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Asymmetric total synthesis method for mulinane type diterpenoids and analogues thereof

A juniperane, asymmetric technology, applied in the field of asymmetric total synthesis, can solve the problems of long synthesis route and low total yield, etc.

Inactive Publication Date: 2019-02-26
NANKAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But the synthetic route is longer, and the total yield is also lower

Method used

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  • Asymmetric total synthesis method for mulinane type diterpenoids and analogues thereof
  • Asymmetric total synthesis method for mulinane type diterpenoids and analogues thereof
  • Asymmetric total synthesis method for mulinane type diterpenoids and analogues thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041]

[0042] Weigh the catalyst Ir-(R)-SpiroPAP (20 mg, 0.2 mmol) and potassium tert-butoxide (560 mg, 5 mmol) in the glove box into two dry 25 mL Schlenk tubes. Anhydrous ethanol (10 mL) was added to the Schlenk tube to dissolve the solid compound. After weighing out the hydrogenation substrate (10.0g, 50mmol) in the 250mL hydrogenation reaction inner tube, put the reaction inner tube into the hydrogenation reactor, and replace the system with nitrogen, and use a syringe to quickly add to the hydrogenation inner tube Add absolute ethanol (60 mL), catalyst solution and alkali solution, quickly replace the system with hydrogen atmosphere and fill with hydrogen to 50 atm, and stir the reaction at room temperature (25°C) until there is no hydrogen pressure drop. Slowly release hydrogen, add saturated ammonium chloride (30 mL) to the system, stand in a separatory funnel to separate the layers, extract the aqueous layer with ethyl acetate (50 mL×3), combine the organic phases, an...

Embodiment 2

[0044]

[0045] Into a 250mL three-necked round bottom flask equipped with a magnetic stirrer, add the raw materials (2.0g, 10mmol), add 100mL of dichloromethane to dissolve it, then add 6g of diatomaceous earth, then add PCC (6.5g, 30mmol), and react at room temperature 16h, monitored by TLC. After the reaction, it was filtered through diatomaceous earth to remove the solution. Column chromatography on a silica gel column (PE:EA=4:1) yielded 1.8 g of product as a pale yellow liquid. The yield was 92%, R f =0.5 (PE:EA=4:1). 92% yield, 1 H NMR(400MHz, CDCl 3 ) δ 4.19 (dd, J = 7.1, 2.3 Hz, 2H), 2.88 (d, J = 11.6 Hz, 1H), 2.39 (d, J = 8.5 Hz, 3H), 2.23-2.12 (m, 1H), 1.63 (dd, J = 14.1, 6.9 Hz, 1H), 1.47 (dd, J = 12.0, 9.0 Hz, 1H), 1.26 (t, J = 7.1 Hz, 3H), 0.93 (dd, J = 14.7, 6.7 Hz , 6H). 13 CNMR(101MHz, CDCl 3 )δ170.4, 61.4, 60.5, 48.3, 38.9, 32.9, 25.4, 20.9, 20.0, 14.3.

Embodiment 3

[0047]

[0048] Raw material 3 (1.4 g, 7 mmol) was added to a 250 mL three-necked round bottom flask equipped with a magnetic stir bar, and 45 mL of anhydrous acetonitrile was added to dissolve it. Add cesium carbonate (6.8g, 21mmol), and react at room temperature for 30min. Then add iodide 4 (2.8g, 11mmol), raise to 60°C and react overnight, add iodide 4 (1.4g, 5.5mmol) after 24h, and continue the reaction. TLC monitoring, after the completion of the reaction, filtered through diatomaceous earth, the resulting solution was desolventized, the residue was dissolved in water, extracted with ethyl acetate, the organic phases were combined, and dried over anhydrous magnesium sulfate. Suction filtration, desolventization, column chromatography on silica gel column (PE:EA=8:1), to obtain 1.5g product, which is a pale yellow liquid, the yield is 65%, R f =0.5 (PE:EA=4:1). 1 H NMR(400MHz, CDCl 3 )δ7.19(dd, J=8.9, 7.6Hz, 1H), 6.79-6.71(m, 3H), 4.14(dd, J=7.1, 4.5Hz, 2H), 3.79(s, 3H), 2...

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Abstract

The invention relates to an asymmetric total synthesis method for mulinane type diterpenoid natural products and analogues thereof. The method includes taking 3-isopropyl-2-ethoxycarbonyl cyclopentenone as an initial raw material; preparing optically pure chiral alcohol under the action of an iridium catalyst of a chiral spiropyridine aminophosphine ligand through an asymmetric catalytic hydrogenation method, and oxidizing the chiral alcohol into beta-keto ester; constructing a quaternary carbon center through alkylation reaction, and constructing a tricyclic system through intramolecular Friedel-Crafts reaction; and constructing a 5-6-7 tricyclic basic skeleton through Birch reduction, 1,4-conjugate addition, re-carburization and ring enlargement reaction and other reaction steps. The constructing of a carbon skeleton can be accomplished through 1,2-addition, concise and efficient asymmetric total synthesis of mulinane type diterpenoid natural products and analogues thereof can be accomplished through later transformation and modification of functional groups.

Description

Technical field [0001] The invention relates to a method for asymmetric total synthesis of Mulinane type diterpenoid natural products and their analogs, and belongs to the field of organic synthesis. Background technique [0002] The Mulinane type terpenoid natural product is a diterpene compound with a 5-6-7 tricyclic system. The natural products of this kind of diterpenoids are secondary metabolites isolated from Umbelliferae plants such as Azorella, Bolax and Mulinum in the Andean flora. These Umbelliferae plants are used by the locals to treat diabetes, bronchitis, gastrointestinal discomfort and other diseases. In 1990, Loyola et al. isolated this type of diterpenoids for the first time from Mulinum crassifolium (Loyola, L.A.; et al. Tetrahedron 1990, 46, 5413; Phytochemistry 1990, 29, 3950). So far, more than 30 members of this family have been isolated (ISMarcos, RFMoro, A. Gil-Mesón, D. Díez, in Studies in natural products chemistry, Atta-ur-Rahman, Ed. Elsevier, Amster...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C69/145C07C67/08C07C67/31C07C67/313C07C67/343C07C67/333C07C67/303C07C67/307C07C67/317C07C69/757C07C51/09C07C51/367C07C62/32C07C51/377C07C61/29C07D493/08C07D493/04C07C29/147C07C35/37C07C29/60C07C33/16C07B53/00
CPCC07B53/00C07C29/147C07C29/60C07C51/09C07C51/367C07C51/377C07C67/08C07C67/303C07C67/307C07C67/31C07C67/313C07C67/317C07C67/333C07C67/343C07D493/04C07D493/08C07B2200/07
Inventor 谢建华刘运亭王立新
Owner NANKAI UNIV
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