(2S,4R)-2-[(tert-butoxycarbonyl)amino]-4-methyloctanoic acid -Drug Synthesis Database

【结构式】

【分子编号】26272

【品名】(2S,4R)-2-[(tert-butoxycarbonyl)amino]-4-methyloctanoic acid

【CA登记号】

【分子式】C₁₄H₂₇NO₄

【分子量】273.37272

【元素组成】C 61.51% H 9.96% N 5.12% O 23.41%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(X)

The preparation of the precursor amino acids is shown in Schemes 1-4. Ozonolysis of (R)-citronellol (I), followed by Wittig reaction of the resulting aldehyde (II) with methylene triphenylphosphorane gave heptenol (III). Subsequent hydrogenation of (III) over Pd/C provided the saturated alcohol (IV), which was oxidized to the corresponding aldehyde (V) by treatment with Dess-Martin reagent. Asymmetric Strecker reaction in (V) utilizing (R)-phenylglycinol (VI) and trimethylsilyl cyanide afforded a diastereomeric mixture of aminonitriles (VII). After oxidative cleavage of (VII) with lead tetraacetate, the free (2S)-amine (VIII) was separated from its minor diastereomer by column chromatography. Acid hydrolysis of the nitrile group of (VIII) gave 5-propyl-L-leucine (IX), which was protected as the tert-butyl carbamate (X) with Boc2O.

参考文献中间体

合成目标

【1】 Boger, D.L.; et al.; Total synthesis of HUN-7293. J Am Chem Soc 1999, 121, 26, 6197.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	27301	methylene(triphenyl)phosphorane		C₁₉H₁₇P	详情	详情
(A)	18845	Dess-Martin periodinane; 1,1,1-Triacetoxy-1,2-benziodoxol-3(1H)-one	87413-09-0	C₁₃H₁₃IO₈	详情	详情
(I)	26264	(3R)-3,7-dimethyl-6-octen-1-ol	1117-61-9	C₁₀H₂₀O	详情	详情
(II)	26265	(4R)-6-hydroxy-4-methylhexanal		C₇H₁₄O₂	详情	详情
(III)	26266	(3R)-3-methyl-6-hepten-1-ol		C₈H₁₆O	详情	详情
(IV)	26267	(3R)-3-methyl-1-heptanol		C₈H₁₈O	详情	详情
(V)	26268	(3R)-3-methylheptanal		C₈H₁₆O	详情	详情
(VI)	14376	(2R)-2-amino-2-phenyl-1-ethanol; (R)-(-)-2-phenylglycinol; (R)-2-amino-2-phenyl-1-ethanol	56613-80-0	C₈H₁₁NO	详情	详情
(VII)	26269	(4R)-2-[[(1R)-2-hydroxy-1-phenylethyl]amino]-4-methyloctanenitrile		C₁₇H₂₆N₂O	详情	详情
(VIII)	26270	(2S,4R)-2-amino-4-methyloctanenitrile		C₉H₁₈N₂	详情	详情
(IX)	26271	(2S,4R)-2-amino-4-methyloctanoic acid		C₉H₁₉NO₂	详情	详情
(X)	26272	(2S,4R)-2-[(tert-butoxycarbonyl)amino]-4-methyloctanoic acid		C₁₄H₂₇NO₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

Treatment of N-Boc-N-methyl-L-leucine (XXXIV) with isobutene and H2SO4 in CH2Cl2 generated tert-butyl ester (XXXV) with simultaneous removal of the Boc group. Subsequent coupling of (XXXV) with N-Boc-5-propyl-L-leucine (X) utilizing EDC and HOAt provided dipeptide (XXXVI). Selective removal of the N-Boc group of (XXXVI) was accomplished by treatment with formic acid at r.t. The resulting amine (XXXVII) was then coupled with hydroxyacid (XXXIII) to yield the target tripeptide (XXXVIII).

参考文献中间体

合成目标

【1】 Boger, D.L.; et al.; Total synthesis of HUN-7293. J Am Chem Soc 1999, 121, 26, 6197.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(X)	26272	(2S,4R)-2-[(tert-butoxycarbonyl)amino]-4-methyloctanoic acid		C₁₄H₂₇NO₄	详情	详情
(XXXIII)	26294	(2S)-4-cyano-2-hydroxybutyric acid		C₅H₇NO₃	详情	详情
(XXXIV)	26295	(2S)-2-[(tert-butoxycarbonyl)(methyl)amino]-4-methylpentanoic acid	609-23-4	C₁₂H₂₃NO₄	详情	详情
(XXXV)	26296	tert-butyl (2S)-4-methyl-2-(methylamino)pentanoate		C₁₁H₂₃NO₂	详情	详情
(XXXVI)	26297	tert-butyl (2S)-2-[[(2S,4R)-2-[(tert-butoxycarbonyl)amino]-4-methyloctanoyl](methyl)amino]-4-methylpentanoate		C₂₅H₄₈N₂O₅	详情	详情
(XXXVII)	26298	tert-butyl (2S)-2-[[(2S,4R)-2-amino-4-methyloctanoyl](methyl)amino]-4-methylpentanoate		C₂₀H₄₀N₂O₃	详情	详情
(XXXVIII)	26299	tert-butyl (2S)-2-[((2S,4R)-2-[[(2S)-4-cyano-2-hydroxybutanoyl]amino]-4-methyloctanoyl)(methyl)amino]-4-methylpentanoate		C₂₅H₄₅N₃O₅	详情	详情

合成路线3

该中间体在本合成路线中的序号：(X)

Coupling of N-Boc-5-propyl-L-leucine (X) with N-methyl-L-alanine methyl ester (XXXIX) in the presence of EDC and HOAt gave dipeptide (XL), which was deprotected with HCl in EtOAc to afford (XLI).

参考文献中间体

合成目标

【1】 Boger, D.L.; et al.; Total synthesis of HUN-7293. J Am Chem Soc 1999, 121, 26, 6197.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(X)	26272	(2S,4R)-2-[(tert-butoxycarbonyl)amino]-4-methyloctanoic acid	C₁₄H₂₇NO₄	详情	详情
(XXXIX)	26300	methyl (2S)-2-(methylamino)propanoate	C₅H₁₁NO₂	详情	详情
(XL)	26301	methyl (2S)-2-[[(2S,4R)-2-[(tert-butoxycarbonyl)amino]-4-methyloctanoyl](methyl)amino]propanoate	C₁₉H₃₆N₂O₅	详情	详情
(XLI)	26302	methyl (2S)-2-[[(2S,4R)-2-amino-4-methyloctanoyl](methyl)amino]propanoate	C₁₄H₂₈N₂O₃	详情	详情

Extended Information