Nolen Ernest G, Hornik Ezra S, Jeans Kendra B, Zhong Weiyu, LaPaglia Danielle M
Department of Chemistry, Colgate University, 13 Oak Drive, Hamilton, NY 13346, USA.
Tetrahedron Lett. 2021 Jun 8;73. doi: 10.1016/j.tetlet.2021.153109. Epub 2021 Apr 23.
Inspired by reports of water sculpted Tn antigen (α-GalNAc--Ser/Thr) epitopes and our interest in producing metabolically more stable -linked analogs of Tn, we explored the utility of C2 functionality on α-Gal--alkenes to deliver hydroxyl to the pendant alkenyl chain. Toward this end, a cyclic carbonate approach gave rise to a single -linked α-Gal-1'(S)-hydroxyethane in 3 steps, and use of a 2-(hydroxyimino)galactoside cyclization transferred an oxygen to a pendant -substituted -linked alkene affording the -configuration at the newly formed stereocenter (7:1 dr). Reduction and acetylation of the resultant isoxazoline demonstrated this approach as a viable route to -linked α-GalNAc-1'-hydroxyalkanes.
受水雕刻的Tn抗原（α-GalNAc--Ser/Thr）表位报道的启发，以及我们对生产代谢更稳定的Tn的β-连接类似物的兴趣，我们探索了α-Gal-烯烃上C2官能团用于向侧链烯基链提供羟基的效用。为此，一种环状碳酸酯方法通过3步反应得到了单一的β-连接的α-Gal-1'（S）-羟基乙烷，并且使用2-（羟基亚氨基）半乳糖苷环化将一个氧转移到侧链β-取代的β-连接烯烃上，在新形成的立体中心得到β-构型（7:1的非对映体比例）。所得异恶唑啉的还原和乙酰化证明了这种方法是通往β-连接的α-GalNAc-1'-羟基烷烃的可行途径。
