A Convenient Synthesis of Immunosuppressive Agent FTY720 Using the Petasis Reaction

Abstract

A convenient synthesis of immunosuppressive agent FTY720 (1) using the Petasis reaction was developed. 4-Octylbenzaldehyde (9) was converted into 1-ethenyl-4-octylbenzene (11) by two-step synthesis. Hydroboration of 11 using catecholborane and hydrolysis gave (E)-2-(4-octylphenyl)vinylboronic acid (4). The Petasis reaction of 4, dihydroxyacetone (3), and benzylamine following catalytic hydrogenation afforded FTY720 (1).

New building blocks for convenient access to positional isomers of FTY720 and analogues

“…FTY720, 1 structurally contains a polar hydrophilic group, protonated 2-amino-propane-1,3-diol unit and hydrophobic 4-octylphenethyl carbon chain for its amphipathic nature. Due to the importance of the FTY720, varieties of methods are available for the synthesis of FTY720.The polar headgroup of FTY720 has been commonly installed from nitrodiol, 3 benzylamine, 4 diethyl acetamidomalonate, [5][6][7] or tris(hydroxymethyl)aminomethane (TRIS). [8][9][10] Whereas the lipophilic alkyl chain traditionally through Friedel-Crafts Acylation followed by Wolff-Kishner reduction.…”

“…After 5-10 mins, a solution of aldehyde 14 (1.500 g, 5.79 mmol) in dry DMF was added to the reaction mixture. Then reaction mixture was allowed to warm at room temperature and stirred for 4 h. After that reaction mixture was quenched by adding 5 mL saturated NH 4 Cl solution. The aqueous layer was extracted with 50 mL ethyl acetate, washed with brine (2 times).…”

Progress in Petasis Reaction

“…(9) 由于使用炔基氟硼酸钾很好地解决了炔基硼酸的 不稳定问题, 因此炔基有机硼化物的反应多采用炔基氟 硼酸钾 [36] . [72,73] , 其中最吸引人的是可方便制备一些特 殊的手性 α-氨基酸 [18] 和 β-氨基醇 [38] . …”

Efficient multi-component synthesis of 1,4-benzodiazepine-3,5-diones: a Petasis-based approach

“…4 Therefore, Petasis reaction known as the type ӀӀ MCR according to Dömling and Ugi's classification, 5 has emerged as a promising strategy for the construction of structurally diverse molecules 6-8 with biological activities. 9 Seven-membered heterocyclic rings are amongst the most appealing fragments owing to their prevalence in molecules with biological activities. Benzodiazepines, a prominent substructure in medicinal chemistry since the discovery of chlordiazepoxide and diazepam in the late 1950s, 10 represent a wide range of bioactivities.…”