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【结 构 式】 
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【分子编号】37649 【品名】 【CA登记号】 |
【 分 子 式 】C22H30O8 【 分 子 量 】422.4754 【元素组成】C 62.55% H 7.16% O 30.3% |
合成路线1
该中间体在本合成路线中的序号：(XIX)The reaction of ethyl 3-(3-furyl)acrylate (I) with the cuprate t-Bu2CuCNLi2, followed by reduction with diisobutylaluminum hydride gives the tert-butylated aldehyde (II), which is condensed with ethynylmagnesium bromide (III), yielding a mixture of the syn and anti acetylenic alcohols (IV) and (V). After chromatographic separation, the undesired anti-alcohol (IV) is converted to the syn-alcohol (V) by a Mitsunobu inversion. Alcohol (V) was protected as the triethylsilyl ether and carboxylated with ethyl chloroformate affording the acetylenic ester (VI), which is cyclized with the zinc/copper enolate (VII) giving the 2-oxocyclopentenecarboxylate (VIII). The photocyclization of (VIII) with U.V. light (366 nm) yields the tetracyclic ester (IX), which is desilylated with HF and mesylated with mesyl chloride affording mesylate (X). Lactonization of (X) with PPTS gives the pentacyclic lactone (XI), which is dehydrogenated with PhSeCl and NaIO4 to the enone (XII). The opening of the cyclobutane ring of (XII) with dimethyldioxirane (DMDO) and TsOH yields the trihydroxy compound (XIII), which is treated with MeOH and TsOH to afford the bis(methyl)acetal (XIV). The deoxygenation of (XIV) through the corresponding xanthate and reduction with tributylstannane gives intermediate (XV), which is hydroxylated and acylated yielding the propionyl ester (XVI). Cyclization of (XVI) by means of LDA in THF followed by treatment with NaOMe affords a diastereomeric mixture (XVII), which is separated by chromatography. The isolated epimer (XVIII) was treated with MeOH and camphorsulfonic acid (CSA) resulting in the methanolysis of its lactone ring and formation of a new tetrahydrofuran ring providing the pentacyclic compound (XIX).
| 【1】 Crimmins, M.T.; et al.; The total synthesis of (±)-ginkgolide B. J Am Chem Soc 2000, 122, 35, 8453. |
| 【2】 Pace, J.M.; Watterson, S.H.; Nantermet, P.G.; Crimmins, M.T.; Kim-Meade, A.S.; Wagman, A.S.; Thomas, J.B.; Total synthesis of (±)-ginkgolide B. J Am Chem Soc 1999, 121, 43, 10249. |
| 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) | 37633 | ethyl (E)-3-(3-furyl)-2-propenoate | C9H10O3 | 详情 | 详情 | |
| (II) | 37634 | 3-(3-furyl)-4,4-dimethylpentanal | C11H16O2 | 详情 | 详情 | |
| (III) | 17778 | ETHYNYLMAGNESIUM BROMIDE; bromo(ethynyl)magnesium | 4301-14-8 | C2HBrMg | 详情 | 详情 |
| (IV) | 37635 | (3R,5S)-5-(3-furyl)-6,6-dimethyl-1-heptyn-3-ol | C13H18O2 | 详情 | 详情 | |
| (V) | 37636 | (3S,5S)-5-(3-furyl)-6,6-dimethyl-1-heptyn-3-ol | C13H18O2 | 详情 | 详情 | |
| (VI) | 37637 | ethyl (4S,6S)-6-(3-furyl)-7,7-dimethyl-4-[(triethylsilyl)oxy]-2-octynoate | C22H36O4Si | 详情 | 详情 | |
| (VIII) | 37638 | ethyl 2-[(1S,3S)-3-(3-furyl)-4,4-dimethyl-1-[(triethylsilyl)oxy]pentyl]-5-oxo-1-cyclopentene-1-carboxylate | C25H40O5Si | 详情 | 详情 | |
| (IX) | 37639 | ethyl (1S,3S,6aR)-3-(tert-butyl)-7-oxo-1-[(triethylsilyl)oxy]-2,3,8,9-tetrahydro-1H,6aH-dicyclopenta[2,3:3,4]cyclobuta[1,2-b]furan-6b(7H)-carboxylate | C25H40O5Si | 详情 | 详情 | |
| (X) | 37640 | ethyl (1S,3S,6aR)-3-(tert-butyl)-1-[(methylsulfonyl)oxy]-7-oxo-2,3,8,9-tetrahydro-1H,6aH-dicyclopenta[2,3:3,4]cyclobuta[1,2-b]furan-6b(7H)-carboxylate | C20H28O7S | 详情 | 详情 | |
| (XI) | 37641 | C17H20O4 | 详情 | 详情 | ||
| (XII) | 37642 | C17H18O4 | 详情 | 详情 | ||
| (XIII) | 37643 | C17H22O7 | 详情 | 详情 | ||
| (XIV) | 37644 | C19H26O7 | 详情 | 详情 | ||
| (XV) | 37645 | C19H26O6 | 详情 | 详情 | ||
| (XVI) | 37646 | C22H30O8 | 详情 | 详情 | ||
| (XVII) | 37647 | C22H30O8 | 详情 | 详情 | ||
| (XVIII) | 37648 | C22H30O8 | 详情 | 详情 | ||
| (XIX) | 37649 | C22H30O8 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XIX)Elimination of methanol from (XIX) by means of PPTS and pyridine in hot chlorobenzene gives the diunsaturated pentacyclic compound (XX), which by cyclization with tert-butyl hydroperoxide and vanadyl acetylacetonate yields the hexacyclic compound (XXI). Finally, the double bond of (XXI) is treated first with dimethyldioxirane (DMDO) yielding the epoxide intermediate (XXII) that is then opened and oxidized with Br2, and NaOAc in AcOH.
| 【1】 Crimmins, M.T.; et al.; The total synthesis of (±)-ginkgolide B. J Am Chem Soc 2000, 122, 35, 8453. |
| 【2】 Pace, J.M.; Watterson, S.H.; Nantermet, P.G.; Crimmins, M.T.; Kim-Meade, A.S.; Wagman, A.S.; Thomas, J.B.; Total synthesis of (±)-ginkgolide B. J Am Chem Soc 1999, 121, 43, 10249. |