Miltefosine synthesis

4synthesis methods

Product Name:Miltefosine
CAS Number:58066-85-6
Molecular formula:C21H46NO4P
Molecular Weight:407.57

Miltefosine is an orally- and topically-active alkyl-phosphocholine compound with potential antineoplastic activity. Miltefosine targets cellular membranes, modulating cell membrane permeability, membrane lipid composition, phospholipid metabolism, and mitogenic signal transduction, resulting in cell differentiation and inhibition of cell growth. This agent also inhibits the anti-apoptotic mitogen-activated protein kinase (MAPK) pathway and modulates the balance between the MAPK and pro-apoptotic stress-activated protein kinase (SAPK/JNK) pathways, thereby inducing apoptosis. As an immunomodulator, miltefosine stimulates T-cells, macrophages and the expression of interleukin 3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF), and interferon gamma (INF-gamma).

Synthetic Routes

ROUTE 1

ROUTE 2

ROUTE 3

Xu, Fangming; Wang, Haibo; Zhao, Jie; Liu, Xiangsheng; Li, Dandan; Chen, Chaojian; Ji, Jian. Chiral Packing of Cholesteryl Group as an Effective Strategy To Get Low Molecular Weight Supramolecular Hydrogels in the Absence of Intermolecular Hydrogen Bond. Macromolecules (Washington, DC, United States). Volume 46. Issue 11. Pages 4235-4246. Journal; Online Computer File. (2013).

Phosphoric acid, mono(2-bromoethyl) monohexadecyl ester

72358-41-9
0 suppliers
inquiry

75-50-3
263 suppliers
$15.00/25ml

58066-85-6
285 suppliers
$28.00/50mg

Yield:58066-85-6 81%

Reaction Conditions:

in chloroform;water;isopropyl alcohol;acetonitrile at 70;

Steps:

The previous compound (1.0 g, 2.33 mmol) inCHCl3/CH3CN/i-PrOH 3:5:5 (13 mL) was treated with45% (w/w) aqueous NMe3 (5 mL, 34.3 mmol) at 70°C.When all starting material was consumed (checked byTLC), volatile was removed under vacuum and the residuewas extracted with CHCl3/MeOH 1:3. The organiclayer was washed with sat. NaCl, reduced under vacuum,diluted with CHCl3, dried over MgSO4, filteredand evaporated. The crude residue was purified by flashchromatography (CH2Cl2/MeOH/H2O 75:22:3 to45:45:10) to yield miltefosine (0.77 g, 81%). Rf: 0.1(CH2Cl2/MeOH/H2O 75:22:3). 1H-NMR (400 MHz,MeOD/CDCl3 1:1) δ 0.85 (t, J = 6.2 Hz, 3H); 1.24(m, 26H); 1.61 (tt, J1 = J2 = 6.4 Hz, 2H); 3.31 (s, 9H);3.62 (m, 2H); 3.85 (td, J1 = J2 = 6.5 Hz, 2H); 4.23 (m,2H). 13C-NMR (100.7 MHz, MeOD/CDCl3 1/1) δ14.3; 23.2; 26.4; 30.1 (2C); 30.3 (8C); 31.3; 32.5;54.5; 59. 7 ; 66.7; 67.0. 31P-NMR (162 MHz ;MeOD/CDCl3 1:1) δ - 0.32. IR (ATR) ν 497; 716;746; 853; 927; 957; 1050; 1126; 1246; 1471; 1633;2849; 2914; 3372. HR-MS (ESI+) m/z [M + H]+ calcdfor C21H47NO4P+ 408.3237, found 408.3239.

References:

Gaillard, Boris;Lebeau, Luc;Remy, Jean-Serge;Pons, Fran?oise [Pharmaceutical Research,2020,vol. 37,# 6]