(2R,3R,4R)-4-(benzyloxy)-2-[(2,2-dimethylpropanoyl)oxy]-3-(formyloxy)-4-methyl-5-oxopentyl pivalate -Drug Synthesis Database

【结构式】

【分子编号】26135

【品名】(2R,3R,4R)-4-(benzyloxy)-2-[(2,2-dimethylpropanoyl)oxy]-3-(formyloxy)-4-methyl-5-oxopentyl pivalate

【CA登记号】

【分子式】C₂₄H₃₄O₈

【分子量】450.52916

【元素组成】C 63.98% H 7.61% O 28.41%

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：(IV)

Hexose derivative (I), prepared from D-glucose (Carbohydrat Res 1973, 108; ibid. 1975, 44: 275), was converted to dipivaloate ester (II) using pivaloyl chloride and pyridine. Then, ketal hydrolysis of (II) with aqueous TFA gave diol (III) as an anomeric mixture. Glycol cleavage in (III) by means of NaIO4 produced the acyclic aldopentose (IV). Subsequent removal of formate ester of (IV), followed by protection of the hydroxyl group provided the metoxymethyl ether (V). Wittig condensation of (V) with n-pentylidene triphenyl phosphorane yielded olefin (VI). Simultaneous hydrogenation of the double bond of (VI) and benzyl group hydrogenolysis in the presence of Pd/C furnished (VII). The methoxymethyl protecting group of (VII) was then removed by acid hydrolysis giving (VIII).

参考文献中间体

合成目标

【1】 Shiraki, R.; et al.; Total synthesis of PI-091. Tetrahedron Lett 1995, 36, 31, 5551.
【2】 Shiraki, R.; et al.; Total synthesis of natural PI-091, a new platelet aggregation inhibitor of microbial origin. J Org Chem 1996, 61, 8, 2845.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	40674	hexyl(triphenyl)phosphonium bromide	4762-26-9	C₂₄H₂₈BrP	详情	详情
(I)	26132	(1R)-1-[(3aR,5R,6R,6aR)-6-(benzyloxy)-2,2,6-trimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-1,2-ethanediol		C₁₇H₂₄O₆	详情	详情
(II)	26133	(1R)-1-[(3aR,5R,6R,6aR)-6-(benzyloxy)-2,2,6-trimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-2-[(2,2-dimethylpropanoyl)oxy]ethyl pivalate		C₂₇H₄₀O₈	详情	详情
(III)	26134	(1R)-2-(acetoxy)-1-[(2R,3S,4R)-3-(benzyloxy)-4,5-dihydroxy-3-methyltetrahydro-2-furanyl]ethyl pivalate		C₂₁H₃₀O₈	详情	详情
(IV)	26135	(2R,3R,4R)-4-(benzyloxy)-2-[(2,2-dimethylpropanoyl)oxy]-3-(formyloxy)-4-methyl-5-oxopentyl pivalate		C₂₄H₃₄O₈	详情	详情
(V)	26136	(2R,3R,4R)-4-(benzyloxy)-2-[(2,2-dimethylpropanoyl)oxy]-3-(methoxymethoxy)-4-methyl-5-oxopentyl pivalate		C₂₅H₃₈O₈	详情	详情
(VI)	26137	(2R,3R,4S,5Z)-4-(benzyloxy)-2-[(2,2-dimethylpropanoyl)oxy]-3-(methoxymethoxy)-4-methyl-5-decenyl pivalate		C₃₀H₄₈O₇	详情	详情
(VII)	26138	(2R,3R,4S)-2-[(2,2-dimethylpropanoyl)oxy]-4-hydroxy-3-(methoxymethoxy)-4-methyldecyl pivalate		C₂₃H₄₄O₇	详情	详情
(VIII)	26139	(2R,3R,4S)-2-[(2,2-dimethylpropanoyl)oxy]-3,4-dihydroxy-4-methyldecyl pivalate		C₂₁H₄₀O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

Cyclization of bromophenol (I) with 1-hexyne (II) in the presence of Pd (0) and CuI catalysts produced benzofuran (III). Then, oxidation of the aldehyde function of (III) with sodium chlorite provided carboxylic acid (IV). An alternative route to the intermediate (IV) consisted of a palladium/copper-catalyzed cyclization of bromophenol (V) with 1-hexyne (II), followed by basic hydrolysis of the resulting benzofuran methyl ester (VI). Treatment of carboxylic acid (IV) with oxalyl chloride yielded the corresponding acid chloride (VII), which was finally condensed with 4-amino-3,5-dichloropyridine (VIII) in the presence of NaEt2AlH2 to furnish the target amide.

参考文献中间体

合成目标

【1】 Hulme, C.; Travis, J.J.; Regan, J.R.; Djuric, S.W.; Sweeney, D.M.; Moriarty, K.J.; McGarry, D.G.; Miller, B.E.; Souness, J.E.; Volz, F.A.; Benzofuran based PDE4 inhibitors. Bioorg Med Chem 1999, 7, 6, 1131.

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)	26230	2-bromo-3-hydroxy-4-methoxybenzaldehyde		C₈H₇BrO₃	详情	详情
(II)	26231	1-hexyne	693-02-7	C₆H₁₀	详情	详情
(III)	26232	2-butyl-7-methoxy-1-benzofuran-4-carbaldehyde		C₁₄H₁₆O₃	详情	详情
(IV)	26233	2-butyl-7-methoxy-1-benzofuran-4-carboxylic acid		C₁₄H₁₆O₄	详情	详情
(V)	26234	methyl 2-bromo-3-hydroxy-4-methoxybenzoate		C₉H₉BrO₄	详情	详情
(VI)	26235	methyl 2-butyl-7-methoxy-1-benzofuran-4-carboxylate		C₁₅H₁₈O₄	详情	详情
(VII)	26236	2-butyl-7-methoxy-1-benzofuran-4-carbonyl chloride		C₁₄H₁₅ClO₃	详情	详情
(VIII)	26135	(2R,3R,4R)-4-(benzyloxy)-2-[(2,2-dimethylpropanoyl)oxy]-3-(formyloxy)-4-methyl-5-oxopentyl pivalate		C₂₄H₃₄O₈	详情	详情

Extended Information