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【结 构 式】 
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【分子编号】31059 【品名】decanal 【CA登记号】112-31-2 |
【 分 子 式 】C10H20O 【 分 子 量 】156.2682 【元素组成】C 76.86% H 12.9% O 10.24% |
合成路线1
该中间体在本合成路线中的序号：(I)The Wittig condensation of decanal (I) with phosphorane (II) in benzene gives trans-2-dodecenoic acid methyl ester (III), which by thermal Michael addition of benzylamine yields the protected beta-aminoester (IV). The debenzylation of (IV) with H2 over Pd/C in methanol affords the free aminoester (V), which is condensed with N-(tert-butoxycarbonyl)-L-valine (VI) by means of 1-[3-(dimethylamino)propyl]-1-ethyl carbodiimide (WSC) in dichloromethane to give the dipeptide (VII) as a diastereomeric mixture, from which the desired isomer (VIII) is isolated by crystallization. The deprotection of the amino group of (VIII) with TFA in dichloromethane affords the peptide (IX), which is coupled with the conveniently protected glycyl-L-lysine dipeptide (X) by means of WSC as before to give the tetrapeptide (XI). The hydrolysis of the methyl ester group of (XI) with LiOH in THF/methanol/water yields the acidic tetrapeptide (XII). The intermediate glycyl-L-lysine dipeptide (X) has been obtained by coupling N-(tert-butoxycarbonyl)glycine (XV) with Nomega-(benzyloxycarbonyl)-L-lysine methyl ester (XVI) by means of WSC as before to give dipeptide (XVI), which is submitted to alkaline hydrolysis to provide the intermediate dipeptide (X).
| 【1】 Sakai, K.; Yoshioka, T.; Agematu, H.; Chiba, H.; Dobashi, K.; Rhodopeptins, novel cyclic tetrapeptides with antifungal activities from Rhodococcus sp. III. Synthetic study of rhodopeptins. J Antibiot 1999, 52, 8, 710. |
| 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) | 31059 | decanal | 112-31-2 | C10H20O | 详情 | 详情 |
| (II) | 14686 | 2-phenyl-1,3-dioxane | C10H12O2 | 详情 | 详情 | |
| (III) | 31060 | methyl (E)-2-dodecenoate | C13H24O2 | 详情 | 详情 | |
| (IV) | 31061 | methyl 3-(benzylamino)dodecanoate | C20H33NO2 | 详情 | 详情 | |
| (V) | 31062 | methyl 3-aminododecanoate | C13H27NO2 | 详情 | 详情 | |
| (VI) | 19733 | (2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid | C10H19NO4 | 详情 | 详情 | |
| (VII) | 31063 | methyl 3-([(2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutanoyl]amino)dodecanoate | C23H44N2O5 | 详情 | 详情 | |
| (VIII) | 31064 | methyl (3R)-3-([(2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutanoyl]amino)dodecanoate | C23H44N2O5 | 详情 | 详情 | |
| (IX) | 31065 | methyl (3R)-3-[[(2S)-2-amino-3-methylbutanoyl]amino]dodecanoate | C18H36N2O3 | 详情 | 详情 | |
| (X) | 31066 | (2S)-6-[[(benzyloxy)carbonyl]amino]-2-([2-[(tert-butoxycarbonyl)amino]acetyl]amino)hexanoic acid | C21H31N3O7 | 详情 | 详情 | |
| (XI) | 31067 | methyl (9S,12S,15R)-9-(4-[[(benzyloxy)carbonyl]amino]butyl)-12-isopropyl-2,2-dimethyl-15-nonyl-4,7,10,13-tetraoxo-3-oxa-5,8,11,14-tetraazaheptadecan-17-oate | C39H65N5O9 | 详情 | 详情 | |
| (XII) | 31068 | (9S,12S,15R)-9-(4-[[(benzyloxy)carbonyl]amino]butyl)-12-isopropyl-2,2-dimethyl-15-nonyl-4,7,10,13-tetraoxo-3-oxa-5,8,11,14-tetraazaheptadecan-17-oic acid | C38H63N5O9 | 详情 | 详情 | |
| (XV) | 18066 | N-alpha-t-BOC-glycine; 2-[(tert-butoxycarbonyl)amino]acetic acid | 4530-20-5 | C7H13NO4 | 详情 | 详情 |
| (XVI) | 31069 | methyl (2S)-2-amino-6-[[(benzyloxy)carbonyl]amino]hexanoate | C15H22N2O4 | 详情 | 详情 | |
| (XVII) | 31070 | methyl (2S)-6-[[(benzyloxy)carbonyl]amino]-2-([2-[(tert-butoxycarbonyl)amino]acetyl]amino)hexanoate | C22H33N3O7 | 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 condensation of decanal (I) with silyl enol ether (II) by means of a chiral catalyst and Sn(OTf)2 in dichloromethane gives the chiral thiocarboxylic ester (III), which is treated with chlorothioformate (IV) and pyridine in refluxing dichloroethane to yield the thiocarbonic ester (V). The reduction of (V) with Bu3SnH and AIBN in refluxing toluene affords the chiral thioester (VI), which is reduced with LiAlH4 in THF to provide the alcohol (VII). The oxidation of (VII) with oxalyl chloride in DMSO/dichloromethane gives the corresponding aldehyde (VIII), which is condensed with phosphorane (IX) to yield the unsaturated ester (X). The reduction of the ester group of (X) with DIBAL in dichloromethane affords the allyl alcohol (XI), which is submitted to a Sharpless epoxidation with tert-butyl hydroperoxide (TBHP) and Ti(O-iPr)4 in the presence of diethyl D-tartrate, providing the chiral epoxide (XII). Methylation of the epoxide ring of (XII) with MeLi and CuI in ethyl ether gives the diol (XIII), which is treated with the dimethyl acetal (XIV) and Ts-OH in dichloromethane to yield the 1,3-dioxane (XV). The reductive cleavage of (XV) with DIBAL in the same solvent affords the Pmb ether (XVI), whose primary alcohol is oxidized with oxalyl chloride in DMSO/dichloromethane to provide the aldehyde (XVII). The condensation of (XVII) with phosphorane (XVIII) in refluxing THF gives the unsaturated ester (XIX).
| 【1】 Wakabayashi, T.; Mori, K.; Kobayashi, S.; Total synthesis and structural elucidation of khafrefungin. J Am Chem Soc 2001, 123, 7, 1372. |
| 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) | 31059 | decanal | 112-31-2 | C10H20O | 详情 | 详情 |
| (II) | 47158 | (Z)-1-(propylsulfanyl)-1-propenyl trimethylsilyl ether; trimethyl[[(Z)-1-(propylsulfanyl)-1-propenyl]oxy]silane | C9H20OSSi | 详情 | 详情 | |
| (III) | 47159 | S-propyl (2S,3R)-3-hydroxy-2-methyldodecanethioate | C16H32O2S | 详情 | 详情 | |
| (IV) | 25805 | 1-[(chlorocarbothioyl)oxy]benzene; Phenylchlorothioformate | 1005-56-7 | C7H5ClOS | 详情 | 详情 |
| (V) | 47160 | S-propyl (2S,3R)-2-methyl-3-[(phenoxycarbothioyl)oxy]dodecanethioate | C23H36O3S2 | 详情 | 详情 | |
| (VI) | 47161 | S-propyl (2S)-2-methyldodecanethioate | C16H32OS | 详情 | 详情 | |
| (VII) | 47162 | (2S)-2-methyl-1-dodecanol | C13H28O | 详情 | 详情 | |
| (VIII) | 47163 | (2S)-2-methyldodecanal | C13H26O | 详情 | 详情 | |
| (IX) | 47164 | propyl 2-(triphenylphosphoranylidene)acetate | C23H23O2P | 详情 | 详情 | |
| (X) | 47165 | propyl (E,4S)-4-methyl-2-tetradecenoate | C18H34O2 | 详情 | 详情 | |
| (XI) | 47166 | (E,4S)-4-methyl-2-tetradecen-1-ol | C15H30O | 详情 | 详情 | |
| (XII) | 47167 | [(2S,3R)-3-[(1S)-1-methylundecyl]oxiranyl]methanol | C15H30O2 | 详情 | 详情 | |
| (XIII) | 47168 | (2S,3R,4S)-2,4-dimethyl-1,3-tetradecanediol | C16H34O2 | 详情 | 详情 | |
| (XIV) | 26485 | 1-(dimethoxymethyl)-4-methoxybenzene | 2186-92-7 | C10H14O3 | 详情 | 详情 |
| (XV) | 47169 | (4R,5S)-2-(4-methoxyphenyl)-5-methyl-4-[(1S)-1-methylundecyl]-1,3-dioxane; methyl 4-[(4R,5S)-5-methyl-4-[(1S)-1-methylundecyl]-1,3-dioxan-2-yl]phenyl ether | C24H40O3 | 详情 | 详情 | |
| (XVI) | 47170 | (2S,3R,4S)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-1-tetradecanol | C24H42O3 | 详情 | 详情 | |
| (XVII) | 47171 | (2R,3R,4S)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyltetradecanal | C24H40O3 | 详情 | 详情 | |
| (XVIII) | 47172 | propyl 2-(triphenylphosphoranylidene)propanoate | C24H25O2P | 详情 | 详情 | |
| (XIX) | 47173 | propyl (E,4S,5R,6S)-5-[(4-methoxybenzyl)oxy]-2,4,6-trimethyl-2-hexadecenoate | C30H50O4 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XI)Alkenylboronic acid (XV): The intermediate tetradecyl aldehyde derivative (XII) has been obtained by an already reported sequence (see scheme no. 23979101a, intermediates (I) to (XVII)) starting from decanal (XI). The reaction of aldehyde (XII) with CBr4 and PPh3 in dichloromethane gives the dibromovinyl derivative (XIII), which is treated with BuLi and Me-I in THF to yield the alkyne (XIV). Finally, this compound is condensed with catecholborane to provide the target alkenylboronic acid (XV).
| 【1】 Kobayashi, S.; Mori, K.; Wakabayashi, T.; Yasuda, S.; Hanada, K.; Convergent total synthesis of khafrefungin and its inhibitory activity of fungal sphigolipid syntheses. J Org Chem 2001, 66, 16, 5580. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 31059 | decanal | 112-31-2 | C10H20O | 详情 | 详情 |
| (XII) | 47171 | (2R,3R,4S)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyltetradecanal | C24H40O3 | 详情 | 详情 | |
| (XIII) | 60341 | 1-({[4,4-dibromo-2-methyl-1-(1-methylundecyl)-3-butenyl]oxy}methyl)-4-(methyloxy)benzene; 4,4-dibromo-2-methyl-1-(1-methylundecyl)-3-butenyl [4-(methyloxy)phenyl]methyl ether | C25H40Br2O2 | 详情 | 详情 | |
| (XIV) | 60342 | 1-({[2-methyl-1-(1-methylundecyl)-3-pentynyl]oxy}methyl)-4-(methyloxy)benzene; methyl 4-({[2-methyl-1-(1-methylundecyl)-3-pentynyl]oxy}methyl)phenyl ether | C26H42O2 | 详情 | 详情 | |
| (XV) | 60343 | 1,3,5-trimethyl-4-({[4-(methyloxy)phenyl]methyl}oxy)-1-pentadecenylboronic acid | C26H45BO4 | 详情 | 详情 |