Anisperimus, LF-15-0195, -Drug Synthesis Database

【结构式】

【药物名称】Anisperimus, LF-15-0195

【化学名称】N-[4-[3(R)-Aminobutylamino]butyl]carbamic acid N-(6-guanidinohexyl)carbamoylmethyl ester

【CA登记号】170368-04-4

【分子式】C₁₈H₃₉N₇O₃

【分子量】401.55663

【开发单位】Fournier (Originator)

【药理作用】IMMUNOMODULATING AGENTS, Immunosuppressants

合成路线1 合成路线2

合成路线1

D-Alaninol (I) was protected as the tert-butyl carbamate (II) and then converted to mesylate (III). Displacement of the mesylate group of (III) with NaCN furnished nitrile (IV), which was hydrogenated over Raney Nickel to give diamine (V). Condensation of (V) with benzaldehyde (VI) in the presence of molecular sieves produced imine (VII) and subsequent reduction by means of NaBH4 gave rise to the benzyl amine (VIII). This amine was alkylated with 4-chlorobutyronitrile (IX) to afford nitrile (X), which was further converted to the triamino compound (XI) by hydrogenation over Raney Nickel. Reaction of (XI) with methyl 2-[(phenoxycarbonyl)oxy]acetate (XII) provided carbamate (XIII). The ester group of (XIII) was then hydrolyzed with NaOH to give carboxylic acid (XIV).

参考文献中间体

【1】 Lebreton, L.; et al.; Structure - Immunosuppressive activity relationships of new analogues of 15-deoxyspergualin. 2. Structural modifications of the spermidine moiety. J Med Chem 1999, 42, 23, 4749.

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)	21414	(2R)-2-Amino-1-propanol; D-Alaninol; D-(-)-Alaninol	35320-23-1	C₃H₉NO	详情	详情
(II)	31758	tert-butyl (1R)-2-hydroxy-1-methylethylcarbamate		C₈H₁₇NO₃	详情	详情
(III)	31803	(2R)-2-[(tert-butoxycarbonyl)amino]propyl methanesulfonate		C₉H₁₉NO₅S	详情	详情
(IV)	31804	tert-butyl (1R)-2-cyano-1-methylethylcarbamate		C₉H₁₆N₂O₂	详情	详情
(V)	31805	tert-butyl (1R)-3-amino-1-methylpropylcarbamate		C₉H₂₀N₂O₂	详情	详情
(VI)	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情
(VII)	31806	tert-butyl (1R)-1-methyl-3-[[(E)-benzylidene]amino]propylcarbamate		C₁₆H₂₄N₂O₂	详情	详情
(VIII)	31807	tert-butyl (1R)-3-(benzylamino)-1-methylpropylcarbamate		C₁₆H₂₆N₂O₂	详情	详情
(IX)	11179	4-Chlorobutanenitrile; 4-Chlorobutyronitrile	628-20-6	C₄H₆ClN	详情	详情
(X)	31808	tert-butyl (1R)-3-[benzyl(3-cyanopropyl)amino]-1-methylpropylcarbamate		C₂₀H₃₁N₃O₂	详情	详情
(XI)	31809	tert-butyl (1R)-3-[(4-aminobutyl)(benzyl)amino]-1-methylpropylcarbamate		C₂₀H₃₅N₃O₂	详情	详情
(XII)	22341	methyl 2-[(phenoxycarbonyl)oxy]acetate		C₁₀H₁₀O₅	详情	详情
(XIII)	31810	methyl (6R)-9-benzyl-2,2,6-trimethyl-4,15-dioxo-3,16-dioxa-5,9,14-triazaoctadecan-18-oate		C₂₄H₃₉N₃O₆	详情	详情
(XIV)	31811	(6R)-9-benzyl-2,2,6-trimethyl-4,15-dioxo-3,16-dioxa-5,9,14-triazaoctadecan-18-oic acid		C₂₃H₃₇N₃O₆	详情	详情

合成路线2

The resulting carboxylic acid (XIV) was coupled with the Boc-protected guanidinohexylamine (XV) using DCC and HOBt to produce amide (XVI). Finally, sequential deprotection of the N-benzyl group of (XVI) by hydrogenolysis, and then cleavage of the Boc groups by means of trifluoroacetic acid yielded the target compound.

参考文献中间体

【1】 Lebreton, L.; et al.; Structure - Immunosuppressive activity relationships of new analogues of 15-deoxyspergualin. 2. Structural modifications of the spermidine moiety. J Med Chem 1999, 42, 23, 4749.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XIV)	31811	(6R)-9-benzyl-2,2,6-trimethyl-4,15-dioxo-3,16-dioxa-5,9,14-triazaoctadecan-18-oic acid	C₂₃H₃₇N₃O₆	详情	详情
(XV)	22346	tert-butyl (Z)-[(6-aminohexyl)amino][(tert-butoxycarbonyl)amino]methylidenecarbamate	C₁₇H₃₄N₄O₄	详情	详情
(XVI)	31812	(E)-11-[(tert-butoxycarbonyl)amino]-15,15-dimethyl-2,13-dioxo-14-oxa-3,10,12-triaza-11-hexadecen-1-yl 4-(benzyl[(3R)-3-[(tert-butoxycarbonyl)amino]butyl]amino)butylcarbamate	C₄₀H₆₉N₇O₉	详情	详情
(XVII)	31813	(E)-11-[(tert-butoxycarbonyl)amino]-15,15-dimethyl-2,13-dioxo-14-oxa-3,10,12-triaza-11-hexadecen-1-yl 4-([(3R)-3-[(tert-butoxycarbonyl)amino]butyl]amino)butylcarbamate	C₃₃H₆₃N₇O₉	详情	详情

Extended Information