Spisulosine 285, Spisulosine, ES-285, -Drug Synthesis Database

【结构式】

【药物名称】Spisulosine 285, Spisulosine, ES-285

【化学名称】2(S)-Aminooctadecan-3(R)-ol

【CA登记号】196497-48-0

【分子式】C₁₈H₃₉NO

【分子量】285.51763

【开发单位】PharmaMar (Originator), University of Illinois (Originator)

【药理作用】Oncolytic Drugs, Solid Tumors Therapy, Apoptosis Inducers, Inhibitors of Signal Transduction Pathways

合成路线1 合成路线2

合成路线1

Alanine methyl ester (I) was protected by N-alkylation with benzyl bromide to afford (II), which was further reduced to amino alcohol (III) using LiAlH4. Swern oxidation of (III) provided aldehyde (IV). Addition of the Grignard reagent obtained from 1-bromopentadecane (A) to aldehyde (IV) produced the anti-aminoalcohol (V). The N-benzyl groups were finally removed by catalytic hydrogenolysis.

参考文献中间体

【1】 Cuadros, R.; et al.; The marine compound spisulosine, an inhibitor of cell proliferation, promotes the disassembly of actin stress fibers. Cancer Letters 2000, 152, 1, 23.
【2】 Garcia Gravalos, D.; Warwick, R.A.; Avila, J.; Rinehart, K.L.; Fregeau, N.L.; Faircloth, G.T. (University of Illinois); Spisulosine cpds. having antitumour activity. WO 9952521 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(A)	47265	bromo(tetradecyl)magnesium	C₁₄H₂₉BrMg	详情	详情
(I)	20694	methyl (2S)-2-aminopropanoate	C₄H₉NO₂	详情	详情
(II)	47262	methyl (2S)-2-(dibenzylamino)propanoate	C₁₈H₂₁NO₂	详情	详情
(III)	47263	(2S)-2-(dibenzylamino)-1-propanol	C₁₇H₂₁NO	详情	详情
(IV)	47264	(2S)-2-(dibenzylamino)propanal	C₁₇H₁₉NO	详情	详情
(V)	47266	(2S,3R)-2-(dibenzylamino)-3-octadecanol	C₃₂H₅₁NO	详情	详情

合成路线2

In a different procedure, dibenzyl malonate (VI) was alkylated with tetradecyl bromide (B) to afford (VII). This was then condensed with N-phthaloyl-L-alanyl chloride (VIII) in the presence of NaH, and the resulting keto diester (IX) was subjected to hydrogenolysis of the benzyl esters and further thermal decarboxylation to furnish ketone (X). Ketone reduction with simultaneous partial reduction of the phthaloyl group yielded (XI) and (XII) as a diastereomeric mixture. After chromatographic separation, the desired isomers were deprotected by reductive cleavage with NaBH4 to provide the corresponding amino alcohol.

参考文献中间体

【1】 Cuadros, R.; et al.; The marine compound spisulosine, an inhibitor of cell proliferation, promotes the disassembly of actin stress fibers. Cancer Letters 2000, 152, 1, 23.
【2】 Garcia Gravalos, D.; Warwick, R.A.; Avila, J.; Rinehart, K.L.; Fregeau, N.L.; Faircloth, G.T. (University of Illinois); Spisulosine cpds. having antitumour activity. WO 9952521 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	47267	1-bromotetradecane	112-71-0	C₁₄H₂₉Br	详情	详情
(XIa)	47272	3-hydroxy-2-[(1S,2R)-2-hydroxy-1-methylheptadecyl]-1-isoindolinone		C₂₆H₄₃NO₃	详情	详情
(XIb)	47273	3-hydroxy-2-[(1S,2S)-2-hydroxy-1-methylheptadecyl]-1-isoindolinone		C₂₆H₄₃NO₃	详情	详情
(XIIa)	47274	2-(hydroxymethyl)-N-[(1S,2R)-2-hydroxy-1-methylheptadecyl]benzamide		C₂₆H₄₅NO₃	详情	详情
(XIIb)	47275	2-(hydroxymethyl)-N-[(1S,2S)-2-hydroxy-1-methylheptadecyl]benzamide		C₂₆H₄₅NO₃	详情	详情
(VI)	16013	dibenzyl malonate	15014-25-2	C₁₇H₁₆O₄	详情	详情
(VII)	47268	dibenzyl 2-tetradecylmalonate		C₃₁H₄₄O₄	详情	详情
(VIII)	47269	(2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoyl chloride		C₁₁H₈ClNO₃	详情	详情
(IX)	47270	dibenzyl 2-[(2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoyl]-2-tetradecylmalonate		C₄₂H₅₁NO₇	详情	详情
(X)	47271	2-[(1S)-1-methyl-2-oxoheptadecyl]-1H-isoindole-1,3(2H)-dione		C₂₆H₃₉NO₃	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)