本研究主要針對開發新的合成方法來進行S-亞硝基硫醇 (RSNOs) 的共軛反應，並對其產物進行衍生化合成。我們利用RSNO和重氮甲基膦酸二甲酯 (dimethyl (diazomethyl)phosphonate，DAMP) 進行增碳反應得到硫氰酸酯與異硫氰酸酯化合物。該反應涉及S-亞硝基硫醇與去質子化的重氮甲基膦酸二甲酯反應形成親和性加成產物，經歷脫除二甲基膦酸鉀得到熱不穩定的重氮烯，再脫去氮氣以進行亞烷基卡賓的重排反應形成穩定的產物。
在過往文獻中，大多數皆使用強鹼 (t-BuOK) 搭配極低溫 (-78 ℃)的環境將重氮甲基膦酸二甲酯去質子化，形成具有親核性的α- 碳負離子。為使共軛反應能在較溫和的條件下進行，在此我們也設計一個不同於以往的反應路徑，使用較溫和的1,8-二氮雜二環[5.4.0]十一碳-7-烯 (DBU) 來活化重氮甲基膦酸二甲酯形成DAMP陰離子。再利用DAMP陰離子與S-亞硝基硫醇進行親核性加成反應，形成硫氰酸酯與異硫氰酸酯化合物。其中一、二級的S-硝基硫醇將得到硫氰酸酯，而三級的S-硝基硫醇會形成異硫氰酸酯化合物，因此經由我們的共軛反應可以區分出一、二級與三級化合物。後續將得到的產物分別進行衍生化反應形成螢光分子以利於監測，期能用於設計S-亞硝化蛋白質的新型生物傳感器。
另外，S-亞硝基硫醇具有許多生物學意義，但很少用於有機合成。在本研究中，該方法的獨特性是最終產物上不具有共軛膦試劑的殘留，因此能有效地將相應硫醇的RSNO轉化為硫氰酸酯或異硫氰酸酯化合物，為RSNO的有機合成提供了新的方法。

A novel ligation of S-nitrosothiols (RSNOs) and the subsequent derivatization were developed in this research. RSNOs underwent a homologation process to afford thiocyanate or isothiocyanate compounds with dimethyl (diazomethyl)phosphonate (DAMP).
Differentiated from the previous literatures that strong bases (t-BuOK or n-BuLi) were selected for the deprotonation of alkenyl proton at low temperature (-78 ℃), an DAMP anion was generated through an induced-deprotonation of dimethyl (diazomethyl)- phosphonate with a mild base 1,8-Diazabicyclo(5.4.0)undec-7-ene (DBU). The in situ carbanion of DAMP participated in the nucleophilic addition onto the electron-deficient RSNO to form a Wittig-type intermediate and rearranged into the final product accompanying with a loss of one molecular of nitrogen gas. Primary, secondary and tertiary S-nitrosothiols can be distinguished in our ligation strategy. The primary and secondary RSNOs gave thiocyanates as, while the tertiary RSNOs afforded corresponding isothiocyanates. Subsequent reactions converted products into fluorescent molecules which could be used as new biosensors of S-nitrosated proteins observation.
Furthermore, S-nitrosothiols have a great number of biological activities, but are rarely used in organic syntheses. This research also provided a practical traceless ligation method of SNO without any phosphine reagent or phosphonate group left and a new method for the organic syntheses of thiocyanates or isothiocyanates from S-nitrosothiols.

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