Synthesis of cholesteryl-α-d-lactoside via generation and trapping of a stable β-lactosyl iodide

Abstract

The generation of β-lactosyl iodide was carried out under non-in situ-anomerization, metal free conditions by reacting commercially available β-per-O-acetylated lactose with trimethylsilyl iodide (TMSI). The β-iodide was surprisingly stable as evidenced by NMR spectroscopy. Introduction of octanol or cholesterol under microwave conditions gave high yields of α-linked glycoconjugates. Careful analysis of the reaction products and mechanistic considerations suggest an acid catalyzed rearrangement that provides α-linked glycosylation products with a free C2-hydroxyl. Accessibility to these compounds may further advance glycolipidomic profiling of immune modulating bacterial derived-glycans.

Cholesterol-Based Compounds: Recent Advances in Synthesis and Applications

“…In 2015, Davis and coworkers reported the synthesis of cholesteryl-α- d -lactoside 378 via generation and trapping of stable β-lactosyl iodide 376 . The iodide derivative 376 was prepared quantitatively under non-in situ anomerization and metal-free conditions by reacting commercially available β-per- O -acetylated lactose 375 with trimethylsilyl iodide [95]. The introduction of cholesterol occurred under microwave conditions to afford the corresponding glycoconjugate 377 in 59% yield (Scheme 90).…”

“…Cholesterol glycoconjugate 377 was further deacetylated using sodium methoxide to afford cholesteryl α- d -lactoside 378 in 88% yield (Scheme 90). This glycosylation method can be employed on sterically demanding nucleophiles such as cholesterol and has potential applications in accessing structurally diverse cholesteryl glycoside analogs [95].…”