And 8) or N,N-dimethylthiocarbamoyl Inositol nicotinate supplier chloride (Table 1, entries 6 and 9). It is actually worth noting that the bulky carbamoyl chlorides (i.e., N,N-diethylcarbamoyl chloride and N,N-dimethylthiocarbamoyl chloride) considerably lower the conversion prices when compared with N,N-dimethylcarbamoyl chloride beneath the identical set of carbamoylation conditions (Table 1).Molecules 2021, 26, 6421 PEER Overview Molecules 2021, 26, x FOR44of 16 ofScheme two. Carbamoylation of 5,7,20-O-trimethylsilybin. Scheme two. Carbamoylation of 5,7,20-O-trimethylsilybin.Table 1. Reaction circumstances and yields for the carbamoylation of five,7,20-O-trimethylsilybin (three). As well as obtaining the key 3-O-carbamoyl-5,7,20-O-trimethylsilybin (five) inEntry 1 2 3 four five 6 7 8Entry 1 2 3 four five six 7 879 yield, a smaller Polmacoxib Immunology/Inflammation volume of Reaction Circumstances Dicarbamoyl3-Carbamoyl5,7,20-O-trimethyl-3,23-O-di-(N,N-dimethylcarbamoyl)silybin (four) was also isolated in SM a a a solution product Et3 N DMAP DCM Temp. Time 13 yield (Table 1, entry 1). Adding far more triethyl amine and DMAP, prolonging reaction Me2 NCOCl (four eq) 4time, or eqincreasing reaction temperature can slightly raise the (13 ) eq 1 0.1 M r.t. 16 h three (0 ) five (79 ) four yields for Et2 NCOCl (4 eq) four eq 1 eq 0.1 M r.t. 16 h 3 (50 ) 6 (34 ) 7 (9 ) Me2 NCSCl (four eq) 43,23-O-dicarbamoylsilbybin (four), but h eq 1 eq 0.1 M r.t. 16 cannot3promote the completion of carbamoylation at (59 ) eight (25 ) 9 (7 ) Me2 NCOCl (four eq) 4the principal alcoholic hydroxyl group at C-23 (Table 1, entries four and 7). This regioseleceq 1 eq 0.1 M 50 C 16 h 3 (0 ) five (73 ) four (23 ) Et2 NCOCl (four eq) four eq 1 eq 0.1 M 50 C 16 h 3 (29 ) 6 (46 ) 7 (19 ) tive carbamoylation at the secondary alcoholic hydroxyl eight (42 ) at C-3 could be(14 ) group extended to Me2 NCSCl (four eq) 4 eq 1 eq 0.1 M 50 C 16 h three (40 ) 9 C other carbamoyl Mchlorides. A 16 similar three (0 ) tendency was observed when reacting Me2 NCOCl (six eq) six eq three eq 0.two 50 h 5 (58 ) 4 (38 ) Et2 NCOC (6 eq) 65,7,20-O-trimethylsilybin (3) with16 h eq 3 eq 0.2 M 50 C three (0 ) (69 ) (24 ) N,N-diethylcarbamoyl6chloride (Table 1, 7entries five and Me2 NCSCl (6 eq) 6 eq 3 eq 0.two M 50 C 16 h three (7 ) 8 (58 ) 9 (25 ) 8) or N,N-dimethylthiocarbamoyl chloride (Table 1, entries 6 and 9). It’s worth noting a Isolated that the bulky carbamoylyields. chlorides (i.e., N,N-diethylcarbamoyl chloride and N,N-dimethylthiocarbamoyl chloride) substantially lower the conversion rates when 2.2. Structure Determination of 3-O-Carbamoyl-5,7,20-O-trimethylsilybin 5 compared with N,N-dimethylcarbamoyl chloride beneath the same set of carbamoylation The structure of situations (Table 1). five,7,20-O-trimethyl-3-O-(N,N-dimethylcarbamoyl)-silybin (five) was elucidated by interpreting its 1D- and 2D-NMR data (Table two), too as higher resolution MS and IR information. The structure of 5 was characterized by the existence Table 1. Reaction situations and yields for the carbamoylation of 5,7,20-O-trimethylsilybin (three).of a single signal at 2.85 ppm representing 6 protons in its 1 H NMR spectrum (Supplementary Components) and Reaction Conditions Dicarbamoyl3-Carbamoyl13 at (Thio)carbamoyl Chloride 36.75 (36.08) and 155.28 in its C NMR spectrum aan additional dimethylcarbamoyl SM for solution a product a Et3N DMAP DCM Temp. Time group when compared using the starting material 5,7,20-O-trimethylsilybin (three), which was three (0 ) 5 (79 ) four (13 ) Me2NCOCl (four eq) 4 eq 1 eq 0.1 M r.t. 16 h The three (50 ) 6 (34 ) 7 to 3-OH Et2NCOCl (four eq) corroborated by the HRMS information. r.t. dimethylcarbamoyl group in 5 w.
