Platelet activation results in the generation of thromboxane A₂ (TxA₂), which promotes thrombus formation by further amplifying platelet function, as well as causing vasoconstriction. Due to its role in thrombus formation and cardiovascular disease, its production is the target of antiplatelet drugs such as aspirin. However, the study of TxA₂-stimulated cellular function has been limited by its instability (t_1/2 = 32 s, pH = 7.4). Although more stable analogues such as U46619 and difluorinated 10,10-F₂-TxA₂ have been prepared, we targeted a closer mimic to TxA₂ itself, monofluorinated 10-F-TxA₂, since the number of fluorine atoms can affect function. Key steps in the synthesis of F-TxA₂ included α-fluorination of a lactone bearing a β-alkoxy group, and a novel synthesis of the strained acetal. F-TxA₂ was found to be 10⁵ more stable than TxA₂, and surprisingly was only slightly less stable than F₂-TxA₂. Preliminary biological studies showed that F-TxA₂ has similar potency as TxA₂ toward inducing platelet aggregation but was superior to F₂-TxA₂ in activating integrin α_IIbβ₃.

中文翻译：

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血氧烷烷A2氟化类似物的合成，稳定性和生物学研究。

血小板活化导致血栓烷A ₂（TxA ₂）的产生，血栓烷A ₂（TxA ₂）通过进一步放大血小板功能促进血栓形成，并引起血管收缩。由于其在血栓形成和心血管疾病中的作用，其生产是抗血小板药物如阿司匹林的目标。然而，TxA ₂刺激的细胞功能的研究受到其不稳定性的限制（t _1/2 = 32 s，pH = 7.4）。尽管已经制备了更稳定的类似物，例如U46619和二氟10,10-F ₂ -TxA ₂，但我们的目标是更接近于模拟TxA ₂本身的单氟10-F-TxA ₂，因为氟原子的数目会影响功能。合成F-TxA _2的关键步骤包括带有β-烷氧基的内酯的α-氟化，以及新的应变缩醛的合成。F-为TxA ₂被发现是10 ⁵更稳定的比为TxA ₂，并且令人惊讶地是除F稳定仅略小于₂ -TxA ₂。初步生物研究表明，F-为TxA ₂具有相似的效力的Tx A ₂朝向诱导的血小板聚集，但优于到F ₂ -TxA ₂在活化整合素α _IIB β ₃。