Synthesis of Chiral Analoguesof FTY720 and its Phosphate

Abstract

Efficient and versatile protocols for the synthesis of chiral analogues of the novel immunomodulator FTY720 and its phosphate are described. These synthetic procedures allow for broad structural variation and deliver essential tools to further elucidate FTY720's novel mechanism of action. OP), 6.86 (d, J = 8 Hz, 2 H arom ), 7.13 (d, J = 8 Hz, 2 H arom ). MS (ES+): m/z = 398.3 (MH) + , 795.3 (2 M + H) + . MS (ES-): m/z = 396.3 (M -H) -, 397.3 (M -), 793.3 (2M -H) -. (6) 1 H NMR (400 MHz, DMSO-d 6 ): d = 0.90 (t, J = 7 Hz, 3 H, CH 3 ), 1.25-1.53 [m, 10 H, CH 2 , (CH 2 ) 4 ], 1.65-1.85 (m, 6 H, 2 × C q -CH 2 , OCH 2 CH 2 ), 2.53 (m, 2 H, PhCH 2 ), 3.43 (m, 2 H, CH 2 OH), 3.88 (d, J = 7 Hz, 2 H, CH 2 OP), 3.94 (t, J = 7 Hz, 2 H, PhOCH 2 ), 6.86 (d, J = 8 Hz, 2 H arom ), 7.12 (d, J = 8 Hz, 2 H arom ). Phosphoric Acid Mono-{(S)-2-amino-2-[2-(4-heptyloxyphenyl)ethyl]-5-hydroxypentyl} EsterMS (ES+): m/z = 418.3 (MH) + , 873.4 (2 M + K) + . MS (ES-): m/z = 416.4 (M -H) -, 417.3 (M -), 833.5 (2 M -H) -.

Development of novel PP2A activators for use in the treatment of acute myeloid leukaemia

“…14 The synthesis was completed using our two-step onepot deprotection/alkylation protocol to install the hydrophobic tail, hydrolysis and reduction of the Schöllkopf group in 13 % yield over the three steps. In line with results reported by Hinterding, 15 hydrolysis of the Schöllkopf group for this substrate proved troublesome due to increased bulk of the ethyl group around the quaternary stereocentre resulting in the isolation of a considerable amount of partially hydrolysed products.…”

Iron-Catalyzed Cross-Coupling Reactions. A Scalable Synthesis of the Immunosuppressive Agent FTY720

“…The published syntheses of FTY720 start from building blocks as simple as octylbenzene, 4-octylbenzaldehyde, or 2-(4-octylphenyl)ethanol. ,, Since compounds of this type should be readily available by iron-catalyzed cross-coupling, we explored whether this methodology provides a practical and scaleable entry into this series of immunomodulating agents and meets the selectivity issues associated with the use of highly reactive Grignard reagents as the nucleophiles.…”

Efficient and scalable synthesis of 1,5-diamino-2-hydroxy-pentane from l-lysine via cascade catalysis using engineered Escherichia coli

“…Chiral amino alcohols are important chemical intermediates that have been applied in many fields because they possess active nucleophilic groups (–NH 3 , –OH) [ 1 ]. For instance, amino alcohols can string together chemical building blocks for synthesizing sphingolipids [ 2 ], antibiotics [ 3 ], and antiviral glycosidase inhibitors [ 4 ], as well as herbicides and insecticides [ 5 ]. In addition, amino alcohols can also be used in epoxy resin curing agents [ 6 ], corrosion inhibitors [ 7 ], and carbon dioxide absorbents, based on their properties of low toxicity [ 8 ], room temperature curing [ 9 ], low viscosity [ 10 ], and easy ductility [ 11 ].…”