(3S)-3-hydroxy-2,2-dimethyldecanoic acid -Drug Synthesis Database

【结构式】

【分子编号】42019

【品名】(3S)-3-hydroxy-2,2-dimethyldecanoic acid

【CA登记号】

【分子式】C₁₂H₂₄O₃

【分子量】216.32076

【元素组成】C 66.63% H 11.18% O 22.19%

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)

Synthesis of intermediate (V): The condensation of octanal (II) with the trimethylsilyl ether of the enol form of methyl isobutyrate (I) by means of the chiral oxazaborolidinone catalyst (III) in THF gives 3(S)-hydroxy-2,2-dimethyldecanoic acid methyl ester (IV), which is hydrolyzed with NaOH in methanol/water to yield the acid intermediate (V).

参考文献中间体

合成目标

【1】 Yokokawa, F.; et al.; Total synthesis of amamistatin A, an antiproliferative linear peptide from an actinomycete. Tetrahedron 2000, 56, 19, 3027.

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)	42016	1-Methoxy-2-methyl-1-(trimethylsiloxy)propene;1-Methoxy-2,2-dimethyl-1-(trimethylsiloxy)ethene;1-Methoxy-1-(trimethylsilyloxy)-2-methylpropene;[(1-methoxy-2-methyl-1-propenyl)oxy](trimethyl)silane; 1-methoxy-2-methyl-1-propenyl trimethylsilyl ether ;dimethylketene methyl trimethylsilyl acetal	31469-15-5	C₈H₁₈O₂Si	详情	详情
(II)	25714	octanal	124-13-0	C₈H₁₆O	详情	详情
(III)	42017	(5R)-5-isopropyl-1-[(4-methylphenyl)sulfonyl]-1,2-azaborolidin-4-one		C₁₃H₁₈BNO₃S	详情	详情
(IV)	42018	methyl (3S)-3-hydroxy-2,2-dimethyldecanoate		C₁₃H₂₆O₃	详情	详情
(V)	42019	(3S)-3-hydroxy-2,2-dimethyldecanoic acid		C₁₂H₂₄O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Synthesis of the final product: The cyclization of L-lysine (XVII) according to Miller et al. gives cyclic hydroxamate (XVIII), which is deprotected by hydrogenation with H2 over Pd/C in MeOH yielding 3-amino-1-(tert-butyldiphenylsilyloxy)perhydroazepin-2-one (XIX). The condensation of (XIX) with acid intermediate (V) by means of DEPC and TEA in DMF affords the corresponding amide (XX), which is esterified at its free OH group with acid intermediate (XVI) by means of DCC and DMAP in toluene to provide the ester (XXI). The deprotection of (XXI) with H2 over Pd/C in MeOH gives the amine (XXII), which is acylated with acid intermediate (XII) by means of EDC in CH2Cl2 to furnish the corresponding amide (XXIII). Finally this compound is deprotected with trifluoroacetic acid in CH2Cl2 to give the title product.

参考文献中间体

合成目标

【1】 Miller, M.J.; Hu, J.; Total synthesis of a mycobactin S, a siderophore and growth promoter of Mycobacterium smegmatis, and determination of its growth inhibitory activity against Mycobacterium tuberculosis. J Am Chem Soc 1997, 119, 15, 3462.
【2】 Yokokawa, F.; et al.; Total synthesis of amamistatin A, an antiproliferative linear peptide from an actinomycete. Tetrahedron 2000, 56, 19, 3027.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(V)	42019	(3S)-3-hydroxy-2,2-dimethyldecanoic acid	C₁₂H₂₄O₃	详情	详情
(XII)	42025	2-(2-hydroxy-5-methoxyphenyl)-5-methyl-1,3-oxazole-4-carboxylic acid	C₁₂H₁₁NO₅	详情	详情
(XVI)	42030	(12R)-12-[[(benzyloxy)carbonyl]amino]-8-formyl-2,2-dimethyl-5,7-dioxa-8-aza-2-silatridecan-13-oic acid	C₂₀H₃₂N₂O₇Si	详情	详情
(XVII)	17525	(2S)-6-amino-2-[[(benzyloxy)carbonyl]amino]hexanoic acid	C₁₄H₂₀N₂O₄	详情	详情
(XVIII)	42031	benzyl (3S)-1-[[tert-butyl(diphenyl)silyl]oxy]-2-oxoazepanylcarbamate	C₃₀H₃₆N₂O₄Si	详情	详情
(XIX)	42032	(3S)-3-amino-1-[[tert-butyl(diphenyl)silyl]oxy]-2-azepanone	C₂₂H₃₀N₂O₂Si	详情	详情
(XX)	42033	(3S)-N-((3S)-1-[[tert-butyl(diphenyl)silyl]oxy]-2-oxoazepanyl)-3-hydroxy-2,2-dimethyldecanamide	C₃₄H₅₂N₂O₄Si	详情	详情
(XXI)	42034	(1S)-1-[2-[((3S)-1-[[tert-butyl(diphenyl)silyl]oxy]-2-oxoazepanyl)amino]-1,1-dimethyl-2-oxoethyl]octyl (12R)-12-[[(benzyloxy)carbonyl]amino]-8-formyl-2,2-dimethyl-5,7-dioxa-8-aza-2-silatridecan-13-oate	C₅₄H₈₂N₄O₁₀Si₂	详情	详情
(XXII)	42035	(1S)-1-[2-[((3S)-1-[[tert-butyl(diphenyl)silyl]oxy]-2-oxoazepanyl)amino]-1,1-dimethyl-2-oxoethyl]octyl (12R)-12-amino-8-formyl-2,2-dimethyl-5,7-dioxa-8-aza-2-silatridecan-13-oate	C₄₆H₇₆N₄O₈Si₂	详情	详情
(XXIII)	42036	(1S)-1-[2-[((3S)-1-[[tert-butyl(diphenyl)silyl]oxy]-2-oxoazepanyl)amino]-1,1-dimethyl-2-oxoethyl]octyl (12R)-8-formyl-12-([[2-(2-hydroxy-5-methoxyphenyl)-5-methyl-1,3-oxazol-4-yl]carbonyl]amino)-2,2-dimethyl-5,7-dioxa-8-aza-2-silatridecan-13-oate	C₅₈H₈₅N₅O₁₂Si₂	详情	详情

Extended Information