(2S)-2-methoxy-3-(octadecyloxy)-1-propanol -Drug Synthesis Database

【结构式】

【分子编号】40717

【品名】(2S)-2-methoxy-3-(octadecyloxy)-1-propanol

【CA登记号】

【分子式】C₂₂H₄₆O₃

【分子量】358.60544

【元素组成】C 73.69% H 12.93% O 13.38%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(V)

The reaction of (R)-O-benzylglycidol (I) with octadecanol (II) by means of NaH in hot DMF gives (R)-1-(benzyloxy)-3-(octadecyloxy)-2-propanol (III), which is methylated with methyl iodide and NaH in DMF yielding the corresponding methyl ether (IV). The debenzylation of (IV) with H2 over Pd/C in THF affords the primary alcohol (V), which is finally treated with POCl3/pyridine in CHCl3 and condensed with choline tosylate (VI) to furnish the target phosphorylcholine derivative.

参考文献中间体

合成目标

【1】 Bittman, R.; Lohmeyer, M.; Antitumor ether lipids and alkylphosphocholines. Drugs Fut 1994, 19, 11, 1021.
【2】 Barner, R.; Hirth, G.; Synthese von Glyceryätherphosphatiden. Herstellung von 1-O-octadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylchloline (`Platelet Activating Factor'), des Enantiomeren sowie einiger analoger Verbindungen. Helv Chim Acta 1982, 65, 1059-84.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	12350	Benzyl (2R)oxiranylmethyl ether; (2R)-2-[(Benzyloxy)methyl]oxirane	14618-80-5	C₁₀H₁₂O₂	详情	详情
(II)	21494	1-octadecanol	112-92-5	C₁₈H₃₈O	详情	详情
(III)	41263	(2R)-1-(benzyloxy)-3-(octadecyloxy)-2-propanol		C₂₈H₅₀O₃	详情	详情
(IV)	41264	1-([[(2R)-2-methoxy-3-(octadecyloxy)propyl]oxy]methyl)benzene; benzyl (2R)-2-methoxy-3-(octadecyloxy)propyl ether		C₂₉H₅₂O₃	详情	详情
(V)	40717	(2S)-2-methoxy-3-(octadecyloxy)-1-propanol		C₂₂H₄₆O₃	详情	详情
(VI)	41265	2-hydroxy-N,N,N-trimethyl-1-ethanaminium 4-methylbenzenesulfonate		C₁₂H₂₁NO₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Phosphitylation of 1D-2,4,5,6-tetra-O-benzyl-3-deoxy-myo-inositol (I) with benzyl tetraisopropylphosphorodiamidite (II) in the presence of diisopropylammonium tetrazolide produced phosphoramidite (III). Subsequent displacement of the remaining diisopropylamino group of (III) by 1-O-octadecyl-2-O-methyl-sn-glycerol (IV) gave phosphite ester (V), which was further oxidized to phosphate (VI) using tert-butyl hydroperoxide. Finally, removal of the benzyl protecting groups of (VI) was achieved by catalytic hydrogenation over Pearlman's catalyst.

参考文献中间体

合成目标

【1】 Qiao, L.; Nan, F.; Kunkel, M.; Gallegos, A.; Powis, G.; Kozikowski, A.P.; 3-Deoxy-D-myo-inositol 1-phosphate, 1-phosphonate, and ether lipid analogues as inhibitors of phosphatidylinositol-3-kinase signalling and cancer cell growth. J Med Chem 1998, 41, 18, 3303.
【2】 Powis, G.; Qioa, L.; Kozikowski, A.P. (Georgetown University); Inhibitors of phosphatidyl myo-inositol cycle. WO 0000206 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	40714	(1R,2S,3S,4R,6R)-2,3,4,6-tetrakis(benzyloxy)cyclohexanol	C₃₄H₃₆O₅	详情	详情
(II)	40715		C₁₃H₂₃N₂OP	详情	详情
(III)	40716		C₄₄H₅₀NO₆P	详情	详情
(IV)	40717	(2S)-2-methoxy-3-(octadecyloxy)-1-propanol	C₂₂H₄₆O₃	详情	详情
(V)	40718	benzyl (2R)-2-methoxy-3-(octadecyloxy)propyl (1R,2R,3S,4R,6R)-2,3,4,6-tetrakis(benzyloxy)cyclohexyl phosphite	C₆₃H₈₇O₉P	详情	详情
(VI)	40719	benzyl (2R)-2-methoxy-3-(octadecyloxy)propyl (1R,2R,3S,4R,6R)-2,3,4,6-tetrakis(benzyloxy)cyclohexyl phosphate	C₆₃H₈₇O₁₀P	详情	详情

Extended Information