Synthesis of an allergy inducing tetrasaccharide “4P-X”

Synthesis of 6′-galactosyllactose, a deviant human milk oligosaccharide, with the aid of Candida antarctica lipase-B

“…1 H NMR (400 MHz, CDCl 3 ) δ 6.14 (d, J = 3.6 Hz, 1H, H-1), L-Fucose (9). Prepared according to general procedure with 8 in 10 days gave white solid, yield 12 mg (24%); NMR matches with the commercial one.…”

“…Prepared according to general procedure with 11 in 48 h gave white solid, yield 59 mg (63%); TLC – PE : EtOAc 1 : 2, R f = 0.29; mp 91–93 °C (from DCM); [ α ] 20 D +45.0 (CH 2 Cl 2 , c 0.10); 1 H NMR (400 MHz, CDCl 3 ) δ 6.26 (d, J = 3.7 Hz, 1H, H-1), 5.47 (t, J = 9.8 Hz, 1H, H-3), 5.35 (dd, J = 0.8, 3.4 Hz, 1H, H′-4), 5.12 (dd, J = 7.9, 10.4 Hz, 1H, H′-2), 5.00 (dd, J = 3.4, 10.4 Hz, 1H, H′-3), 4.96 (dd, J = 3.7, 10.3 Hz, 1H, H-2), 4.62 (d, J = 7.9 Hz, 1H, H′-1), 4.14 (dd, J = 6.5, 11.1 Hz, 1H, H′-6a/6b), 4.08 (dd, J = 7.1, 11.1 Hz, 1H, H′-6a/6b), 3.97 (t, J = 9.7 Hz, 1H, H-4), 3.91 (t, J = 6.8 Hz, 1H, H′-5), 3.71–3.88 (m, 3H, H-5,6a,6b), 2.16 (s, 3H), 2.15 (s, 3H), 2.05 (s, 3H), 2.05 (s, 6H), 2.01 (s, 3H), 1.96 (s, 3H), 1.93 (dd, J = 4.3, 9.4 Hz, 1H, OH-6); 13 C NMR (101 MHz, CDCl 3 ) δ 170.5, 170.3, 170.2, 170.1, 169.9, 169.3, 169.3, 101.2 (C′-1), 89.3 (C-1), 74.6 (C-4), 73.1 (C-5), 71.1 (C′-3), 70.8 (C′-5), 69.8 (C-3), 69.7 (C-2), 69.4 (C′-2), 66.9 (C′-4), 61.0 (C′-6), 60.0 (C-6), 21.1, 21.0, 20.9, 20.8, 20.7; HRMS (AJS-ESI): calculated for C 26 H 36 O 18 Na [M + Na] + 659.1794, found 659.1784; NMR matches with literature data. 9…”

“…1,2-Di-O-acetyl-6-deoxy-L-galactopyranoside (10). Prepared according to general procedure with 8 in 10 days gave slightly yellowish white solid, α : β 61 : 39; yield 12 mg (16%); TLC -PE : EtOAc 1 : 2, R f = 0.15; mp 105-107 °C (from DCM); NMR data for α-anomer: 1 H NMR (400 MHz, CDCl 3 ) δ 6.25 (d, J = 3.8 Hz, 1H, H-1), 5.15 (dd, J = 3.8, 10.3 Hz, 1H, H-2), 4.11 (q, J = 6.6 Hz, 1H, H-5), 4.00 (dd, J = 3.3, 10.2 Hz, 1H, H-3), 3.87 (d, J = 2.6 Hz, 1H, H-4), 2.12 (s, 3H), 2.08 (s, 3H), 1.31 (d, J = 6.6 Hz, 3H, CH 3 ); 13 NMR data for β-anomer: 1 H NMR (400 MHz, CDCl 3 ) δ 5.60 (d, J = 8.3 Hz, 1H, H-1), 5.04 (dd, J = 8.4, 9.6 Hz, 1H, H-2), 3.75-3.82 (m, 2H, H-4,5), 3.71 (dd, J = 3.4, 9.7 Hz, 1H, H-3), 2.11 (s, 3H), 2.10 (s, 3H), 1.36 (d, J = 6.5 Hz, 1H, CH 3 ); 13 (dd, J = 0.8, 3.4 Hz, 1H, H′-4), 5.12 (dd, J = 7.9, 10.4 Hz, 1H, H′-2), 5.00 (dd, J = 3.4, 10.4 Hz, 1H, H′-3), 4.96 (dd, J = 3.7, 10.3 Hz, 1H, H-2), 4.62 (d, J = 7.9 Hz, 1H, H′-1), 4.14 (dd, J = 6.5, 11.1 Hz, 1H, H′-6a/6b), 4.08 (dd, J = 7.1, 11.1 Hz, 1H, H′-6a/6b), 3.97 (t, J = 9.7 Hz, 1H, H-4), 3.91 (t, J = 6.8 Hz, 1H, H′-5), 9 Phenyl 2,3-di-O-acetyl-1-thio-β-D-glucopyranoside (14). Prepared according to general procedure with 13 in 3 days gave white solid, yield 69 mg (85%); with N435 (200 mg) and reflux in 2 h gave white solid, yield 74 mg (91%); TLC -PE : EtOAc 1 : 1, R f = 0.12; mp 103-105 °C (from DCM); [α] 20 D -29.9 (CHCl 3 , c 0.10); 1 H NMR (400 MHz, CDCl 3 ) δ 7.42-7.48 (m, 2H), 7.28-7.35 (m, 3H), 5.06 (t, J = 9.3 Hz, 1H, H-3), 4.93 (t, J = 9.6 Hz, 1H, H-2), 4.75 (d, J = 10.0 Hz, 1H, H-1), 3.93 (dd, J = 3.2, 12.1 Hz, 1H, H-6a/6b), 3.81 (dd, J = 4.6, 12.1 Hz, 1H, H-6a/6b), 3.72 (t, J = 9.5 Hz, 1H, H-4), 3.45 (ddd, J = 3.4, 4.6, 9.7 Hz, 1H, H-5), 3.10 (br.s, 1H, OH-4), 2.30 (br.s, 1H, OH-6), 2.08 (s, 3H), 2.07 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ 171.6, 169.7, 132.6 (2× C), 132.2, 129.2 (2× C), 128.4, 85.9 (C-1), 79.8 (C-5), 77.2 (C-3), 70.2 (C-2), 69.2 (C-4), 62.3 (C-6), 21.0, 20.9; HRMS (AJS-ESI): calculated for C 16 H 20 O 7 SNa [M + Na] + 379.0822, found 379.0825; NMR matches with literature data.…”

“…6 In chemical synthesis, a selective manipulation of protection groups of the saccharides is crucial as general synthetic targets are molecules with specific glycosidic bonds. [7][8][9] The synthesis of glycosyl acceptors is usually a multi-step procedure using various temporary and permanent protection groups. 10 To minimise the number of steps needed to obtain the target molecule different tools have been utilised including enzymes.…”

Modular synthesis and immunological evaluation of suspected allergenic galactooligosaccharides

“…4PX was recently synthesized by Saito and coworkers using a chemo-enzymatic approach. 18 However, this approach does not allow for the synthesis of a broad collection of GOS derivatives.…”