Temporary Protection and Activation in the Regioselective Synthesis of Saccharide Sulfates

Regioselective sulfation with Et₃N · SO₃ of partially protected or unprotected glycosides via stannanediyl acetals or stannyl ethers, combined with persistent or temporary protecting groups is described. Stannylation of phenylboronates, followed by sulfation and aqueous workup, is an efficient way for the synthesis of monosulfated monosaccharides. The stannanediyl acetal 2 led in high yields to 3a , while sulfation of the diol 1 proceeded more slowly and led in lower yield to a mixture 1/3a/4a/5a (Scheme 1). The trehalose disulfate 8a was obtained in high yields from 7 ; reducing the amount of sulfating agent led to a mixture 6/8a/9a . Stannylation and sulfation of the galactoside 11 afforded 13a , while direct sulfation of 11 gave a mixture of the 2-and 3-sulfates 13a/14a besides some disulfate 15a . Sulfation of the lactose derivative 16 and the stannanediyl acetal 17 gave the 3-sulfate 18a , with some disulfate 19a being formed from 16 . The mannopyranoside 21 was selectively sulfated at OH–C(2), leading to 22a , while the corresponding diol 20 yielded mostly the isomer 23a and some disulfate 24a . Sulfation of the stannyl ethers derived from the gluco-and galactopyranosides 25 and 28 and (Bu₃Sn)₂O afforded high yields of the 2,6-disulfate 26a and the 3,6-disulfate 29a , respectively. Stannylation of 25 and 28 with Bu₂SnO and sulfation proceeded less satisfactorily. Stannylation of the phenylboronate 32 (Bu₂SnO) and sulfation gave good yields of the 2-sulfate 27a ; stannylation and benzoylation yielded the 2-benzoate 34 (Scheme 2). Similarly, the galactose-derived 37 provided high yields of the 3-sulfate 30a and of the 3-benzoate 39 . Direct sulfation of the phenylboronates 32 and 37 proceeded in lower yields and gave mixtures.