Diversely C8-functionalized adenine nucleosides via their underexplored carboxaldehydes
Diversely C8-functionalized adenine nucleosides via their underexplored carboxaldehydes
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通过未充分研究的甲醛实现不同 C8 功能化的腺嘌呤核苷
DOI：
10.1039/d1cc06686b
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发表时间：
2022
影响因子：
4.9
通讯作者：
Lakshman, Mahesh K.
中科院分区：
文献类型：
--
作者：
Akula, Hari K.;Bae, Suyeal;Pradhan, Padmanava;Yang, Lijia;Zajc, Barbara;Lakshman, Mahesh K.
腺苷和 2'-脱氧腺苷的潜在多功能 N-未保护 8-甲酰基衍生物在这些核苷的 C8 修饰方面尚未得到充分利用。仅已知 8-甲酰基腺苷的原位形成，并且已经报道了 N-苯甲酰衍生物的单次应用。另一方面，8-甲酰基-2'-脱氧腺苷及其应用仍然未知。在此，我们报告了两种 N-未保护的 8-甲酰基腺嘌呤核苷衍生物的直接、可扩展的合成，并通过羟甲基化、叠氮化、CuAAC 连接、还原胺化以及使用修饰的 Julia 和 Horner-Wadsworth-Emmons 试剂进行烯化和氟烯化，证明了 C8 位的广泛多样化。
The potentially versatile N-unprotected 8-formyl derivatives of adenosine and 2′-deoxyadenosine are highly underexploited for C8 modifications of these nucleosides. Only in situ formation of 8-formyladenosine is known and a single application of an N-benzoyl derivative has been reported. On the other hand, 8-formyl-2′-deoxyadenosine and its applications remain unknown. Herein, we report straightforward, scalable syntheses of both N-unprotected 8-formyladenine nucleoside derivatives, and demonstrate broad diversification at the C8 position by hydroxymethylation, azidation, CuAAC ligation, reductive amination, as well as olefination and fluoroolefination with modified Julia and a Horner–Wadsworth–Emmons reagents.