3,4-Dideoxy-3,3,4,4-tetrafluoro- and 4-OH epimeric 3-deoxy-3,3-difluoro-α-GalCer analogues: Synthesis and biological evaluation on human iNKT cells stimulation

Abstract

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Sequential Nucleophilic Arylation/Ring-Contractive Rearrangement of N-Alkoxylactams

“…The acidic workup of the chelated intermediate C results in the generation of the N , O -hemiaminal D , which rapidly undergoes a 1,2-rearrangement through the overlap of an antibonding orbital on the C–X bond (σ* C–X ) and a bonding orbital on the C–N of the hemiaminal group (σ C–N ) to obtain α-acylpyrrolidines 6 . The α-bromo N -alkoxylactam 5 (X = Br) was used to investigate the possibility of the nucleophilic arylation/ring contraction with an organometallic reagent because the α-bromo group as a leaving group has the requisite reactivity for the ring contraction and would be tolerant in the nucleophilic addition to the amide carbonyl group without halogen–metal exchange …”

Chemical Biology of αGalCer: A Chemist's Toolbox for the Stimulation of Invariant Natural Killer T (iNKT) Cells

“…From a synthetic point of view, the most common approach for the construction of the αGalCer scaffold and the introduction of lipid modifications is strategy B (Scheme 1 and Scheme 2), allowing post-glycosylation functionalization of the acyl tail, although some examples of the use of routes A and C have been reported. [20,62,94] While conversion of commercially available phytosphingosine to azidosphingosine or other N-substituted variants (Boc, Fmoc, TCP) is an efficient direct methodology for the synthesis of analogs with different fatty acyl chains or substitutions of the amide linkage itself (e. g. triazole, ureido), it precludes the modification of the backbone length and/or its further substitution (Scheme 2A). In contrast, protocols starting with a synthetic precursor of the phytosphingosine scaffold, such as Gardner's aldehyde 26, allow for modification of the natural C18 chain by olefination, with virtually any olefination reagent.…”

Synthesis and synthetic applications of (4-hydroxyphenyl)perfluoroalkylmethanols

“…The optimized condition depicted in Entry 7 was also applicable to 7c and 7d to furnish the corresponding products 8c and 8d in excellent yields (Entries 9 and 10), respectively. Transformation of the benzylic OH group to H was usually performed by way of the Bu3SnH-mediated radical reduction of the corresponding esters [29][30][31][32] or the corresponding halide [33]. However, it is quite interesting to note that the presence of a phenolic OH group at the p-position strongly facilitated this process just by the treatment with such a convenient and safe reagent as NaBH4.…”