|
【结 构 式】 
|
【分子编号】20188 【品名】ethyl (2E,6E)-9-[(4R,5S)-5-decyl-2,2-dimethyl-1,3-dioxolan-4-yl]-2,6-nonadienoate 【CA登记号】 |
【 分 子 式 】C26H46O4 【 分 子 量 】422.64884 【元素组成】C 73.89% H 10.97% O 15.14% |
合成路线1
该中间体在本合成路线中的序号：(XIV)1) The reaction of undecanal (I) with vinylmagnesium bromide (II) in THF gives 1-tridecen-3-ol (III), which is condensed with propionic acid (IV) by means of triethyl orthoacetate in refluxing xylene yielding 4(E)-pentadecenoic acid ethyl ester (V). The reaction of (V) with AD-mix-beta and methanesulfonamide in tert-butanol affords (R,R)-5-(1-hydroxyundecyl)tetrahydrofuran-2-one (VI), which by reaction with p-nitrobenzoic acid and triphenylphosphine in benzene gives the corresponding ester (VII). The reaction of (VII) first with LiAlH4 in ether, followed by a treatment with acetone and p-toluenesulfonic acid yields the acetonide (VIII), which by oxidation of its primary alcohol with pyridinium chlorochromate (PCC) in dichloromethane affords the corresponding aldehyde (IX). The reaction of (IX) with vinylmagnesium bromide (II) in ether gives the allyl alcohol (X), which by condensation with proionic acid (IV) and triethyl orthoacetate yields (4E,8R,9S)-8,9-(isopropylidenedioxy)-4-nonadecenoic acid ethyl ester (XI), The reduction of (XI) with diisobutylaluminum hydride (DIBAL) in toluene affords the corresponding aldehyde (XII), which is condensed with triethyl phosphonoacetate (XIII) by means of NaH in toluene giving (2E,6E,10R,11S)-10,11-(isopropylidenedioxy)-heneicosa-2,6-dienoic acid ethyl ester (XIV).
| 【1】 Yazbak, A.; et al.; Total synthesis of uvaricin. J Org Chem 1998, 63, 17, 5863. |
| 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) | 20175 | undecanal | 112-44-7 | C11H22O | 详情 | 详情 |
| (II) | 10386 | Allyl(bromo)magnesium | 1730-25-2 | C3H5BrMg | 详情 | 详情 |
| (III) | 20177 | 1-tridecen-3-ol | C13H26O | 详情 | 详情 | |
| (IV) | 20178 | propionic acid | 79-09-4 | C3H6O2 | 详情 | 详情 |
| (V) | 20179 | ethyl (E)-4-pentadecenoate | C17H32O2 | 详情 | 详情 | |
| (VI) | 20180 | (5R)-5-[(1R)-1-hydroxyundecyl]dihydro-2(3H)-furanone | C15H28O3 | 详情 | 详情 | |
| (VII) | 20181 | (1R)-1-[(2S)-4-oxo-1,3-dioxolan-2-yl]undecyl 4-nitrobenzoate | C21H29NO7 | 详情 | 详情 | |
| (VIII) | 20182 | 3-[(4R,5S)-5-decyl-2,2-dimethyl-1,3-dioxolan-4-yl]-1-propanol | C18H36O3 | 详情 | 详情 | |
| (IX) | 20183 | 3-[(4R,5S)-5-decyl-2,2-dimethyl-1,3-dioxolan-4-yl]propanal | C18H34O3 | 详情 | 详情 | |
| (X) | 20184 | (3S)-5-[(4R,5S)-5-decyl-2,2-dimethyl-1,3-dioxolan-4-yl]-1-penten-3-ol | C20H38O3 | 详情 | 详情 | |
| (XI) | 20185 | ethyl (E)-7-[(4R,5S)-5-decyl-2,2-dimethyl-1,3-dioxolan-4-yl]-4-heptenoate | C24H44O4 | 详情 | 详情 | |
| (XII) | 20186 | (E)-7-[(4R,5S)-5-decyl-2,2-dimethyl-1,3-dioxolan-4-yl]-4-heptenal | C22H40O3 | 详情 | 详情 | |
| (XIII) | 10019 | Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate | 867-13-0 | C8H17O5P | 详情 | 详情 |
| (XIV) | 20188 | ethyl (2E,6E)-9-[(4R,5S)-5-decyl-2,2-dimethyl-1,3-dioxolan-4-yl]-2,6-nonadienoate | C26H46O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XIV)2) The reduction of (XIV) with DIBAL followed by protection with methoxymethyl chloride (MOM-Cl) yields the methoxymethyl ether (XV), which by regioselective dihydroxylation with AD-mix-beta, followed by mesylation with mesyl chloride affords the dimesylate (XVI). A new regioselective dihydroxylation of (XVI) with AD-mix-beta gives the diol (XVII), which is cyclized by treatment first with p-toluenesulfonic acid and then by heating at 140 C in pyridine yielding the bis(tetrahydrofuran) derivative (XVIII). The deprotection of (XVIII) with boron trilfuoride.ethearate, followed by tosylation with tosyl chloride in pyridine affords the tosylate (XIX), which is cyclized to the epoxide (XX) by reaction with K2CO3 in methanol. The acetylation of the secondary alcohol of (XIX) with acetic anhydride in pyridine affords the acetate (XXI), which is condensed with trimethylsilylacetylene (XXII) by means of n-BuLi in THF giving the acetylenic alcohol (XXIII).
| 【1】 Yazbak, A.; et al.; Total synthesis of uvaricin. J Org Chem 1998, 63, 17, 5863. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIV) | 20188 | ethyl (2E,6E)-9-[(4R,5S)-5-decyl-2,2-dimethyl-1,3-dioxolan-4-yl]-2,6-nonadienoate | C26H46O4 | 详情 | 详情 | |
| (XV) | 20190 | (2E,6E)-9-[(4R,5S)-5-decyl-2,2-dimethyl-1,3-dioxolan-4-yl]-2,6-nonadienyl methoxymethyl ether; (4S,5R)-4-decyl-5-[(3E,7E)-9-(methoxymethoxy)-3,7-nonadienyl]-2,2-dimethyl-1,3-dioxolane | C26H48O4 | 详情 | 详情 | |
| (XVI) | 20191 | (4S,5R)-4-decyl-5-((3S,4S,7E)-9-(methoxymethoxy)-3,4-bis[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-7-nonenyl)-2,2-dimethyl-1,3-dioxolane; (E,6S,7S)-9-[(4R,5S)-5-decyl-2,2-dimethyl-1,3-dioxolan-4-yl]-6,7-bis[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-2-nonenyl methoxymethyl ether | C32H62O6S2 | 详情 | 详情 | |
| (XVII) | 20192 | (4S,5S,8R,9R)-4-[2-[(4R,5S)-5-decyl-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl]-2-methyl-5-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-2-methylene-3,11,13-trioxa-2lambda(6)-thia-1-tetradecene-8,9-diol | C32H64O8S2 | 详情 | 详情 | |
| (XVIII) | 20193 | 1(S)-[5(R)-[5(R)-[1(R)-Hydroxy-2-(methoxymethoxy)ethyl]tetrahydrofuran-2(R)-yl]tetrahydrofuran-2(R)-yl]undecan-1-ol | C23H44O6 | 详情 | 详情 | |
| (XIX) | 20194 | 1(S)-[5(R)-[5(R)-[1(R)-Hydroxy-2-(p-toluenesulfonyloxy)ethyl]tetrahydrofuran-2(R)-yl]tetrahydrofuran-2(R)-yl]undecan-1-ol | C28H46O7S | 详情 | 详情 | |
| (XX) | 20195 | 1(S)-[5(R)-[5(R)-(1(R),2-Epoxyethyl)tetrahydrofuran-2(R)-yl]tetrahydrofuran-2(R)-yl]undecan-1-ol | C21H38O4 | 详情 | 详情 | |
| (XXI) | 20196 | Acetic acid 1(S)-[5(R)-[5(R)-(1(R),2-Epoxyethyl)tetrahydrofuran-2(R)-yl]tetrahydrofuran-2(R)-yl]undecyl ester | C23H40O5 | 详情 | 详情 | |
| (XXII) | 23897 | ethynyl(trimethyl)silane；trimethylsilyl acetylene | 1066-54-2 | C5H10Si | 详情 | 详情 |
| (XXIII) | 20198 | Acetic acid 1(S)-[5(R)-[5(R)-(1(R)-hydoxy-3-butynyl)tetrahydrofuran-2(R)-yl]tetrahydrofuran-2(R)-yl]undecyl ester | C25H42O5 | 详情 | 详情 | |
| (XXIV) | 20205 | (5S)-3-[(E)-9-iodo-8-nonenyl]-5-methyl-3-(phenylsulfanyl)dihydro-2(3H)-furanone | C20H27IO2S | 详情 | 详情 |