3-[9-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-7-hydroxy-2,10-dimethyl-6-methylidene-11-(2-methyl-1,3-thiazol-4-yl)-10-undecenoyl]-4-(phenylmethyl)-1,3-oxazolidin-2-one -Drug Synthesis Database

【结构式】

【分子编号】52571

【品名】3-[9-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-7-hydroxy-2,10-dimethyl-6-methylidene-11-(2-methyl-1,3-thiazol-4-yl)-10-undecenoyl]-4-(phenylmethyl)-1,3-oxazolidin-2-one

【CA登记号】

【分子式】C₃₄H₅₀N₂O₅SSi

【分子量】626.93298

【元素组成】C 65.14% H 8.04% N 4.47% O 12.76% S 5.11% Si 4.48%

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：(XIV)

The allylation of 2-(2-methylthiazol-4-ylmethylene)propionaldehyde (X) with allyl(diisopinocampheyl)borane gives the chiral secondary alcohol (XI), which is protected with Tbdms-Cl, yielding the silyl ether (XII). The oxidation of the terminal double bond of (XII) with OsO4 and NaIO4 affords the chiral aldehyde (XIII), which is condensed with the intermediate iodovinyl compound (IX) by means of Ni/Cr to provide the allyl alcohol derivative (XIV). The reaction of (XIV) with SOCl2 gives the rearranged chloromethyl compound (XV), which is treated with LiEt3BH to cleave the oxazolidine chiral auxiliary and dechlorinate the chloromethyl group, yielding the primary alcohol (XVI). The controlled oxidation of the OH group of (XVI) with PCC affords the aldehyde (XVII), which is submitted to an aldol condensation with the intermediate ketone (VI) by means of LDA to provide the aldol (XVIII). The protection of the OH group of (XVIII) with Tbdms-Cl gives the fully silylated compound (XIX), which is regioselectively monodesilylated with camphorsulfonic acid (CSA) to yield the primary alcohol (XX).

参考文献中间体

合成目标

【1】 Chen, Y.; Taylor, R.E.; Total synthesis of epothilones B and D. Org Lett 2001, 3, 14, 2221.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VI)	40830	(5S)-5,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-3-heptanone	C₂₁H₄₆O₃Si₂	详情	详情
(IX)	52569	3-(6-iodo-2-methyl-6-heptenoyl)-4-(phenylmethyl)-1,3-oxazolidin-2-one	C₁₈H₂₂INO₃	详情	详情
(X)	44456	(E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenal	C₈H₉NOS	详情	详情
(XI)	43171	(1E,3S)-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5-hexadien-3-ol	C₁₁H₁₅NOS	详情	详情
(XII)	44444	4-((1E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1,5-hexadienyl)-2-methyl-1,3-thiazole; tert-butyl(dimethyl)silyl (1S)-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl ether	C₁₇H₂₉NOSSi	详情	详情
(XIII)	40822	(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenal	C₁₆H₂₇NO₂SSi	详情	详情
(XIV)	52571	3-[9-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-7-hydroxy-2,10-dimethyl-6-methylidene-11-(2-methyl-1,3-thiazol-4-yl)-10-undecenoyl]-4-(phenylmethyl)-1,3-oxazolidin-2-one	C₃₄H₅₀N₂O₅SSi	详情	详情
(XV)	52570	3-[6-(chloromethyl)-9-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2,10-dimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienoyl]-4-(phenylmethyl)-1,3-oxazolidin-2-one	C₃₄H₄₉ClN₂O₄SSi	详情	详情
(XVI)	40828	(2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadien-1-ol	C₂₄H₄₃NO₂SSi	详情	详情
(XVII)	40829	(2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienal	C₂₄H₄₁NO₂SSi	详情	详情
(XVIII)	40831	(7S,10R,11S,12S,16Z,19S)-7-[[tert-butyl(dimethyl)silyl]oxy]-11-hydroxy-2,2,3,3,8,8,10,12,16,21,21,22,22-tridecamethyl-19-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,20-dioxa-3,21-disila-16-tricosen-9-one	C₄₅H₈₇NO₅SSi₃	详情	详情
(XIX)	40832	(7S,10R,11S,12S,16Z,19S)-7,11-bis[[tert-butyl(dimethyl)silyl]oxy]-2,2,3,3,8,8,10,12,16,21,21,22,22-tridecamethyl-19-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,20-dioxa-3,21-disila-16-tricosen-9-one	C₅₁H₁₀₁NO₅SSi₄	详情	详情
(XX)	40833	(5S,8R,9S,10S,14Z,17S)-9-[[tert-butyl(dimethyl)silyl]oxy]-5-(2-hydroxyethyl)-2,2,3,3,6,6,8,10,14,19,19,20,20-tridecamethyl-17-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,18-dioxa-3,19-disila-14-henicosen-7-one	C₄₅H₈₇NO₅SSi₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The intermediate carboxylic acid (V) has been obtained as follows: The reaction of the chiral auxiliary oxazolidinone (I) with the oxoaldehyde (II) by means of Bu2B-OTf, DIEA and Raney Ni in dichloromethane gives the oxazolidide (III), which is treated with Tbdms-OTf, yielding the silyl ether (IV), which is easily purified. Elimination of the auxiliary with LiOH and H2O2 in THF/water affords the target carboxylic acid (V).

参考文献中间体

合成目标

【1】 Valluri, M.; et al.; Total synthesis of epothilone B. Org Lett 2001, 3, 23, 3607.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	52571	3-[9-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-7-hydroxy-2,10-dimethyl-6-methylidene-11-(2-methyl-1,3-thiazol-4-yl)-10-undecenoyl]-4-(phenylmethyl)-1,3-oxazolidin-2-one	C₃₄H₅₀N₂O₅SSi	详情	详情
(II)	44448	2,2-dimethyl-3-oxopentanal	C₇H₁₂O₂	详情	详情
(III)	52572	4-(1-methylethyl)-3-[2-(methylsulfanyl)acetyl]-1,3-oxazolidin-2-one	C₉H₁₅NO₃S	详情	详情
(IV)	52573	3-hydroxy-4,4-dimethyl-1-[4-(1-methylethyl)-2-oxo-1,3-oxazolidin-3-yl]-1,5-heptanedione	C₁₅H₂₅NO₅	详情	详情
(V)	43166	(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanoic acid	C₁₅H₃₀O₄Si	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XIV)

参考文献中间体

合成目标

【1】 Chen, Y.; Taylor, R.E.; Total synthesis of epothilones B and D. Org Lett 2001, 3, 14, 2221.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VI)	40830	(5S)-5,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-3-heptanone	C₂₁H₄₆O₃Si₂	详情	详情
(IX)	52569	3-(6-iodo-2-methyl-6-heptenoyl)-4-(phenylmethyl)-1,3-oxazolidin-2-one	C₁₈H₂₂INO₃	详情	详情
(X)	44456	(E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenal	C₈H₉NOS	详情	详情
(XI)	43171	(1E,3S)-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5-hexadien-3-ol	C₁₁H₁₅NOS	详情	详情
(XII)	44444	4-((1E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1,5-hexadienyl)-2-methyl-1,3-thiazole; tert-butyl(dimethyl)silyl (1S)-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl ether	C₁₇H₂₉NOSSi	详情	详情
(XIII)	40822	(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenal	C₁₆H₂₇NO₂SSi	详情	详情
(XIV)	52571	3-[9-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-7-hydroxy-2,10-dimethyl-6-methylidene-11-(2-methyl-1,3-thiazol-4-yl)-10-undecenoyl]-4-(phenylmethyl)-1,3-oxazolidin-2-one	C₃₄H₅₀N₂O₅SSi	详情	详情
(XV)	52570	3-[6-(chloromethyl)-9-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2,10-dimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienoyl]-4-(phenylmethyl)-1,3-oxazolidin-2-one	C₃₄H₄₉ClN₂O₄SSi	详情	详情
(XVI)	40828	(2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadien-1-ol	C₂₄H₄₃NO₂SSi	详情	详情
(XVII)	40829	(2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienal	C₂₄H₄₁NO₂SSi	详情	详情
(XVIII)	40831	(7S,10R,11S,12S,16Z,19S)-7-[[tert-butyl(dimethyl)silyl]oxy]-11-hydroxy-2,2,3,3,8,8,10,12,16,21,21,22,22-tridecamethyl-19-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,20-dioxa-3,21-disila-16-tricosen-9-one	C₄₅H₈₇NO₅SSi₃	详情	详情
(XIX)	40832	(7S,10R,11S,12S,16Z,19S)-7,11-bis[[tert-butyl(dimethyl)silyl]oxy]-2,2,3,3,8,8,10,12,16,21,21,22,22-tridecamethyl-19-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,20-dioxa-3,21-disila-16-tricosen-9-one	C₅₁H₁₀₁NO₅SSi₄	详情	详情
(XX)	40833	(5S,8R,9S,10S,14Z,17S)-9-[[tert-butyl(dimethyl)silyl]oxy]-5-(2-hydroxyethyl)-2,2,3,3,6,6,8,10,14,19,19,20,20-tridecamethyl-17-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,18-dioxa-3,19-disila-14-henicosen-7-one	C₄₅H₈₇NO₅SSi₃	详情	详情

Extended Information