Synthetic Chemical Probes That Dissect Vitamin D Activities

Abstract

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Design and Synthesis of Fluoro Analogues of Vitamin D

“…As mentioned in Section 2.1 , Uesugi and colleagues reported the first synthesis of 3-fluoro-19-norVD 3 analogues and evaluated their SREBP inhibitory activity vs. VDR activity (see Scheme 8 ) [ 29 ].…”

“…In 2019, Uesugi and colleagues published the first synthesis of 1-fluoro-19-norVD 3 analogues [29]. They constructed 1-hydroxy-19-norvitamin D 3 structures with a modified Julia olefination method [30], and the direct deoxyfluorination of C1 yielded the corresponding 1-fluorinated analogues (22,23).…”

“…In this reaction sequence, shown in Scheme 8, they also obtained 3-fluoro-19-norVD 3 analogues (24,25). Some of these analogues were poor VDR binders but showed potent sterol regulatory element-binding protein (SREBP) inhibitory activity via inducing SREBP cleavage-activating protein (SCAP) degradation [29]. In 2019, Uesugi and colleagues published the first synthesis of 1-fluoro-19-norVD3 analogues [29].…”

“…Some of these analogues were poor VDR binders but showed potent sterol regulatory element-binding protein (SREBP) inhibitory activity via inducing SREBP cleavage-activating protein (SCAP) degradation [29]. In 2019, Uesugi and colleagues published the first synthesis of 1-fluoro-19-norVD3 analogues [29]. They constructed 1-hydroxy-19-norvitamin D3 structures with a modified Julia olefination method [30], and the direct deoxyfluorination of C1 yielded the corresponding 1-fluorinated analogues (22,23).…”

“…Next, 2α-fluorovitamin D 3 (27) was also synthesized, and its biological activity was tested in 1986 [32]. Electrophilic 2α-fluorination of 3,6β-diacetoxycholest-2-ene (28) using CsSO 4 F gave 2α-fluoroketone (29). To construct the B-secosteroidal structure, conventional photochemical conversion and subsequent thermal isomerization were applied (Scheme 10) [32].…”