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【结 构 式】

【分子编号】16944

【品名】(1S,2R)-2-(benzoyloxy)-1-[(1S)-1-(hexacosanoylamino)-2-hydroxyethyl]hexadecyl benzoate

【CA登记号】

【 分 子 式 】C58H97NO6

【 分 子 量 】904.41132

【元素组成】C 77.03% H 10.81% N 1.55% O 10.61%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XIII)

The condensation of 3,4,6-O-tribenzyl-D-galactopyranose (I) with tridecyltriphenylphosphonium bromide (II) by treating first (I) with NaIO4 in aqueous ethanol, and then the resulting product with (II) and butyllithium in THF, gives the partially benzylated unsaturated tetraol (III), which is reduced with H2 over Pd/C in THF to the corresponding saturated compound (IV). The mesylation of (IV) with mesyl chloride and pyridine yields the mesylate (V), which by reaction with sodium azide in DMF is converted into the azido compound (VI). The reduction of (VI) with H2 over Pd/C in THF affords the corresponding amine (VII), which is acylated with hexacosanoic acid (VIII) by means of 2-chloro-1-methylpyridinium iodide (CMPI) in refluxing dichloromethane to give the amide (IX). The debenzylation of (IX) by hydrogenation with H2 over Pd/C in THF/propanol yields the trihydroxylated amide (X), which is selectively triphenylmethylated at the primary alcohol with trityl chloride and dimethylaminopyridine (DMAP) yielding the monotrityl derivative (XI). The subsequent protection of the secondary hydroxy groups with benzoyl chloride and DMAP affords the monotrityl dibenzoate derivative (XII), which is selectively deprotected with p-toluenesulfonic acid in methanol/water yielding the primary alcohol (XIII). The condensation of (XIII) with 2,3,4,6-O-tetrabenzyl-D-galactopyranosyl fluoride (XIV) by means of SnCl2 and AgClO4 in THF gives the fully protected final product (XV), which is first debenzylated by hydrogenation with H2 over Pd in ethyl acetate to the dibenzoate (XVI). Finally, this compound is debenzoylated by hydrolysis with sodium methoxide in methanol/THF.

1 Hoshi, A.; Castañer, J.; KRN-7000. Drugs Fut 1996, 21, 2, 152.
2 Morita, M.; Motoki, K.; Akimoto, K.; Natori, T.; Sakai, T.; Sawa, E.; Yamaji, K.; Koezuka, Y.; Kobayashi, E.; Fukushima, H.; Structure-activity relationship of alpha-galactosylceramides against B16-bearing mice. J Med Chem 1995, 38, 12, 2176-87.
3 Higa, T.; Akimoto, K.; Koezuka, Y.; Sakai, T.; Morita, M.; Natori, T. (Kirin Brewery Co., Ltd.); Novel sphingoglycolipid and use thereof. EP 0609437; JP 1993508706; US 5936076; WO 9305055 .
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) 16932 (3R,4S,5R,6R)-6-(hydroxymethyl)tetrahydro-2H-pyran-2,3,4,5-tetrol; D-Galactose 59-23-4 C6H12O6 详情 详情
(II) 16933 bromo(triphenyl)tridecylphosphorane C31H42BrP 详情 详情
(III) 16934 (1R,2R,3E)-1-[(1R)-1,2-dihydroxyethyl]-2-hydroxy-3-hexadecenyl benzoate C25H40O5 详情 详情
(IV) 16935 (1R,2R)-1-[(1R)-1,2-dihydroxyethyl]-2-hydroxyhexadecyl benzoate C25H42O5 详情 详情
(V) 16936 (1S,2R)-1-[(1R)-1-amino-2-hydroxyethyl]-2-hydroxyhexadecyl benzoate C25H43NO4 详情 详情
(VI) 16937 (1S,2R)-1-[(1S)-1-azido-2-hydroxyethyl]-2-hydroxyhexadecyl benzoate C25H41N3O4 详情 详情
(VII) 16938 (1S,2R)-1-[(1S)-1-amino-2-hydroxyethyl]-2-hydroxyhexadecyl benzoate C25H43NO4 详情 详情
(VIII) 16939 hexacosanoic acid 506-46-7 C26H52O2 详情 详情
(IX) 16940 (1S,2R)-1-[(1S)-1-(hexacosanoylamino)-2-hydroxyethyl]-2-hydroxyhexadecyl benzoate C51H93NO5 详情 详情
(X) 16941 N-[(1S,2S,3R)-2,3-dihydroxy-1-(hydroxymethyl)heptadecyl]hexacosanamide C44H89NO4 详情 详情
(XI) 16942 (1R)-1-[(1S,2S)-2-(hexacosanoylamino)-1,3-dihydroxypropyl]pentadecyl benzoate C51H93NO5 详情 详情
(XII) 16943 (1S,2R)-2-(benzoyloxy)-1-[(1S)-1-(hexacosanoylamino)-2-(trityloxy)ethyl]hexadecyl benzoate C77H111NO6 详情 详情
(XIII) 16944 (1S,2R)-2-(benzoyloxy)-1-[(1S)-1-(hexacosanoylamino)-2-hydroxyethyl]hexadecyl benzoate C58H97NO6 详情 详情
(XIV) 16945 (3R,4S,5R,6R)-2-fluoro-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol C6H11FO5 详情 详情
(XV) 16946 (1S,2R)-2-(benzoyloxy)-1-[(1S)-1-(hexacosanoylamino)-2-([(2S,3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl]oxy)ethyl]hexadecyl benzoate C92H131NO11 详情 详情
(XVI) 16947 (1R)-1-((1S,2S)-1-(benzoyloxy)-2-(hexacosanoylamino)-3-[[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy]propyl)pentadecyl benzoate C64H107NO11 详情 详情
Extended Information