1-[(2R)oxiranyl]-1-ethanone -Drug Synthesis Database

【结构式】

【分子编号】54292

【品名】1-[(2R)oxiranyl]-1-ethanone

【CA登记号】n/a

【分子式】C₄H₆O₂

【分子量】86.09044

【元素组成】C 55.81% H 7.02% O 37.17%

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：(VII)

The condensation of 3-buten-2-one (I) with the phosphonate (II) by means of LDA gives the alkylated thiazole (III), which is enantioselectively epoxidated to the chiral oxirane (V) by means of oxone and the chiral ketone (IV). Alternatively, the oxidation of the chiral epoxybutanol (VI) with CrO3 or SO3 /pyridine yields the epoxybutanone (VII), which is condensed with phosphorane (II) by means of LDA to afford the already reported chiral oxirane (V). The condensation of (V) with alkyl bromide (VIII) and propyne (IX) by means of Mg, CuBr and pentynyl lithium provides the undecatrienyl thiazole (X), which is treated with Tms-OTf in order to protect its OH group, yielding the silyl ether (XI). The oxidation of the terminal double bond of (XI) by means of (Ipc)2BH and CrO3 affords the carbaldehyde (XII), which is condensed with ketoacid (XIII) by means of LDA in THF to provide the undecadienoic acid (XIV). The cyclization of (XIV) by means of benzenesulfonyl chloride and pyridine gives the macrocyclic intermediate (XV), which is finally epoxidated by means of DMDO in acetone to furnish the target epothilone B.

参考文献中间体

合成目标

【1】 Avery, M.A. (University of Mississippi); Synthesis of epothilones and related analogs. WO 0230356 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	54294	1-pentynyllithium	n/a	C₅H₇Li	详情	详情
(I)	30324	3-buten-2-one; methyl vinyl ketone	78-94-4	C₄H₆O	详情	详情
(II)	44442	diethyl (2-methyl-1,3-thiazol-4-yl)methylphosphonate		C₉H₁₆NO₃PS	详情	详情
(III)	54290	2-methyl-4-[(1E)-2-methyl-1,3-butadienyl]-1,3-thiazole	n/a	C₉H₁₁NS	详情	详情
(IV)	54291		n/a	C₁₃H₂₀O₅	详情	详情
(V)	54293	2-methyl-4-{(E)-2-[(2R)oxiranyl]-1-propenyl}-1,3-thiazole	n/a	C₉H₁₁NOS	详情	详情
(VI)	52597	1-(2-oxiranyl)-1-ethanol		C₄H₈O₂	详情	详情
(VII)	54292	1-[(2R)oxiranyl]-1-ethanone	n/a	C₄H₆O₂	详情	详情
(VIII)	52575	5-bromo-2-methyl-1-pentene		C₆H₁₁Br	详情	详情
(IX)	51602	1-Propyne		C₃H₄	详情	详情
(X)	54295	(1E,3S,5Z)-2,6,10-trimethyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5,10-undecatrien-3-ol	n/a	C₁₈H₂₇NOS	详情	详情
(XI)	54296	2-methyl-4-{(1E,3S,5Z)-2,6,10-trimethyl-3-[(trimethylsilyl)oxy]-1,5,10-undecatrienyl}-1,3-thiazole; (1S,3Z)-4,8-dimethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3,8-nonadienyl trimethylsilyl ether	n/a	C₂₁H₃₅NOSSi	详情	详情
(XII)	54297	(2S,6Z,9S,10E)-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-9-[(trimethylsilyl)oxy]-6,10-undecadienal	n/a	C₂₁H₃₅NO₂SSi	详情	详情
(XIII)	52596	3-hydroxy-4,4-dimethyl-5-oxoheptanoic acid		C₉H₁₆O₄	详情	详情
(XIV)	54298	(3S,6R,7S,8S,12Z,15S,16E)-3,7,15-trihydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid	n/a	C₂₇H₄₃NO₆S	详情	详情
(XV)	40837	(4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione		C₂₇H₄₁NO₅S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

The condensation of 3-buten-2-one (I) with the phosphonate (II) by means of LDA gives the alkylated thiazole (III), which is enantioselectively epoxidated to the chiral oxirane (V) by means of oxone and the chiral ketone (IV). Alternatively, the oxidation of the chiral epoxybutanol (VI) with CrO3 or SO3 /pyridine yields the epoxybutanone (VII), which is condensed with phosphorane (II) by means of LDA to afford the already reported chiral oxirane (V). The condensation of (V) with alkyl bromide (VIII) and propyne (IX) by means of Mg, CuBr and pentynyl lithium provides the undecatrienyl thiazole (X), which is treated with Tms-OTf in order to protect its OH group, yielding the silyl ether (XI). The oxidation of the terminal double bond of (XI) by means of (Ipc)2BH and CrO3 affords the carbaldehyde (XII), which is condensed with ketoacid (XIII) by means of LDA in THF to provide the undecadienoic acid (XIV). Finally, the cyclization of (XIV) by means of benzenesulfonyl chloride and pyridine gives the target epothilone D.

参考文献中间体

合成目标

【1】 Avery, M.A. (University of Mississippi); Synthesis of epothilones and related analogs. WO 0230356 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	54294	1-pentynyllithium	n/a	C₅H₇Li	详情	详情
(I)	30324	3-buten-2-one; methyl vinyl ketone	78-94-4	C₄H₆O	详情	详情
(II)	44442	diethyl (2-methyl-1,3-thiazol-4-yl)methylphosphonate		C₉H₁₆NO₃PS	详情	详情
(III)	54290	2-methyl-4-[(1E)-2-methyl-1,3-butadienyl]-1,3-thiazole	n/a	C₉H₁₁NS	详情	详情
(IV)	54291		n/a	C₁₃H₂₀O₅	详情	详情
(V)	54293	2-methyl-4-{(E)-2-[(2R)oxiranyl]-1-propenyl}-1,3-thiazole	n/a	C₉H₁₁NOS	详情	详情
(VI)	52597	1-(2-oxiranyl)-1-ethanol		C₄H₈O₂	详情	详情
(VII)	54292	1-[(2R)oxiranyl]-1-ethanone	n/a	C₄H₆O₂	详情	详情
(VIII)	52575	5-bromo-2-methyl-1-pentene		C₆H₁₁Br	详情	详情
(IX)	51602	1-Propyne		C₃H₄	详情	详情
(X)	54295	(1E,3S,5Z)-2,6,10-trimethyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5,10-undecatrien-3-ol	n/a	C₁₈H₂₇NOS	详情	详情
(XI)	54296	2-methyl-4-{(1E,3S,5Z)-2,6,10-trimethyl-3-[(trimethylsilyl)oxy]-1,5,10-undecatrienyl}-1,3-thiazole; (1S,3Z)-4,8-dimethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3,8-nonadienyl trimethylsilyl ether	n/a	C₂₁H₃₅NOSSi	详情	详情
(XII)	54297	(2S,6Z,9S,10E)-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-9-[(trimethylsilyl)oxy]-6,10-undecadienal	n/a	C₂₁H₃₅NO₂SSi	详情	详情
(XIII)	52596	3-hydroxy-4,4-dimethyl-5-oxoheptanoic acid		C₉H₁₆O₄	详情	详情
(XIV)	54298	(3S,6R,7S,8S,12Z,15S,16E)-3,7,15-trihydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid	n/a	C₂₇H₄₃NO₆S	详情	详情

Extended Information