Fig. 2: Chemical synthesis of D-sphingosine (d18:1) and D-sphingosine (d20:1) on a large scale. | Communications Chemistry

Fig. 2: Chemical synthesis of D-sphingosine (d18:1) and D-sphingosine (d20:1) on a large scale.

From: A modular chemoenzymatic cascade strategy for the structure-customized assembly of ganglioside analogs

Fig. 2

a, Structures of D-ribo-phytosphingosine and D-sphingosine (d18:1). b, Modified synthesis route of D-sphingosine (d18:1) and D-sphingosine (d20:1) from L-serine (200.0 g, 1.903 mol). Reagents and conditions: (i) methanol, AcCl (5.415 mol, 2.845 equiv), 80 °C, 2 h; (ii) (Boc)2 O (2.144 mol), TEA (4.266 mol), CH2Cl2, 20–30 °C overnight, 98% yield in two steps; (iii) imidazole (3.143 mol, 1.685 equiv), TBDMSCl (3.118 mol, 1.672 equiv), CH2Cl2, 20–30 °C overnight, 29, quantitative yield; (iv) DMMP (6.407 mol, 3.425 equiv), THF, n-BuLi (2.5 M in hexane, 6.300 mol), −75 °C, 1 h, 30, 93% yield; (v) n-tetradecanal (1.460 mol) or n-hexadecaldehyde (1.460 mol), TEA (2.892 mol), LiCl (2.854 mol, 1.646 equiv), THF, 15–20 °C, 5 h, 31: 81% yield, 32: 81% yield; (vi) LiAlH(OtBu)3 (2.997 mol, 2.130 equiv), ethanol, −78 °C, 2 h, 33: 95% yield, 34: 95% yield; (vii) HCl, methanol, 25 °C, 17 h, 35: 99% yield, 36: 99% yield; (viii) AcCl (7.314 mol), methanol, 25 °C, 15 h, 16: 60% yield, 17: 60% yield. Abbreviations: AcCl, Acyl chloride; (Boc)2O, di-tert-butyl dicarbonate; TEA, triethylamine; TBDMSCl, tert-butyldimethylsilylchloride; THF, tetrahydrofuran; DMMP, dimethyl methyl phosphonate (see more details in Supplementary II).

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