ABSTRACT
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.
Subject(s)
Bridged Bicyclo Compounds, Heterocyclic/analysis , Bridged Bicyclo Compounds, Heterocyclic/isolation & purification , Chromatography, Supercritical Fluid/methods , Selective Estrogen Receptor Modulators/analysis , Selective Estrogen Receptor Modulators/isolation & purification , 2-Propanol , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Mass Spectrometry , Methanol , Selective Estrogen Receptor Modulators/chemistry , Spectrophotometry, Ultraviolet , StereoisomerismABSTRACT
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).
ABSTRACT
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.
Subject(s)
Antineoplastic Agents, Phytogenic/chemical synthesis , Lactones/chemical synthesis , Propylene Glycols/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Catalysis , Cell Line, Tumor , Cryptocarya/chemistry , G2 Phase Cell Cycle Checkpoints/drug effects , Humans , Hydrogenation , Lactones/pharmacology , Molecular Structure , StereoisomerismABSTRACT
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.
Subject(s)
Acetophenones/chemistry , Azetidines/chemical synthesis , Imines/chemistry , Ketones/chemistry , Tosyl Compounds/chemistry , Amination , Azetidines/chemistry , Bromine Compounds/chemistry , Catalysis , Cyclization , Ether/chemistry , Fluorine Compounds/chemistry , Ketones/chemical synthesis , Models, Chemical , Oxidation-Reduction , Temperature , Time Factors , Tosyl Compounds/chemical synthesisABSTRACT
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.
