And eight) or N,N-dimethylthiocarbamoyl chloride (Table 1, entries 6 and 9). It really is worth noting that the bulky carbamoyl chlorides (i.e., N,N-diethylcarbamoyl chloride and N,N-dimethylthiocarbamoyl chloride) substantially reduce the conversion rates when compared with N,N-dimethylcarbamoyl chloride beneath the exact same set of carbamoylation PF-06454589 In stock situations (Table 1).Molecules 2021, 26, 6421 PEER Review Molecules 2021, 26, x FOR44of 16 ofScheme two. Carbamoylation of five,7,20-O-trimethylsilybin. Scheme two. Carbamoylation of 5,7,20-O-trimethylsilybin.Table 1. Reaction situations and yields for the carbamoylation of five,7,20-O-trimethylsilybin (three). As well as getting the important 3-O-carbamoyl-5,7,20-O-trimethylsilybin (5) inEntry 1 two 3 4 5 six 7 8Entry 1 2 3 four 5 6 7 879 yield, a small amount of Reaction Situations Dicarbamoyl3-Carbamoyl5,7,20-O-trimethyl-3,23-O-di-(N,N-dimethylcarbamoyl)silybin (four) was also isolated in SM a a a product item Et3 N DMAP DCM Temp. Time 13 yield (Table 1, entry 1). Adding DMPO Chemical additional triethyl amine and DMAP, prolonging reaction Me2 NCOCl (four eq) 4time, or eqincreasing reaction temperature can slightly enhance the (13 ) eq 1 0.1 M r.t. 16 h three (0 ) five (79 ) four yields for Et2 NCOCl (4 eq) 4 eq 1 eq 0.1 M r.t. 16 h three (50 ) six (34 ) 7 (9 ) Me2 NCSCl (4 eq) 43,23-O-dicarbamoylsilbybin (4), but h eq 1 eq 0.1 M r.t. 16 cannot3promote the completion of carbamoylation at (59 ) eight (25 ) 9 (7 ) Me2 NCOCl (4 eq) 4the major alcoholic hydroxyl group at C-23 (Table 1, entries four and 7). This regioseleceq 1 eq 0.1 M 50 C 16 h three (0 ) five (73 ) four (23 ) Et2 NCOCl (4 eq) four eq 1 eq 0.1 M 50 C 16 h three (29 ) six (46 ) 7 (19 ) tive carbamoylation in 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 3 (40 ) 9 C other carbamoyl Mchlorides. A 16 related three (0 ) tendency was observed when reacting Me2 NCOCl (6 eq) 6 eq 3 eq 0.2 50 h 5 (58 ) 4 (38 ) Et2 NCOC (6 eq) 65,7,20-O-trimethylsilybin (three) with16 h eq 3 eq 0.two M 50 C three (0 ) (69 ) (24 ) N,N-diethylcarbamoyl6chloride (Table 1, 7entries five and Me2 NCSCl (6 eq) 6 eq 3 eq 0.2 M 50 C 16 h three (7 ) eight (58 ) 9 (25 ) eight) or N,N-dimethylthiocarbamoyl chloride (Table 1, entries 6 and 9). It is worth noting a Isolated that the bulky carbamoylyields. chlorides (i.e., N,N-diethylcarbamoyl chloride and N,N-dimethylthiocarbamoyl chloride) significantly reduce the conversion rates when 2.2. Structure Determination of 3-O-Carbamoyl-5,7,20-O-trimethylsilybin five compared with N,N-dimethylcarbamoyl chloride under exactly the same set of carbamoylation The structure of conditions (Table 1). five,7,20-O-trimethyl-3-O-(N,N-dimethylcarbamoyl)-silybin (5) was elucidated by interpreting its 1D- and 2D-NMR information (Table two), also as higher resolution MS and IR data. The structure of 5 was characterized by the existence Table 1. Reaction conditions and yields for the carbamoylation of five,7,20-O-trimethylsilybin (3).of 1 signal at 2.85 ppm representing six protons in its 1 H NMR spectrum (Supplementary Supplies) and Reaction Situations Dicarbamoyl3-Carbamoyl13 at (Thio)carbamoyl Chloride 36.75 (36.08) and 155.28 in its C NMR spectrum aan extra dimethylcarbamoyl SM for solution a item a Et3N DMAP DCM Temp. Time group when compared with all the beginning material 5,7,20-O-trimethylsilybin (3), which was three (0 ) five (79 ) four (13 ) Me2NCOCl (4 eq) 4 eq 1 eq 0.1 M r.t. 16 h The three (50 ) six (34 ) 7 to 3-OH Et2NCOCl (4 eq) corroborated by the HRMS information. r.t. dimethylcarbamoyl group in five w.