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【结 构 式】 
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【分子编号】37754 【品名】3-methyl-2-buten-1-ol 【CA登记号】556-82-1 |
【 分 子 式 】C5H10O 【 分 子 量 】86.1338 【元素组成】C 69.72% H 11.7% O 18.58% |
合成路线1
该中间体在本合成路线中的序号：(I)The cyclization of 3-methyl-2-buten-1-ol (I) with acetonitrile (II) gives 2,4,4-trimethyl-5,6-dihydro-4H-1,3-oxazine (III), which is hydrolyzed with NaOH to yield 3-amino-3-methyl-1-butanol (IV). The protection of the amino group of (IV) with (Boc)2O in isopropanol affords the carbamate (V), which is oxidized at the primary OH group with SO3/pyridine and TEA to provide the aldehyde (VI). The condensation of (VI) with triethyl phosphonoacetate (VII) by means of potassium tert-butoxide in hot toluene gives the desired hexenoic ester (intermediate 27230), which is hydrolyzed with NaOH in refluxing ethanol to yield the corresponding acid intermediate (intermediate 22191).
| 【1】 Jessen, C.U.; et al.; Synthesis of N-protected 14C-labelled (2E)-5-amino-5-methylhex-2-enoic acid analogues. J Label Compd Radiopharm 2001, 44, 4, 265. |
| 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) | 37754 | 3-methyl-2-buten-1-ol | 556-82-1 | C5H10O | 详情 | 详情 |
| (II) | 37210 | acetonitrile | 75-05-8 | C2H3N | 详情 | 详情 |
| (III) | 46630 | 2,4,4-trimethyl-5,6-dihydro-4H-1,3-oxazine | C7H13NO | 详情 | 详情 | |
| (IV) | 46631 | 3-amino-3-methyl-1-butanol | C5H13NO | 详情 | 详情 | |
| (V) | 22194 | tert-butyl 3-hydroxy-1,1-dimethylpropylcarbamate | C10H21NO3 | 详情 | 详情 | |
| (VI) | 22195 | tert-butyl 1,1-dimethyl-3-oxopropylcarbamate | C10H19NO3 | 详情 | 详情 | |
| (VII) | 10019 | Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate | 867-13-0 | C8H17O5P | 详情 | 详情 |
| (VIII) | 27230 | ethyl (E)-5-[(tert-butoxycarbonyl)amino]-5-methyl-2-hexenoate | C14H25NO4 | 详情 | 详情 | |
| (IX) | 22191 | (E)-5-[(tert-butoxycarbonyl)amino]-5-methyl-2-hexenoic acid | C12H21NO4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)Sharpless epoxidation of 3-methyl-2-buten-1-ol (I) using L-(+)-diisopropyl tartrate provided the (2S)-epoxide (II). Treatment of (II) with methyl isocyanate gave the corresponding carbamate (III). Subsequent base-catalyzed epoxide opening generated oxazolidinone (IV), which smoothly rearranged to the more stable isomer (V) under the reaction conditions. Protection of the primary alcohol of (V) as the tetrahydropyranyl ether (VII) was followed by hydrolysis of the carbamate group with KOH in aqueous ethylene glycol at 150 C. The resulting amine (VIII) was coupled with Boc-glycyl-sarcosine (IX) using EDC and HOAt to furnish amide (X). Acid-catalyzed removal of the tetrahydropyranyl group of (X) gave alcohol (XI), which was oxidized to carboxylic acid (XII) by means of RuO2-NaIO4. Exchange of the Boc protecting group for a Fmoc group in (XII) was effected by acid cleavage of the tert-butyl carbamate, followed by treatment with Fmoc-chloride. Esterification of the the resulting acid (XIII) with the functionalized dipeptide (XIV) was achieved with DCC-DMAP to produce (XV).
| 【1】 Ledeboer, M.W.; Jin, Q.; Kume, M.; Searcey, M.; Boger, D.L.; Total synthesis and comparative evaluation of luzopeptin A - C and quinoxapeptin A - C. J Am Chem Soc 1999, 121, 49, 11375. |
| 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) | 37754 | 3-methyl-2-buten-1-ol | 556-82-1 | C5H10O | 详情 | 详情 |
| (II) | 37755 | [(2S)-3,3-dimethyloxiranyl]methanol | C5H10O2 | 详情 | 详情 | |
| (III) | 37756 | [(2S)-3,3-dimethyloxiranyl]methyl methylcarbamate | C7H13NO3 | 详情 | 详情 | |
| (IV) | 37757 | (4R)-4-(1-hydroxy-1-methylethyl)-3-methyl-1,3-oxazolidin-2-one | C7H13NO3 | 详情 | 详情 | |
| (V) | 37758 | (4R)-4-(hydroxymethyl)-3,5,5-trimethyl-1,3-oxazolidin-2-one | C7H13NO3 | 详情 | 详情 | |
| (VI) | 13684 | 3,4-Dihydro-2H-pyran;2,3-Dihydro-4H-pyran; 5,6-Dihydro-4H-pyran;Dihydropyran | 110-87-2 | C5H8O | 详情 | 详情 |
| (VII) | 37759 | (4R)-3,5,5-trimethyl-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1,3-oxazolidin-2-one | C12H21NO4 | 详情 | 详情 | |
| (VIII) | 37760 | (3R)-2-methyl-3-(methylamino)-4-(tetrahydro-2H-pyran-2-yloxy)-2-butanol | C11H23NO3 | 详情 | 详情 | |
| (IX) | 18066 | N-alpha-t-BOC-glycine; 2-[(tert-butoxycarbonyl)amino]acetic acid | 4530-20-5 | C7H13NO4 | 详情 | 详情 |
| (X) | 37761 | tert-butyl 2-[[2-[[(1R)-2-hydroxy-2-methyl-1-[(tetrahydro-2H-pyran-2-yloxy)methyl]propyl](methyl)amino]-2-oxoethyl](methyl)amino]-2-oxoethylcarbamate | C21H39N3O7 | 详情 | 详情 | |
| (XI) | 37762 | tert-butyl 2-[[2-[[(1R)-2-hydroxy-1-(hydroxymethyl)-2-methylpropyl](methyl)amino]-2-oxoethyl](methyl)amino]-2-oxoethylcarbamate | C16H31N3O6 | 详情 | 详情 | |
| (XII) | 37763 | (12S)-12-(1-hydroxy-1-methylethyl)-2,2,8,11-tetramethyl-4,7,10-trioxo-3-oxa-5,8,11-triazatridecan-13-oic acid | C16H29N3O7 | 详情 | 详情 | |
| (XIII) | 37764 | (11S)-1-(9H-fluoren-9-yl)-11-(1-hydroxy-1-methylethyl)-7,10-dimethyl-3,6,9-trioxo-2-oxa-4,7,10-triazadodecan-12-oic acid | C26H31N3O7 | 详情 | 详情 | |
| (XIV) | 37765 | tert-butyl (5R)-3-[(1S,2S)-1-[(benzyloxy)carbonyl]-2-[[tert-butyl(dimethyl)silyl]oxy]-3-(1,3-dioxan-2-yl)propyl]-5-(hydroxymethyl)-10,10-dimethyl-4,7,7-trioxo-7lambda(6)-thia-2,3,6-triaza-10-silaundecan-1-oate | C34H61N3O11SSi2 | 详情 | 详情 | |
| (XV) | 37766 | tert-butyl (5R,9S)-3-[(1S,2S)-1-[(benzyloxy)carbonyl]-2-[[tert-butyl(dimethyl)silyl]oxy]-3-(1,3-dioxan-2-yl)propyl]-19-(9H-fluoren-9-yl)-9-(1-hydroxy-1-methylethyl)-10,13-dimethyl-4,8,11,14,17-pentaoxo-5-([[2-(trimethylsilyl)ethyl]sulfonyl]amino)-7,18-dioxa-2,3,10,13,16-pentaazanonadecan-1-oate | C60H90N6O17SSi2 | 详情 | 详情 |