And eight) or N,N-dimethylthiocarbamoyl chloride (Table 1, entries six and 9). It is actually worth

And eight) or N,N-dimethylthiocarbamoyl chloride (Table 1, entries six and 9). It is actually worth noting that the bulky carbamoyl chlorides (i.e., N,N-diethylcarbamoyl chloride and N,N-dimethylthiocarbamoyl chloride) substantially lower the conversion rates when compared with N,N-dimethylcarbamoyl chloride beneath the exact same set of carbamoylation situations (Table 1).Molecules 2021, 26, 6421 PEER Review Molecules 2021, 26, x FOR44of 16 ofScheme 2. Carbamoylation of five,7,20-O-trimethylsilybin. Scheme two. Carbamoylation of 5,7,20-O-trimethylsilybin.Table 1. Reaction conditions and yields for the carbamoylation of 5,7,20-O-trimethylsilybin (3). As well as obtaining the main 3-O-carbamoyl-5,7,20-O-trimethylsilybin (5) inEntry 1 2 three four 5 6 7 8Entry 1 two 3 4 five 6 7 879 yield, a small PX-478 site amount of Reaction Conditions Dicarbamoyl3-Carbamoyl5,7,20-O-trimethyl-3,23-O-di-(N,N-dimethylcarbamoyl)silybin (4) was also isolated in SM a a a product solution Et3 N DMAP DCM Temp. Time 13 yield (Table 1, entry 1). Adding additional triethyl amine and DMAP, prolonging reaction Me2 NCOCl (four eq) 4time, or eqincreasing reaction temperature can slightly boost the (13 ) eq 1 0.1 M r.t. 16 h three (0 ) five (79 ) 4 yields for Et2 NCOCl (4 eq) 4 eq 1 eq 0.1 M r.t. 16 h 3 (50 ) six (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 ) 8 (25 ) 9 (7 ) Me2 NCOCl (4 eq) 4the primary alcoholic hydroxyl group at C-23 (Table 1, entries 4 and 7). This regioseleceq 1 eq 0.1 M 50 C 16 h 3 (0 ) 5 (73 ) 4 (23 ) Et2 NCOCl (4 eq) four eq 1 eq 0.1 M 50 C 16 h 3 (29 ) six (46 ) 7 (19 ) tive carbamoylation in the secondary alcoholic hydroxyl 8 (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) 6 eq three eq 0.2 50 h 5 (58 ) 4 (38 ) Et2 NCOC (6 eq) 65,7,20-O-trimethylsilybin (three) with16 h eq 3 eq 0.2 M 50 C three (0 ) (69 ) (24 ) N,PF-06454589 Protocol N-diethylcarbamoyl6chloride (Table 1, 7entries 5 and Me2 NCSCl (six eq) 6 eq 3 eq 0.2 M 50 C 16 h three (7 ) eight (58 ) 9 (25 ) 8) or N,N-dimethylthiocarbamoyl chloride (Table 1, entries 6 and 9). It truly is worth noting a Isolated that the bulky carbamoylyields. chlorides (i.e., N,N-diethylcarbamoyl chloride and N,N-dimethylthiocarbamoyl chloride) substantially decrease the conversion rates when two.two. 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). 5,7,20-O-trimethyl-3-O-(N,N-dimethylcarbamoyl)-silybin (5) was elucidated by interpreting its 1D- and 2D-NMR data (Table 2), also as higher resolution MS and IR data. The structure of 5 was characterized by the existence Table 1. Reaction circumstances and yields for the carbamoylation of 5,7,20-O-trimethylsilybin (3).of one signal at two.85 ppm representing 6 protons in its 1 H NMR spectrum (Supplementary Components) 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 product a item a Et3N DMAP DCM Temp. Time group when compared using the starting material 5,7,20-O-trimethylsilybin (three), which was 3 (0 ) 5 (79 ) 4 (13 ) Me2NCOCl (4 eq) four eq 1 eq 0.1 M r.t. 16 h The three (50 ) six (34 ) 7 to 3-OH Et2NCOCl (four eq) corroborated by the HRMS information. r.t. dimethylcarbamoyl group in 5 w.