Fig. 2: Synthesis of the monosaccharide and oligosaccharide building blocks.
From: Comprehensive synthesis and anticoagulant evaluation of a diverse fucoidan library
a Synthesis of monosaccharides 59-63. b Synthesis of disaccharides 64, 65, and 67. c Synthesis of disaccharide acceptors 69 and 71. d Synthesis of tetrasaccharides 72 and 73. e Synthesis of tetrasaccharides 74, 75, and 77. Reagents and conditions: (1) (a) Ac2O, HClO4, 0 °C, 1 h; (b) p-TolSH, BF3-OEt2, DCM, 0 °C to rt; (c) NaOCH3, CH3OH, rt, 1 h; (d) PhC(OCH3)3, CSA, MeCN, rt, 3 h; (e) BnBr, NaH, DMF, 0 °C, 3 h; (f) 1 N HCl, rt, 1 h; (2) TBSCl, imidazole, DMF, 70 °C, 4 h; (3) (a) CH3OH, 4 Å MS, p-TolSCl, AgOTf, TTBP, DCM,− 78 °C, 1 h; (b) HF-pyridine, THF, 50 °C, 4 h; (4) (a) NaOCH3, CH3OH, 50 °C, 1 h; (b) Bu2SnO, toluene, 120 °C, 6 h; (c) PMBCl, CsF, DMF, 70 °C, 4 h; (5) TTBP, 4 Å MS, DCM, p-TolSCl, AgOTf, then 59, − 78 °C to rt, 1.5 h; (6) HF-pyridine, THF, 50 °C, 4 h; (7) TTBP, 4 Å MS, DCM, p-TolSCl, AgOTf, then 61, − 78 °C to rt, 1.5 h; (8) TTBP, 4 Å MS, DCM, p-TolSCl, AgOTf, then 62, − 72 °C to rt, 1.5 h; (9) HF-pyridine, THF, 45 °C, 6 h; (10) TTBP, 4 Å MS, DCM, p-TolSCl, AgOTf, then 63, − 72 °C to rt, 1.5 h; (11) TTBP, 4 Å MS, DCM, p-TolSCl, AgOTf, then 59, − 78 °C to rt, 1.5 h; (12) p-TolSCl, AgOTf, then 59, − 78 °C to rt, 1.5 h; (13) TTBP, 4 Å MS, DCM, p-TolSCl, AgOTf, then 62, − 72 °C to rt, 1.5 h; (14) p-TolSCl, AgOTf, then 59, − 72 °C to rt, 1.5 h; (15) p-TolSCl, AgOTf, then 62 or 63, − 72 °C to rt, 1.5 h. Tol, p-methylphenyl; Bz, benzoyl; Bn, benzyl; TBS, tert-butyldimethylsilyl; PMB, p-methoxybenzyl; TTBP, 2,4,6-tri-tert-butylpyrimidine; MS, molecular sieves.
