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【结 构 式】 
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【分子编号】35426 【品名】2-bromo-1-(iodomethyl)-3,5-dimethoxybenzene; 2-bromo-3-(iodomethyl)-5-methoxyphenyl methyl ether 【CA登记号】 |
【 分 子 式 】C9H10BrIO2 【 分 子 量 】356.98567 【元素组成】C 30.28% H 2.82% Br 22.38% I 35.55% O 8.96% |
合成路线1
该中间体在本合成路线中的序号：(III)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：(III)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：(III)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：(III)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 |