TY - JOUR
T1 - Regioselective silyl/acetate exchange of disaccharides yields advanced glycosyl donor and acceptor precursors
AU - Hsieh, Hsiao Wu
AU - Schombs, Matthew W.
AU - Witschi, Mark A.
AU - Gervay-Hague, Jacquelyn
PY - 2013/10/4
Y1 - 2013/10/4
N2 - Glycoconjugates are composed of carbohydrate building blocks linked together in a multitude of ways giving rise to diverse biological functions. Carbohydrates are especially difficult to synthetically manipulate because of the similar reactivity of their numerous and largely equivalent hydroxyl groups. Hence, methodologies for both the efficient protection and selective modification of carbohydrate alcohols are considered important synthetic tools in organic chemistry. When per-O-TMS protected mono- or disaccharides in a mixture of pyridine and acetic anhydride are treated with acetic acid, regioselective exchange of silicon for acetate protecting groups occurs. Acid concentration, thermal conditions, and microwave assistance mediate the silyl/acetate exchange reaction. Regiocontrol is achieved by limiting the equivalents of acetic acid, and microwave irradiation hastens the process. We coined the term Regioselective Silyl Exchange Technology (ReSET) to describe this process, which essentially sets the protecting groups anew. To demonstrate the scope of the reaction, the conditions were applied to lactose, melibiose, cellobiose, and trehalose. ReSET provided rapid access to a wide range of orthogonally protected disaccharides that would otherwise require multiple synthetic steps to acquire. The resulting bifunctional molecules are poised to serve as modular building blocks for more complex glycoconjugates.
AB - Glycoconjugates are composed of carbohydrate building blocks linked together in a multitude of ways giving rise to diverse biological functions. Carbohydrates are especially difficult to synthetically manipulate because of the similar reactivity of their numerous and largely equivalent hydroxyl groups. Hence, methodologies for both the efficient protection and selective modification of carbohydrate alcohols are considered important synthetic tools in organic chemistry. When per-O-TMS protected mono- or disaccharides in a mixture of pyridine and acetic anhydride are treated with acetic acid, regioselective exchange of silicon for acetate protecting groups occurs. Acid concentration, thermal conditions, and microwave assistance mediate the silyl/acetate exchange reaction. Regiocontrol is achieved by limiting the equivalents of acetic acid, and microwave irradiation hastens the process. We coined the term Regioselective Silyl Exchange Technology (ReSET) to describe this process, which essentially sets the protecting groups anew. To demonstrate the scope of the reaction, the conditions were applied to lactose, melibiose, cellobiose, and trehalose. ReSET provided rapid access to a wide range of orthogonally protected disaccharides that would otherwise require multiple synthetic steps to acquire. The resulting bifunctional molecules are poised to serve as modular building blocks for more complex glycoconjugates.
UR - http://www.scopus.com/inward/record.url?scp=84885163649&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885163649&partnerID=8YFLogxK
U2 - 10.1021/jo4013805
DO - 10.1021/jo4013805
M3 - Article
C2 - 23980653
AN - SCOPUS:84885163649
VL - 78
SP - 9677
EP - 9688
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
SN - 0022-3263
IS - 19
ER -