称将甲酰胺加热至接近沸点可高产出嘌呤（> 70%）这种甲酰胺缩合的范围已经扩大了多种生物相关产品的鉴定，包括核碱基和氨基酸衍生物，从纯和矿物掺杂的甲酰胺。[2-4]已经提出了嘌呤的机制途径，[3-8]尽管导致相关产物的途径之间存在显着差异。在此，数据提出了一个共同途径的非生物合成嘌呤和腺嘌呤从甲酰胺；所提出的途径也非常类似于嘌呤核碱基的生物合成（方案1）。这是第一个表明甘氨酸衍生物是甲酰胺合成嘌呤的关键中间体的证据，并且这个甘氨酸主链在与嘌呤环生物合成相同的方向上形成了嘌呤环生产的支架。核碱基生物合成和非生物合成之间的相似之处可能暗示了这种代谢途径的起源。[9]非生物核碱基及其类似物已在陨石、[10]火花放电实验、[11]和氰化氢缩合反应中被发现。[12-15]典型的实验室程序要求在25 - 708℃的氨水中加入1 - 15m HCN。[12-14] Oró、Orgel和Ferris对HCN到腺嘌呤的非光化学机制途径进行了分析。[12-15]简而言之，二氨基马来腈（DAMN）是一种相对稳定的HCN四聚体，已被确定为重要的中间体。通过与氰化物衍生的甲脒反应，它提供随后与咪唑和双环嘌呤闭合的环结支架（方案2）。在水
The synthesis of purines through dehydration and condensation of formamide is a potential abiotic source of nucleobases. It has been reported since the 1950s that heating formamide to near boiling generates purine in high yield (> 70%).[1] The scope of this formamide condensation has been broadened by the identification of multiple biologically relevant products, including nucleobases and amino acid derivatives, from both neat and mineral-doped formamide.[2–4] Mechanistic pathways to purines have been proposed,[3–8] though there are significant variations between routes leading to related products. Herein, data is presented suggesting a common pathway for the abiotic syntheses of both purine and adenine from formamide; the proposed route is also highly reminiscent of the biosynthesis of purine nucleobases (Scheme 1). This is the first evidence suggesting that a glycine derivative is a critical intermediate in purine synthesis from formamide, and that this glycine backbone forms a scaffold for purine ring production in the same orientation as in purine ring biosynthesis. Parallels between nucleobase biosynthesis and plausible abiotic syntheses may allude to the origins of this metabolic pathway.[9]Abiotic nucleobases and their analogues have been identified in meteorites,[10] spark discharge experiments,[11] and hydrogen cyanide (HCN) condensation reactions.[12–15] Typical laboratory procedures call for one to 15m HCN in aqueous ammonia at 25–708C.[12–14] Analyses of the nonphotochemical, mechanistic route from HCN to adenine have been conducted by Oró, Orgel, and Ferris.[12–15] Briefly, diaminomaleonitrile (DAMN), a relatively stable HCN tetramer, has been identified as an important intermediate. It provides the ring junction scaffold that subsequently closes to an imidazole and then a bicyclic purine, through reaction with cyanide-derived formamidine (Scheme 2). In aqueous