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【结 构 式】

【分子编号】35428

【品名】(2R)-2-methyl-3-(triisopropylsilyl)propanal

【CA登记号】

【 分 子 式 】C13H28OSi

【 分 子 量 】228.45022

【元素组成】C 68.35% H 12.35% O 7% Si 12.29%

与该中间体有关的原料药合成路线共 4 条

合成路线1

该中间体在本合成路线中的序号:(V)

The bromination of 3,5-dimethoxybenzyl alcohol (I) with NBS gives 2-bromo-3,5-dimethoxybenzyl alcohol (II), which is treated with I2 and triphenylphosphine to yield the benzyl iodide (III). The reaction of (III) with triethyl phosphite affords the phosphonate (IV), which is condensed with the silylated aldehyde (V) by means of lithium hexamethyldisylazide (LiHMDS) giving the silylated pentenol (VI). The reaction of (VI) with chromium hexacarbonyl and BuLi provides the organochromium derivative (VII), which is cyclized with tert-butyl isocyanide and TBAF to afford the naphthalene (VIII). The benzoylation of the OH group of (VIII) with benzoyl chloride gives the benzoate (IX), which is oxidized with dichlorodicyanobenzoquinone (DDQ) to yield the naphthoquinone (X). The oxidative cyclization of (X) with O2 and TFA affords the pentacyclic quinone as a mixture of isomers that was thermally equilibrated to a 3:1 mixture of the desired isomer (XI) (the undesired isomer was recycled).The methylation of (XI) with methyl iodide and TBAF gives the fully methylated perylenequinone (XII).

1 Merlic, C.A.; et al.; Total synthesis of the calphostins: Application of fischer carbene complexes and thermodynamic control of atropisomers. J Org Chem 2001, 66, 4, 1297.
2 Merlic, C.A.; et al.; Carbene complexes in the synthesis of complex natural products: Total synthesis of the calphostins. J Am Chem Soc 2000, 122, 13, 3224.
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) 35424 (3,5-dimethoxyphenyl)methanol 705-76-0 C9H12O3 详情 详情
(II) 35425 (2-bromo-3,5-dimethoxyphenyl)methanol C9H11BrO3 详情 详情
(III) 35426 2-bromo-1-(iodomethyl)-3,5-dimethoxybenzene; 2-bromo-3-(iodomethyl)-5-methoxyphenyl methyl ether C9H10BrIO2 详情 详情
(IV) 35427 diethyl 2-bromo-3,5-dimethoxybenzylphosphonate C13H20BrO5P 详情 详情
(V) 35428 (2R)-2-methyl-3-(triisopropylsilyl)propanal C13H28OSi 详情 详情
(VI) 35429 (1R,2E)-4-(2-bromo-3,5-dimethoxyphenyl)-1-methyl-2-butenyl triisopropylsilyl ether; [[(1R,2E)-4-(2-bromo-3,5-dimethoxyphenyl)-1-methyl-2-butenyl]oxy](triisopropyl)silane C22H37BrO3Si 详情 详情
(VII) 35430   C29H45CrO9Si 详情 详情
(VIII) 35431 (2R)-1-[3-(tert-butylamino)-4,5,7-trimethoxy-2-naphthyl]-2-propanol C20H29NO4 详情 详情
(IX) 35432 (1R)-1-methyl-2-(4,5,7-trimethoxy-3-neopentyl-2-naphthyl)ethyl benzoate C28H34O5 详情 详情
(X) 35433 (1R)-2-(5,7-dimethoxy-3,4-dioxo-3,4-dihydro-2-naphthalenyl)-1-methylethyl benzoate C22H20O6 详情 详情
(XI) 35434 (1R)-2-[12-[(2R)-2-(benzoyloxy)propyl]-2,11-dihydroxy-4,6,7,9-tetramethoxy-3,10-dioxo-3,10-dihydro-1-perylenyl]-1-methylethyl benzoate C44H38O12 详情 详情
(XII) 35434 (1R)-2-[12-[(2R)-2-(benzoyloxy)propyl]-2,11-dihydroxy-4,6,7,9-tetramethoxy-3,10-dioxo-3,10-dihydro-1-perylenyl]-1-methylethyl benzoate C44H38O12 详情 详情

合成路线2

该中间体在本合成路线中的序号:(V)

The bromination of 3,5-dimethoxybenzyl alcohol (I) with NBS gives 2-bromo-3,5-dimethoxybenzyl alcohol (II), which is treated with I2 and triphenylphosphine to yield the benzyl iodide (III). The reaction of (III) with triethyl phosphite affords the phosphonate (IV), which is condensed with the silylated aldehyde (V) by means of lithium hexamethyldisylazide (LiHMDS) giving the silylated pentenol (VI). The reaction of (VI) with chromium hexacarbonyl and BuLi provides the organochromium derivative (VII), which is cyclized with tert-butyl isocyanide and TBAF to afford the naphthalene (VIII). The benzoylation of the OH group of (VIII) with benzoyl chloride gives the benzoate (IX), which is oxidized with dichlorodicyanobenzoquinone (DDQ) to yield the naphthoquinone (X). The oxidative cyclization of (X) with O2 and TFA affords the pentacyclic quinone as a mixture of isomers that was thermally equilibrated to a 3:1 mixture of the desired isomer (XI) (the undesired isomer was recycled).The methylation of (XI) with methyl iodide and TBAF gives the fully methylated perylenequinone (XII), which is selectively demethylated with MgI2 to afford the target Calpostin A.

1 Merlic, C.A.; et al.; Total synthesis of the calphostins: Application of fischer carbene complexes and thermodynamic control of atropisomers. J Org Chem 2001, 66, 4, 1297.
2 Merlic, C.A.; et al.; Carbene complexes in the synthesis of complex natural products: Total synthesis of the calphostins. J Am Chem Soc 2000, 122, 13, 3224.
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) 35424 (3,5-dimethoxyphenyl)methanol 705-76-0 C9H12O3 详情 详情
(II) 35425 (2-bromo-3,5-dimethoxyphenyl)methanol C9H11BrO3 详情 详情
(III) 35426 2-bromo-1-(iodomethyl)-3,5-dimethoxybenzene; 2-bromo-3-(iodomethyl)-5-methoxyphenyl methyl ether C9H10BrIO2 详情 详情
(IV) 35427 diethyl 2-bromo-3,5-dimethoxybenzylphosphonate C13H20BrO5P 详情 详情
(V) 35428 (2R)-2-methyl-3-(triisopropylsilyl)propanal C13H28OSi 详情 详情
(VI) 35429 (1R,2E)-4-(2-bromo-3,5-dimethoxyphenyl)-1-methyl-2-butenyl triisopropylsilyl ether; [[(1R,2E)-4-(2-bromo-3,5-dimethoxyphenyl)-1-methyl-2-butenyl]oxy](triisopropyl)silane C22H37BrO3Si 详情 详情
(VII) 35430   C29H45CrO9Si 详情 详情
(VIII) 35431 (2R)-1-[3-(tert-butylamino)-4,5,7-trimethoxy-2-naphthyl]-2-propanol C20H29NO4 详情 详情
(IX) 35432 (1R)-1-methyl-2-(4,5,7-trimethoxy-3-neopentyl-2-naphthyl)ethyl benzoate C28H34O5 详情 详情
(X) 35433 (1R)-2-(5,7-dimethoxy-3,4-dioxo-3,4-dihydro-2-naphthalenyl)-1-methylethyl benzoate C22H20O6 详情 详情
(XI) 35434 (1R)-2-[12-[(2R)-2-(benzoyloxy)propyl]-2,11-dihydroxy-4,6,7,9-tetramethoxy-3,10-dioxo-3,10-dihydro-1-perylenyl]-1-methylethyl benzoate C44H38O12 详情 详情
(XII) 35435 (1R)-2-[12-[(2R)-2-(benzoyloxy)propyl]-2,4,6,7,9,11-hexamethoxy-3,10-dioxo-3,10-dihydro-1-perylenyl]-1-methylethyl benzoate C46H42O12 详情 详情

合成路线3

该中间体在本合成路线中的序号:(V)

The bromination of 3,5-dimethoxybenzyl alcohol (I) with NBS gives 2-bromo-3,5-dimethoxybenzyl alcohol (II), which is treated with I2 and triphenylphosphine to yield the benzyl iodide (III). The reaction of (III) with triethyl phosphite affords the phosphonate (IV), which is condensed with the silylated aldehyde (V) by means of lithium hexamethyldisylazide (LiHMDS) giving the silylated pentenol (VI). The reaction of (VI) with chromium hexacarbonyl and BuLi provides the organochromium derivative (VII), which is cyclized with tert-butyl isocyanide and TBAF to afford the naphthalene (VIII). The benzoylation of the OH group of (VIII) with benzoyl chloride gives the benzoate (IX), which is oxidized with dichlorodicyanobenzoquinone (DDQ) to yield the naphthoquinone (X). The oxidative cyclization of (X) with O2 and TFA affords the pentacyclic quinone as a mixture of isomers that was thermally equilibrated to a 3:1 mixture of the desired isomer (XI) (the undesired isomer was recycled).The methylation of (XI) with methyl iodide and TBAF gives the fully methylated perylenequinone (XII).

1 Merlic, C.A.; et al.; Total synthesis of the calphostins: Application of fischer carbene complexes and thermodynamic control of atropisomers. J Org Chem 2001, 66, 4, 1297.
2 Merlic, C.A.; et al.; Carbene complexes in the synthesis of complex natural products: Total synthesis of the calphostins. J Am Chem Soc 2000, 122, 13, 3224.
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) 35424 (3,5-dimethoxyphenyl)methanol 705-76-0 C9H12O3 详情 详情
(II) 35425 (2-bromo-3,5-dimethoxyphenyl)methanol C9H11BrO3 详情 详情
(III) 35426 2-bromo-1-(iodomethyl)-3,5-dimethoxybenzene; 2-bromo-3-(iodomethyl)-5-methoxyphenyl methyl ether C9H10BrIO2 详情 详情
(IV) 35427 diethyl 2-bromo-3,5-dimethoxybenzylphosphonate C13H20BrO5P 详情 详情
(V) 35428 (2R)-2-methyl-3-(triisopropylsilyl)propanal C13H28OSi 详情 详情
(VI) 35429 (1R,2E)-4-(2-bromo-3,5-dimethoxyphenyl)-1-methyl-2-butenyl triisopropylsilyl ether; [[(1R,2E)-4-(2-bromo-3,5-dimethoxyphenyl)-1-methyl-2-butenyl]oxy](triisopropyl)silane C22H37BrO3Si 详情 详情
(VII) 35430   C29H45CrO9Si 详情 详情
(VIII) 35431 (2R)-1-[3-(tert-butylamino)-4,5,7-trimethoxy-2-naphthyl]-2-propanol C20H29NO4 详情 详情
(IX) 35432 (1R)-1-methyl-2-(4,5,7-trimethoxy-3-neopentyl-2-naphthyl)ethyl benzoate C28H34O5 详情 详情
(X) 35433 (1R)-2-(5,7-dimethoxy-3,4-dioxo-3,4-dihydro-2-naphthalenyl)-1-methylethyl benzoate C22H20O6 详情 详情
(XI) 35434 (1R)-2-[12-[(2R)-2-(benzoyloxy)propyl]-2,11-dihydroxy-4,6,7,9-tetramethoxy-3,10-dioxo-3,10-dihydro-1-perylenyl]-1-methylethyl benzoate C44H38O12 详情 详情
(XII) 35435 (1R)-2-[12-[(2R)-2-(benzoyloxy)propyl]-2,4,6,7,9,11-hexamethoxy-3,10-dioxo-3,10-dihydro-1-perylenyl]-1-methylethyl benzoate C46H42O12 详情 详情

合成路线4

该中间体在本合成路线中的序号:(V)

The bromination of 3,5-dimethoxybenzyl alcohol (I) with NBS gives 2-bromo-3,5-dimethoxybenzyl alcohol (II), which is treated with I2 and triphenylphosphine to yield the benzyl iodide (III). The reaction of (III) with triethyl phosphite affords the phosphonate (IV), which is condensed with the silylated aldehyde (V) by means of lithium hexamethyldisylazide (LiHMDS) giving the silylated pentenol (VI). The reaction of (VI) with chromium hexacarbonyl and BuLi provides the organochromium derivative (VII), which is cyclized with tert-butyl isocyanide and TBAF to afford the naphthalene (VIII). The benzoylation of the OH group of (VIII) with benzoyl chloride gives the benzoate (IX), which is oxidized with dichlorodicyanobenzoquinone (DDQ) to yield the naphthoquinone (X). The oxidative cyclization of (X) with O2 and TFA affords the pentacyclic quinone as a mixture of isomers that was thermally equilibrated to a 3:1 mixture of the desired isomer (XI) (the undesired isomer was recycled).The methylation of (XI) with methyl iodide and TBAF gives the fully methylated perylenequinone (XII).

1 Merlic, C.A.; et al.; Total synthesis of the calphostins: Application of fischer carbene complexes and thermodynamic control of atropisomers. J Org Chem 2001, 66, 4, 1297.
2 Merlic, C.A.; et al.; Carbene complexes in the synthesis of complex natural products: Total synthesis of the calphostins. J Am Chem Soc 2000, 122, 13, 3224.
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) 35424 (3,5-dimethoxyphenyl)methanol 705-76-0 C9H12O3 详情 详情
(II) 35425 (2-bromo-3,5-dimethoxyphenyl)methanol C9H11BrO3 详情 详情
(III) 35426 2-bromo-1-(iodomethyl)-3,5-dimethoxybenzene; 2-bromo-3-(iodomethyl)-5-methoxyphenyl methyl ether C9H10BrIO2 详情 详情
(IV) 35427 diethyl 2-bromo-3,5-dimethoxybenzylphosphonate C13H20BrO5P 详情 详情
(V) 35428 (2R)-2-methyl-3-(triisopropylsilyl)propanal C13H28OSi 详情 详情
(VI) 35429 (1R,2E)-4-(2-bromo-3,5-dimethoxyphenyl)-1-methyl-2-butenyl triisopropylsilyl ether; [[(1R,2E)-4-(2-bromo-3,5-dimethoxyphenyl)-1-methyl-2-butenyl]oxy](triisopropyl)silane C22H37BrO3Si 详情 详情
(VII) 35430   C29H45CrO9Si 详情 详情
(VIII) 35431 (2R)-1-[3-(tert-butylamino)-4,5,7-trimethoxy-2-naphthyl]-2-propanol C20H29NO4 详情 详情
(IX) 35432 (1R)-1-methyl-2-(4,5,7-trimethoxy-3-neopentyl-2-naphthyl)ethyl benzoate C28H34O5 详情 详情
(X) 35433 (1R)-2-(5,7-dimethoxy-3,4-dioxo-3,4-dihydro-2-naphthalenyl)-1-methylethyl benzoate C22H20O6 详情 详情
(XI) 35434 (1R)-2-[12-[(2R)-2-(benzoyloxy)propyl]-2,11-dihydroxy-4,6,7,9-tetramethoxy-3,10-dioxo-3,10-dihydro-1-perylenyl]-1-methylethyl benzoate C44H38O12 详情 详情
(XII) 35435 (1R)-2-[12-[(2R)-2-(benzoyloxy)propyl]-2,4,6,7,9,11-hexamethoxy-3,10-dioxo-3,10-dihydro-1-perylenyl]-1-methylethyl benzoate C46H42O12 详情 详情
Extended Information