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【结 构 式】 
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【分子编号】61148 【品名】(2S)-4-methyl-3,6-dihydro-2H-pyran-2-carbaldehyde 【CA登记号】 |
【 分 子 式 】C7H10O2 【 分 子 量 】126.1552 【元素组成】C 66.65% H 7.99% O 25.36% |
合成路线1
该中间体在本合成路线中的序号：(XXVI)The synthesis of the phosphonate intermediate (XXXVII) has been performed as follows: The reaction of the 2-hexynoic ester (XVIII) with Tbdps-Cl gives the silyl ether (XIX), which is reduced with DIBAL to yield the propargyl alcohol (XX). The protection of (XX) by reaction with dihydropyran affords the tetrahydropyranyl ether (XXI), which is selectively deprotected by means of DDQ to provide the acetylenic alcohol (XXII). The oxidation of (XXII) by means of SO3/pyridine, and NaClO2, followed by methylation with diazomethane gives the acetylenic ester (XXIII), which is condensed with phosphonate (XXIV) by means of BuLi to yield the chiral phosphonate (XXV). The condensation of (XXV) with 4-methyl-3,6-dihydro-2H-pyran-2(S)-carbaldehyde (XXVI) affords the ketonic adduct (XXVII), which is reduced with NaBH4 and CeCl3 to provide the secondary alcohol (XXVIII). The reaction of (XXVIII) with Mom-Cl gives the corresponding Mom-ether (XXIX), whose tetrahydropyranyl group is hydrolyzed by means of HCl to yield the primary alcohol (XXX). The selective monoreduction of the acetylenic triple bond of (XXX) by means of Red-Al affords the octadienyl alcohol (XXXI), which is oxidized with DMP to the expected aldehyde (XXXII). The reaction of (XXXII) with (R,R)-pentane-2,4-diol (XXXIII) affords the propylene ketal (XXXIV), which is desilylated by means of TBAF to provide the secondary alcohol (XXXV). The condensation of (XXXV) with the phosphonoacetic acid (XXXVI) furnishes the corresponding ester (XXXVII).
| 【1】 Ahmed, A.; Hoegenauer, E.K.; Enev, V.S.; Hanbauer, M.; Kaehlig, H.; Ohler, E.; Mulzer, J.; Total synthesis of the microtubule stabilizing antitumor agent laulimalide and some nonnatural analogues: The power of Sharpless' asymmetric epoxidation. J. Org. Chem. 2003, 68, 8, 3026. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVIII) | 61141 | propyl (5S)-5-hydroxy-6-[(4-methoxybenzyl)oxy]-2-hexynoate | C17H22O5 | 详情 | 详情 | |
| (XIX) | 61142 | propyl (5S)-5-{[tert-butyl(diphenyl)silyl]oxy}-6-[(4-methoxybenzyl)oxy]-2-hexynoate | C33H40O5Si | 详情 | 详情 | |
| (XX) | 61143 | (5S)-5-{[tert-butyl(diphenyl)silyl]oxy}-6-[(4-methoxybenzyl)oxy]-2-hexyn-1-ol | C30H36O4Si | 详情 | 详情 | |
| (XXI) | 61144 | tert-butyl{[(1S)-1-{[(4-methoxybenzyl)oxy]methyl}-5-(tetrahydro-2H-pyran-2-yloxy)-3-pentynyl]oxy}diphenylsilane; tert-butyl(diphenyl)silyl (1S)-1-{[(4-methoxybenzyl)oxy]methyl}-5-(tetrahydro-2H-pyran-2-yloxy)-3-pentynyl ether | C35H44O5Si | 详情 | 详情 | |
| (XXII) | 61145 | (2S)-2-{[tert-butyl(diphenyl)silyl]oxy}-6-(tetrahydro-2H-pyran-2-yloxy)-4-hexyn-1-ol | C27H36O4Si | 详情 | 详情 | |
| (XXIII) | 61146 | methyl (2S)-2-{[tert-butyl(diphenyl)silyl]oxy}-6-(tetrahydro-2H-pyran-2-yloxy)-4-hexynoate | C28H36O5Si | 详情 | 详情 | |
| (XXIV) | 13607 | dimethyl methylphosphonate | 756-79-6 | C3H9O3P | 详情 | 详情 |
| (XXV) | 61147 | dimethyl (3S)-3-{[tert-butyl(diphenyl)silyl]oxy}-2-oxo-7-(tetrahydro-2H-pyran-2-yloxy)-5-heptynylphosphonate | C30H41O7PSi | 详情 | 详情 | |
| (XXVI) | 61148 | (2S)-4-methyl-3,6-dihydro-2H-pyran-2-carbaldehyde | C7H10O2 | 详情 | 详情 | |
| (XXVII) | 61149 | (E,4S)-4-{[tert-butyl(diphenyl)silyl]oxy}-1-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-8-(tetrahydro-2H-pyran-2-yloxy)-1-octen-6-yn-3-one | C35H44O5Si | 详情 | 详情 | |
| (XXVIII) | 61150 | (E,3S,4S)-4-{[tert-butyl(diphenyl)silyl]oxy}-1-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-8-(tetrahydro-2H-pyran-2-yloxy)-1-octen-6-yn-3-ol | C35H46O5Si | 详情 | 详情 | |
| (XXIX) | 61151 | (5S,6S)-9,9-dimethyl-5-{(E)-2-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]ethenyl}-8,8-diphenyl-6-[4-(tetrahydro-2H-pyran-2-yloxy)-2-butynyl]-2,4,7-trioxa-8-siladecane; tert-butyl(diphenyl)silyl (1S)-1-{(1S,2E)-1-(methoxymethoxy)-3-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-2-propenyl}-5-(tetrahydro-2H-pyran-2-yloxy)-3-pentynyl ether | C37H50O6Si | 详情 | 详情 | |
| (XXX) | 61152 | (5S,6S,7E)-5-{[tert-butyl(diphenyl)silyl]oxy}-6-(methoxymethoxy)-8-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-7-octen-2-yn-1-ol | C32H42O5Si | 详情 | 详情 | |
| (XXXI) | 61153 | (2E,5S,6S,7E)-5-{[tert-butyl(diphenyl)silyl]oxy}-6-(methoxymethoxy)-8-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-2,7-octadien-1-ol | C32H44O5Si | 详情 | 详情 | |
| (XXXII) | 61154 | (2E,5S,6S,7E)-5-{[tert-butyl(diphenyl)silyl]oxy}-6-(methoxymethoxy)-8-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-2,7-octadienal | C32H42O5Si | 详情 | 详情 | |
| (XXXIII) | 57935 | (2S,4S)-2,4-pentanediol | C5H12O2 | 详情 | 详情 | |
| (XXXIV) | 61155 | tert-butyl(diphenyl)silyl (1S,2S,3E)-1-{(E)-3-[(4R,6R)-4,6-dimethyl-1,3-dioxan-2-yl]-2-propenyl}-2-(methoxymethoxy)-4-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-3-butenyl ether; (5S,6S)-6-{(E)-3-[(4R,6R)-4,6-dimethyl-1,3-dioxan-2-yl]-2-propenyl}-9,9-dimethyl-5-{(E)-2-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]ethenyl}-8,8-diphenyl-2,4,7-trioxa-8-siladecane | C37H52O6Si | 详情 | 详情 | |
| (XXXV) | 61156 | (1E,3S,4S,6E)-7-[(4R,6R)-4,6-dimethyl-1,3-dioxan-2-yl]-3-(methoxymethoxy)-1-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-1,6-heptadien-4-ol | C21H34O6 | 详情 | 详情 | |
| (XXXVI) | 61157 | 2-[bis(2,2,2-trifluoroethoxy)phosphoryl]acetic acid | C6H7F6O5P | 详情 | 详情 | |
| (XXXVII) | 61158 | (1S,2S,3E)-1-{(E)-3-[(4R,6R)-4,6-dimethyl-1,3-dioxan-2-yl]-2-propenyl}-2-(methoxymethoxy)-4-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-3-butenyl 2-[bis(2,2,2-trifluoroethoxy)phosphoryl]acetate | C27H39F6O10P | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XIII)The intermediate 4-methyl-3,6-dihydro-2H-pyran-2(S)-carbaldehyde (XIII) has been obtained as follows: The cyclization of 2-(Tbdms-O)acetaldehyde (IX) with 1-methoxy-3-methylbutadiene (X) by means of a chiral Cr catalyst gives the chiral dihydropyran derivative (XI), which is desilylated and demethoxylated by means of triethylsilane, BF3/Et2O and HCl to yield the dihydropyran methanol derivative (XII). Finally, this compound is oxidized to the target intermediate 4-methyl-3,6-dihydro-2H-pyran-2(S)-carbaldehyde (XIII) by means of oxalyl chloride , DMSO and TEA
| 【1】 Paterson, I.; et al.; Total synthesis of the microtubule-stabilizing agent (-)-laulimalide. Org Lett 2001, 3, 20, 3149. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 61170 | 2-{[tert-butyl(dimethyl)silyl]oxy}acetaldehyde；tert-butyldimethylsilyloxy acetaldehyde | 102191-92-4 | C8H18O2Si | 详情 | 详情 |
| (X) | 61171 | (1E)-1-methoxy-3-methyl-1,3-butadiene; methyl (1E)-3-methyl-1,3-butadienyl ether | C6H10O | 详情 | 详情 | |
| (XI) | 61172 | tert-butyl(dimethyl)silyl [(2S,6R)-6-methoxy-4-methyl-3,6-dihydro-2H-pyran-2-yl]methyl ether; tert-butyl{[(2S,6R)-6-methoxy-4-methyl-3,6-dihydro-2H-pyran-2-yl]methoxy}dimethylsilane | C14H28O3Si | 详情 | 详情 | |
| (XII) | 61173 | [(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]methanol | C7H12O2 | 详情 | 详情 | |
| (XIII) | 61148 | (2S)-4-methyl-3,6-dihydro-2H-pyran-2-carbaldehyde | C7H10O2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XIII)The intermediate octadienal derivative (XXXI) has been obtained as follows: The selective monosilylation of 3(R),4-dihydroxybutyric acid methyl ester (XIV) by means of Tbdms-Cl and imidazole in dichloromethane gives the terminal silyl ether (XV), which is treated with PmbOC(=NH)CCl3 and TfOH in ethyl ether to yield the fully protected compound (XVI). The reduction of the ester group of (XVI) by means of LiAlH4 in THF affords the butanol derivative (XVII), which is subjected to Dess-Martin oxidation to furnish the corresponding aldehyde (XVIII). The condensation of (XVIII) with phosphonate (XIX) by means of DIEA and LiCl in acetonitrile provides the hexenoic ester (XX), which is reduced with DIBAL to the corresponding unsaturated alcohol (XXI). The reaction of (XXI) with Tbdps-Cl and imidazole gives the silyl ether (XXII), which is selectively monodesilylated by means of TsOH in ethanol to yield the alcohol (XXIII). The Swern oxidation of (XXIII) affords the corresponding aldehyde (XXIV), which is methylated with MeMgCl to provide the secondary alcohol (XXV). The Swern oxidation of (XXXV) yields the methyl ketone (XXVI), which is condensed with the intermediate 4-methyl-3,6-dihydro-2H-pyran-2(S)-carbaldehyde (XIII) by means of (cHex)2BCl and TEA, followed by a treatment with MsCl and TEA to afford the octadienone (XXVII). The reduction of (XXVII) by means of Zn(BH4)2 in ethyl ether provides the octadienol (XXVIII), which is silylated with Tbdms-OTf and lutidine to give the silyl ether (XXIX). The selective monodeprotection of (XXIX) by means of TBAF in AcOH yields the octadienol (XXX), which is oxidized with DMP to afford the intermediate octadienal derivative (XXXI)
| 【1】 Paterson, I.; et al.; Total synthesis of the microtubule-stabilizing agent (-)-laulimalide. Org Lett 2001, 3, 20, 3149. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIII) | 61148 | (2S)-4-methyl-3,6-dihydro-2H-pyran-2-carbaldehyde | C7H10O2 | 详情 | 详情 | |
| (XIV) | 11807 | methyl (3S)-3,4-dihydroxybutanoate | C5H10O4 | 详情 | 详情 | |
| (XV) | 61174 | methyl (3R)-4-{[tert-butyl(dimethyl)silyl]oxy}-3-hydroxybutanoate | C11H24O4Si | 详情 | 详情 | |
| (XVI) | 61175 | methyl (3R)-4-{[tert-butyl(dimethyl)silyl]oxy}-3-[(4-methoxybenzyl)oxy]butanoate | C19H32O5Si | 详情 | 详情 | |
| (XVII) | 61176 | (3R)-4-{[tert-butyl(dimethyl)silyl]oxy}-3-[(4-methoxybenzyl)oxy]-1-butanol | C18H32O4Si | 详情 | 详情 | |
| (XVIII) | 61177 | (3R)-4-{[tert-butyl(dimethyl)silyl]oxy}-3-[(4-methoxybenzyl)oxy]butanal | C18H30O4Si | 详情 | 详情 | |
| (XX) | 61178 | methyl (E,5R)-6-{[tert-butyl(dimethyl)silyl]oxy}-5-[(4-methoxybenzyl)oxy]-2-hexenoate | C21H34O5Si | 详情 | 详情 | |
| (XXI) | 61179 | (E,5R)-6-{[tert-butyl(dimethyl)silyl]oxy}-5-[(4-methoxybenzyl)oxy]-2-hexen-1-ol | C20H34O4Si | 详情 | 详情 | |
| (XXII) | 61180 | (E,9R)-9-[(4-methoxybenzyl)oxy]-2,2,12,12,13,13-hexamethyl-3,3-diphenyl-4,11-dioxa-3,12-disila-6-tetradecene; tert-butyl(dimethyl)silyl (2R,4E)-6-{[tert-butyl(diphenyl)silyl]oxy}-2-[(4-methoxybenzyl)oxy]-4-hexenyl ether | C36H52O4Si2 | 详情 | 详情 | |
| (XXIII) | 61181 | (2R,4E)-6-{[tert-butyl(diphenyl)silyl]oxy}-2-[(4-methoxybenzyl)oxy]-4-hexen-1-ol | C30H38O4Si | 详情 | 详情 | |
| (XXIV) | 61182 | (2R,4E)-6-{[tert-butyl(diphenyl)silyl]oxy}-2-[(4-methoxybenzyl)oxy]-4-hexenal | C30H36O4Si | 详情 | 详情 | |
| (XXV) | 61183 | (3R,5E)-7-{[tert-butyl(diphenyl)silyl]oxy}-3-[(4-methoxybenzyl)oxy]-5-hepten-2-ol | C31H40O4Si | 详情 | 详情 | |
| (XXVI) | 61184 | (3R,5E)-7-{[tert-butyl(diphenyl)silyl]oxy}-3-[(4-methoxybenzyl)oxy]-5-hepten-2-one | C31H38O4Si | 详情 | 详情 | |
| (XXVII) | 61185 | (1E,4R,6E)-8-{[tert-butyl(diphenyl)silyl]oxy}-4-[(4-methoxybenzyl)oxy]-1-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-1,6-octadien-3-one | C38H46O5Si | 详情 | 详情 | |
| (XXVIII) | 61186 | (1E,3S,4R,6E)-8-{[tert-butyl(diphenyl)silyl]oxy}-4-[(4-methoxybenzyl)oxy]-1-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-1,6-octadien-3-ol | C38H48O5Si | 详情 | 详情 | |
| (XXIX) | 61187 | (E,9R,10S)-9-[(4-methoxybenzyl)oxy]-2,2,12,12,13,13-hexamethyl-10-{(E)-2-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]ethenyl}-3,3-diphenyl-4,11-dioxa-3,12-disila-6-tetradecene; tert-butyl(dimethyl)silyl (1S,2R,4E)-6-{[tert-butyl(diphenyl)silyl]oxy}-2-[(4-methoxybenzyl)oxy]-1-{(E)-2-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]ethenyl}-4-hexenyl ether | C44H62O5Si2 | 详情 | 详情 | |
| (XXX) | 61188 | (2E,5R,6S,7E)-6-{[tert-butyl(dimethyl)silyl]oxy}-5-[(4-methoxybenzyl)oxy]-8-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-2,7-octadien-1-ol | C28H44O5Si | 详情 | 详情 | |
| (XXXI) | 61189 | (2E,5R,6S,7E)-6-{[tert-butyl(dimethyl)silyl]oxy}-5-[(4-methoxybenzyl)oxy]-8-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-2,7-octadienal | C28H42O5Si | 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 synthesis of the 1,3-dioxane intermediate (XIII) has been performed as follows: The reaction of 2(S)-hydroxycyclopentanone (I) with Tbdps-Cl and imidazole in DMF gives the silyl ether (II), which is condensed with the phosphonate (III) by means of BuLi in THF to yield the new phosphonate (IV) after silylation with Tes-Cl and LDA. The Horner-Wadsworth-Emmons olefination of carbaldehyde (V) with phosphonate (IV) by means of LiCl and TEA in THF affords the silylated ketone (VI), which is reduced with NaBH4/CeCl3 and protected with Mom-Cl and DIEA to provide the dihydropyran derivative (VII). The cleavage of the Tes protecting group by means of TsOH, followed by oxidation of the resulting alcohol with SO3/pyridine in DMSO/dichloromethane gives the aldehyde (VIII). A new olefination reaction of aldehyde (VIII) with phosphorane (IX) by means of NaH in THF yields the methoxyamide (X), which is reduced with DIBAL in THF to afford the unsaturated aldehyde (XI). Finally, this aldehyde is treated with (2R,4R)-pentanediol (XII) and montmorillonite K-10 in hot toluene to provide the target 1,3-dioxane intermediate (XIII).
| 【1】 Mulzer, J.; Hanbauer, M.; Total synthesis of the antitumor agent (-)-laulimalide. Tetrahedron Lett 2002, 43, 18, 3381. |
| 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) | 61198 | (2S)-2-hydroxycyclopentanone | C5H8O2 | 详情 | 详情 | |
| (II) | 61199 | (2S)-2-{[tert-butyl(diphenyl)silyl]oxy}cyclopentanone | C21H26O2Si | 详情 | 详情 | |
| (III) | 61200 | dipropyl methylphosphonate | C7H17O3P | 详情 | 详情 | |
| (IV) | 61201 | dipropyl (3S)-3-{[tert-butyl(diphenyl)silyl]oxy}-2-oxo-5-[(triethylsilyl)oxy]pentylphosphonate | C33H55O6PSi2 | 详情 | 详情 | |
| (V) | 61148 | (2S)-4-methyl-3,6-dihydro-2H-pyran-2-carbaldehyde | C7H10O2 | 详情 | 详情 | |
| (VI) | 61202 | (E,4S)-4-{[tert-butyl(diphenyl)silyl]oxy}-1-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-6-[(triethylsilyl)oxy]-1-hexen-3-one | C34H50O4Si2 | 详情 | 详情 | |
| (VII) | 61203 | (5S,6S)-6-{[tert-butyl(diphenyl)silyl]oxy}-10,10-diethyl-5-{(E)-2-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]ethenyl}-2,4,9-trioxa-10-siladodecane; tert-butyl(diphenyl)silyl (1S,2S,3E)-2-(methoxymethoxy)-4-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-1-{2-[(triethylsilyl)oxy]ethyl}-3-butenyl ether | C36H56O5Si2 | 详情 | 详情 | |
| (VIII) | 61204 | (3S,4S,5E)-3-{[tert-butyl(diphenyl)silyl]oxy}-4-(methoxymethoxy)-6-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-5-hexenal | C30H40O5Si | 详情 | 详情 | |
| (IX) | 61205 | dipropyl 2-[methoxy(methyl)amino]-2-oxoethylphosphonate | C10H22NO5P | 详情 | 详情 | |
| (X) | 61206 | (2E,5S,6S,7E)-5-{[tert-butyl(diphenyl)silyl]oxy}-N-methoxy-6-(methoxymethoxy)-N-methyl-8-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-2,7-octadienamide | C34H47NO6Si | 详情 | 详情 | |
| (XI) | 61154 | (2E,5S,6S,7E)-5-{[tert-butyl(diphenyl)silyl]oxy}-6-(methoxymethoxy)-8-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-2,7-octadienal | C32H42O5Si | 详情 | 详情 | |
| (XII) | 57935 | (2S,4S)-2,4-pentanediol | C5H12O2 | 详情 | 详情 | |
| (XIII) | 61155 | tert-butyl(diphenyl)silyl (1S,2S,3E)-1-{(E)-3-[(4R,6R)-4,6-dimethyl-1,3-dioxan-2-yl]-2-propenyl}-2-(methoxymethoxy)-4-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-3-butenyl ether; (5S,6S)-6-{(E)-3-[(4R,6R)-4,6-dimethyl-1,3-dioxan-2-yl]-2-propenyl}-9,9-dimethyl-5-{(E)-2-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]ethenyl}-8,8-diphenyl-2,4,7-trioxa-8-siladecane | C37H52O6Si | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(XVI)The intermediate phenyl sulfone (XXIII) has been obtained as follows. The reaction of tetrahydropyranyl glycidol (I) with isopropenyl bromide (X) by means of CuCN in THF gives the secondary alcohol (XI), which is treated with allyl bromide (XII) and KH in THF to yield the allyl ether (XIII). A ring closing metathesis reaction with (XIII) catalyzed by a Ru catalyst yields the protected dihydropyran derivative (XIV), which is treated with CSA in methanol to afford the carbinol (XV). The oxidation of (XV) with (COCl)2 and DMSO in dichloromethane provides the carbaldehyde (XVI), which is treated with CBr4 and PPh3 in dichloromethane to give the dibromovinyl derivative (XVII). The condensation of (XVII) with the intermediate aldehyde (VI) by means of BuLi in THF yields the propargyl alcohol derivative (XVIII), which is oxidized with DMP to the corresponding acetylenic ketone (XIX). Alternatively, acetylenic ketone (XIX) can also be obtained by condensation of dibromovinyl derivative (XVII) with the intermediate Weinreb amide (IX) by means of BuLi in THF. The enantioselective reduction of ketone (XIX) with L-Selectride in THF affords the chiral propargyl alcohol (XX), which is reduced with Red-Al and treated with TFA to provide the trans-allylic alcohol (XXI). The reaction of the diol (XXI) with Pmp-CH(OEt)2 and CSA gives the acetal (XXII), which is finally reduced with DIBAL in dichloromethane to yield the intermediate Pmb-protected phenyl sulfone (XXIII).
| 【1】 Ghosh, A.K.; Wang, Y.; Kim, J.T.; Total synthesis of microtubule-stabilizing agent (-)-laulimalide. J Org Chem 2001, 66, 26, 8973. |
| 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) | 63105 | 2-[(2R)oxiranyloxy]tetrahydro-2H-pyran; (2R)oxiranyl tetrahydro-2H-pyran-2-yl ether | C7H12O3 | 详情 | 详情 | |
| (VI) | 63109 | (2S)-2-[(4-methoxybenzyl)oxy]-4-(phenylsulfonyl)butanal | C18H20O5S | 详情 | 详情 | |
| (IX) | 63111 | (2S)-N-methoxy-2-[(4-methoxybenzyl)oxy]-N-methyl-4-(phenylsulfonyl)butanamide | C20H25NO6S | 详情 | 详情 | |
| (X) | 42375 | 2-bromo-1-propene；2-bromopropene;Isopropenyl bromide;a-Methylvinyl bromide | 557-93-7 | C3H5Br | 详情 | 详情 |
| (XI) | 63112 | (2S)-4-methyl-1-(tetrahydro-2H-pyran-2-yloxy)-4-penten-2-ol | C11H20O3 | 详情 | 详情 | |
| (XII) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (XIII) | 63113 | allyl (1S)-3-methyl-1-[(tetrahydro-2H-pyran-2-yloxy)methyl]-3-butenyl ether; 2-{[(2S)-2-(allyloxy)-4-methyl-4-pentenyl]oxy}tetrahydro-2H-pyran | C14H24O3 | 详情 | 详情 | |
| (XIV) | 63114 | 2-{[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]methoxy}tetrahydro-2H-pyran; [(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]methyl tetrahydro-2H-pyran-2-yl ether | C12H20O3 | 详情 | 详情 | |
| (XV) | 61173 | [(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]methanol | C7H12O2 | 详情 | 详情 | |
| (XVI) | 61148 | (2S)-4-methyl-3,6-dihydro-2H-pyran-2-carbaldehyde | C7H10O2 | 详情 | 详情 | |
| (XVII) | 63115 | (2S)-2-(2,2-dibromovinyl)-4-methyl-3,6-dihydro-2H-pyran | C8H10Br2O | 详情 | 详情 | |
| (XVIII) | 63116 | (4S)-4-[(4-methoxybenzyl)oxy]-1-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-6-(phenylsulfonyl)-1-hexyn-3-ol | C26H30O6S | 详情 | 详情 | |
| (XIX) | 63117 | (4S)-4-[(4-methoxybenzyl)oxy]-1-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-6-(phenylsulfonyl)-1-hexyn-3-one | C26H28O6S | 详情 | 详情 | |
| (XX) | 63118 | (3S,4S)-4-[(4-methoxybenzyl)oxy]-1-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-6-(phenylsulfonyl)-1-hexyn-3-ol | C26H30O6S | 详情 | 详情 | |
| (XXI) | 63119 | (E,3S,4S)-1-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-6-(phenylsulfonyl)-1-hexene-3,4-diol | C18H24O5S | 详情 | 详情 | |
| (XXII) | 63120 | 2-((4S,5S)-2-(4-methoxyphenyl)-5-{(E)-2-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]ethenyl}-1,3-dioxolan-4-yl)ethyl phenyl sulfone; (2S)-2-((E)-2-{(4S,5S)-2-(4-methoxyphenyl)-5-[2-(phenylsulfonyl)ethyl]-1,3-dioxolan-4-yl}ethenyl)-4-methyl-3,6-dihydro-2H-pyran | C26H30O6S | 详情 | 详情 | |
| (XXIII) | 63121 | (3S,4S,5E)-4-[(4-methoxybenzyl)oxy]-6-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-1-(phenylsulfonyl)-5-hexen-3-ol | C26H32O6S | 详情 | 详情 |