RESUMO
The enantiomeric separation of a racemate of 7-oxa-bicyclo[2.2.1]heptene sulfonate (OBHS) derivatives, a Selective Estrogen Receptor Modulator (SERM), was obtained using supercritical fluid chromatography in tandem with UV and mass spectrometry (SFC/UV and SFC/MS, respectively). Supercritical CO2 modified with methanol or isopropyl alcohol was used with isopropylamine (IPAm), trimethylamine (TEA), or trifluoroacetic acid (TFA) as an additive to obtain the enantiomers separations. Both Chiralpak IC and IA were evaluated for the separation of enantiomers. Results showed enantiomers separation can be achieved in less than 5â¯min with a resolution greater than 1 and 0.9, respectively, for the different OBHS derivatives (compounds A and B) using supercritical CO2 modified with 40% isopropyl alcohol containing 0.25% IPAm and IC column applying isocratic conditions. Similar conditions were used with the semi-preparative Chiralpak IC column to isolate more than 50â¯mg of each enantiomer. SFC/MS and SFC/UV results showed pure enantiomers were isolated. Method development via SFC was much simpler than those reported in the literature using HPLC.
Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/análise , Compostos Bicíclicos Heterocíclicos com Pontes/isolamento & purificação , Cromatografia com Fluido Supercrítico/métodos , Moduladores Seletivos de Receptor Estrogênico/análise , Moduladores Seletivos de Receptor Estrogênico/isolamento & purificação , 2-Propanol , Compostos Bicíclicos Heterocíclicos com Pontes/química , Espectrometria de Massas , Metanol , Moduladores Seletivos de Receptor Estrogênico/química , Espectrofotometria Ultravioleta , EstereoisomerismoRESUMO
Herein, we report for the first time the design and linear synthesis of a truncated calyculone H (7) that lacks the telltale isopropyl/isopropylene groups, whereas the 12-membered macrocycle remains intact. Key steps for the framework of target molecule include allylic oxidation using SeO2, Sharpless asymmetric epoxidation, Barbier zinc allylation, and ring-closing metathesis (RCM) reactions. A second truncated "calyculone-like" analogue, 27, with a different oxidation pattern around the ring was also synthesized following a similar strategy. Screening for in vitro cytotoxicity against a panel of 60 human cancer cell lines revealed that 7 was as potent if not more so (for a few cell lines) than the natural product calyculone A (2).
RESUMO
The first stereoselective synthesis of (Z)-cryptomoscatone D2, a naturally occurring G(2) checkpoint inhibitor, was accomplished using propane-1,3-diol as the starting material. The Maruoka asymmetric allylation, ring closing metathesis and the hydrogenation of the triple bond employing Lindlar's catalyst were involved as the key steps.
Assuntos
Antineoplásicos Fitogênicos/síntese química , Lactonas/síntese química , Propilenoglicóis/química , Antineoplásicos Fitogênicos/farmacologia , Catálise , Linhagem Celular Tumoral , Cryptocarya/química , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Hidrogenação , Lactonas/farmacologia , Estrutura Molecular , EstereoisomerismoRESUMO
Treatment of N-tosylaldimines with acetophenone at room temperature in the presence of BF(3).OEt(2) as a catalyst furnished the corresponding N-tosyl beta-amino ketones in high yields (77-86%) within 6-9 h. Subsequent reduction and cyclization of these compounds afforded 2,4-disubstituted N-tosylazetidines, comprising a three-step, high-yielding synthesis starting from aldimines.
Assuntos
Acetofenonas/química , Azetidinas/síntese química , Iminas/química , Cetonas/química , Compostos de Tosil/química , Aminação , Azetidinas/química , Compostos de Bromo/química , Catálise , Ciclização , Éter/química , Compostos de Flúor/química , Cetonas/síntese química , Modelos Químicos , Oxirredução , Temperatura , Fatores de Tempo , Compostos de Tosil/síntese químicaRESUMO
Treatment of N-tosyl aldimines with dialkyl trimethylsilyl phosphites at 0 degrees C in the presence of iodine as a catalyst afforded the corresponding sulfonamide phosphonates in excellent yields within 1.5 to 2.5 h.