Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F21%3A10438546" target="_blank" >RIV/00216208:11160/21:10438546 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=1W0vecEm9X" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=1W0vecEm9X</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3762/bjoc.17.188" target="_blank" >10.3762/bjoc.17.188</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

Popis výsledku v původním jazyce

A new highly diastereoselective synthesis of the polyhydroxylated pyrrolidine alkaloid (+/-)-codonopsinol B and its N-nor-methyl analogue, starting from achiral materials, is presented. The strategy relies on the trans-stereoselective epoxidation of 2,3-dihydroisoxazole with in situ-generated DMDO, the syn-selective alpha-chelation-controlled addition of vinyl-MgBr/CeCl3 to the isoxazolidine-4,5-diol intermediate, and the substrate-directed epoxidation of the terminal double bond of the corresponding gamma-amino-alpha,beta-diol with aqueous hydrogen peroxide catalyzed by phosphotungstic heteropoly acid. Each of the key reactions proceeded with an excellent diastereoselectivity (dr &gt; 95:5). (+/-)-Codonopsinol B was prepared in 10 steps with overall 8.4% yield. The antiproliferative effect of (+/-)-codonopsinol B and its N-nor-methyl analogue was evaluated using several cell line models.

Název v anglickém jazyce

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

Popis výsledku anglicky

A new highly diastereoselective synthesis of the polyhydroxylated pyrrolidine alkaloid (+/-)-codonopsinol B and its N-nor-methyl analogue, starting from achiral materials, is presented. The strategy relies on the trans-stereoselective epoxidation of 2,3-dihydroisoxazole with in situ-generated DMDO, the syn-selective alpha-chelation-controlled addition of vinyl-MgBr/CeCl3 to the isoxazolidine-4,5-diol intermediate, and the substrate-directed epoxidation of the terminal double bond of the corresponding gamma-amino-alpha,beta-diol with aqueous hydrogen peroxide catalyzed by phosphotungstic heteropoly acid. Each of the key reactions proceeded with an excellent diastereoselectivity (dr &gt; 95:5). (+/-)-Codonopsinol B was prepared in 10 steps with overall 8.4% yield. The antiproliferative effect of (+/-)-codonopsinol B and its N-nor-methyl analogue was evaluated using several cell line models.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Beilstein Journal of Organic Chemistry

ISSN

1860-5397

e-ISSN

—

Svazek periodika

17

Číslo periodika v rámci svazku

November

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

6

Strana od-do

2781-2786

Kód UT WoS článku

000722951500001

EID výsledku v databázi Scopus

2-s2.0-85122371537