Method for synthesizing novel tetracyclic diterpene compound from stevioside

A technology for tetracyclic diterpenoids and compounds, which is applied in the field of synthesizing novel tetracyclic diterpenoids from stevioside, and can solve the problem of less research on structural synthesis

Inactive Publication Date: 2011-06-01
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Research on the extraction, separation, and structure identification of such compounds is currently very active, but there are relatively few studies on structural synthesis.

Method used

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  • Method for synthesizing novel tetracyclic diterpene compound from stevioside
  • Method for synthesizing novel tetracyclic diterpene compound from stevioside
  • Method for synthesizing novel tetracyclic diterpene compound from stevioside

Examples

Experimental program
Comparison scheme
Effect test

specific example 2

[0062] En-13,15-dihydroxykaurene-19-acid (15-hydroxysteviol) (I-a)

[0063] 0.48g SeO 2 , 1.76 mL t-BuOOH was dissolved in 45 mL THF. After stirring for a while, 2.00 g of steviol (I-1) dissolved in 50 mL of THF was added. Reaction at room temperature for 20h. Saturated brine dissolved with a small amount of sodium bisulfite was added to the reaction system, extracted with ethyl acetate, and the extract was washed with saturated brine. After concentrating the extract, the crude product can be directly dropped into the next step reaction. If purification is required, column chromatography (ethyl acetate:petroleum ether (V / V)=2.5:1 and the addition of acetic acid with a volume of 0.3% of the total volume of acetic acid and petroleum ether) can give 1.25g of pure white solid. 59.5%. ESI-MS: 333 [M-H] - .

specific example 3

[0065] En-13-Hydroxy-15-carbonylkaurene-19-acid (15-carbonyl steviol) (I-1)

[0066] 0.50g 15-hydroxysteviol (I-a), 0.80g PDC were dissolved in 2mL DMF. React overnight at room temperature. Add saturated brine to the reaction system, extract with ethyl acetate, wash the extract with saturated brine, and dry over anhydrous sodium sulfate. After concentrating the extract, the crude product was subjected to column chromatography (ethyl acetate:petroleum ether (V / V)=1:1 and 0.3% acetic acid was added to the total volume of ethyl acetate and petroleum ether). Obtained 0.36 g of pure white solid, yield: 71.5%. m.p.236-238°C.

[0067] IR(KBr)v cm -1 : 3511, 3457, 3419, 2997, 2946, 2865, 1692, 1648, 1459, 1396, 1338, 1242, 1189, 1156, 1095, 1046. 1 H NMR (400MHz, DMSO-d 6 , δ, ppm): 11.99 (s, 1H, -COOH), 5.82 (s, 1H, 17-H), 5.35 (s, 1H, 17-H), 2.32 (d, 1H J=12Hz, 14-Hα ), 1.14(s, 3H, 18-C H 3 ), 0.95(s, 3H, 20-C H 3 ).ES1-MS: 331[M-H] - .

[0068] Wherein PDC is prepared ...

specific example 4

[0070] En-13-Hydroxy-15-Carbonyl-Kurene-19-n-Propionamide (I-2)

[0071] Dissolve 0.500g of 15-hydroxy steviol (I-a) in 10mL of anhydrous THF and 3mL of anhydrous DMF, add 0.402g of DCC, 0.298g, HoBt, stir at room temperature for 2h, then add 0.432mL of n-propylamine. Heated to reflux for 8h. The reaction solution was left to cool and then filtered, 50 mL of water was added to the filtrate, extracted twice with 30 mL of ethyl acetate, the extracts were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated to obtain the crude product enantio-13,15 - Dihydroxykaurene-19-propionamide 0.510 g.

[0072] Dissolve the above crude product in 6 mL of DMF, add 0.78 g of PDC, react at room temperature for 12 hours, add the reaction solution to 30 ml of water, extract three times with 20 ml of ethyl acetate, combine the extracts, wash with saturated saline and evaporate the solvent to obtain enantio-13-hydroxy 0.49 g of the crude prod...

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Abstract

The invention discloses a method for synthesizing a novel tetracyclic diterpene compound from stevioside, which is cost-efficient and feasible. The compound is represented by a general formula (I), wherein the definitions of R1, R2, X, Y are shown in the specification. The invention discloses a potential application value of the compound in the aspects of anti-tumor and anti-inflammation and a detailed preparation method of the compound as well as physical data of Fourier transform infrared spectroscopy (FT-IR), hydrogen nuclear magnetic resonance spectroscopy (1 HNMR), mass spectrometry (MS) and the like.

Description

Technical field: [0001] The invention relates to a cheap, easy-to-obtain, economically applicable method for synthesizing novel tetracyclic diterpenoids from steviosides and the application of a drug combination with such compounds as active ingredients in anti-tumor and anti-inflammation aspects. Background technique: [0002] Cancer is a kind of disease that seriously threatens human health. Searching for highly effective and low-toxic anticancer compounds from natural products has always been an important aspect of anticancer drug development. Among them, diterpenoids have received extensive attention because of their unique pharmacological effects, and some have become drugs on the market, such as paclitaxel, salvia miltiorrhiza, oridonin, etc. Tetracyclic diterpenoids are cyclic diterpenoids synthesized from geranylgeranyl pyrophosphate (GGPP) through an acid-catalyzed pathway, including kaurane diterpenes and bayonets Diterpenes, etc. Research on the extraction, sepa...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C62/32C07C62/38C07C51/09C07C51/377C07C51/367C07C51/373C07C235/82C07C231/12C07D295/088C07C69/757C07C67/10C07C69/145C07C67/08C07C35/44C07C29/147C07C69/16C07C69/18C07C67/29C07C49/743C07C45/65C07C309/73C07C303/28C07C67/327C07C69/753C07C67/317C07C67/31C07C67/313A61K31/19A61K31/191A61K31/16A61K31/4453A61K31/215A61K31/22A61K31/047A61K31/122A61K31/255A61P35/00A61P29/00
Inventor 张大永吴晓明李景汤湧王可
Owner CHINA PHARM UNIV
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