Department of Chemistry, Wayne State University , 5101 Cass Avenue, Detroit, Michigan 48202, United States.
J Am Chem Soc. 2013 Sep 25;135(38):14249-55. doi: 10.1021/ja405588x. Epub 2013 Sep 11.
The effect of a 4,6-O-alkylidene acetal on the rate of acid-catalyzed hydrolysis of methyl galactopyranosides and of spontaneous hydrolysis of 2,4-dinitrophenyl galactopyranosides has been studied through the synthesis and hydrolysis of analogs in which O6 is replaced by a methoxymethylene unit in which the methoxy group adopts either an equatorial or an axial position according to the configuration. Consistent with earlier studies under both acid-catalyzed and spontaneous hydrolysis conditions, the alkylidene acetal, or its 7-carba analog, retards hydrolysis with respect to comparable systems lacking the cyclic protecting group. The configuration at C6 in the 7-carba analogs does not influence the rate of acid-catalyzed hydrolysis but has a minor influence on the rate of spontaneous hydrolysis of the 2,4-dinitrophenyl galactosides, confirming earlier studies on the role played by the hydroxymethyl group conformation on glycoside reactivity. The benzylidene acetal is found to stabilize the α-anomer of galactopyranose derivatives relative to monocyclic analogs. Reasons for the α-selectivity of 4,6-O-benzylidene-protected galactopyranosyl donors bearing neighboring group-active protecting groups at O2 are discussed.
通过合成和水解其中 O6 被甲氧亚甲基单元取代的类似物，研究了 4,6-O-亚烷基缩醛对甲基半乳糖吡喃糖苷酸催化水解和 2,4-二硝基苯半乳糖吡喃糖苷自发水解速率的影响。根据构型，甲氧基亚甲基单元中的甲氧基采用平伏或直立位置。与酸催化和自发水解条件下的早期研究一致，亚烷基缩醛或其 7-碳类似物相对于缺乏环状保护基团的可比体系，会减缓水解速度。7-碳类似物中 C6 处的构型不会影响酸催化水解的速率，但对 2,4-二硝基苯半乳糖苷的自发水解速率有轻微影响，这证实了早期关于羟甲基构象对糖苷反应性所起作用的研究。苯亚甲基缩醛被发现相对于单环类似物稳定半乳糖吡喃糖衍生物的α-异构体。讨论了邻位基团活性保护基在 O2 上的 4,6-O-苯亚甲基保护的半乳糖基供体具有α-选择性的原因。
