And 8) or N,N-dimethylthiocarbamoyl chloride (Table 1, entries six and 9). It truly is worth FAUC 365 GPCR/G Protein noting that the bulky carbamoyl chlorides (i.e., N,MNITMT Purity N-diethylcarbamoyl chloride and N,N-dimethylthiocarbamoyl chloride) significantly reduce the conversion rates when compared with N,N-dimethylcarbamoyl chloride under the identical set of carbamoylation situations (Table 1).Molecules 2021, 26, 6421 PEER Assessment Molecules 2021, 26, x FOR44of 16 ofScheme 2. Carbamoylation of 5,7,20-O-trimethylsilybin. Scheme 2. Carbamoylation of five,7,20-O-trimethylsilybin.Table 1. Reaction conditions and yields for the carbamoylation of five,7,20-O-trimethylsilybin (three). As well as acquiring the important 3-O-carbamoyl-5,7,20-O-trimethylsilybin (five) inEntry 1 two 3 4 five 6 7 8Entry 1 two three 4 5 six 7 879 yield, a little amount of Reaction Situations Dicarbamoyl3-Carbamoyl5,7,20-O-trimethyl-3,23-O-di-(N,N-dimethylcarbamoyl)silybin (4) was also isolated in SM a a a item product Et3 N DMAP DCM Temp. Time 13 yield (Table 1, entry 1). Adding more 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 3 (0 ) five (79 ) four yields for Et2 NCOCl (4 eq) four eq 1 eq 0.1 M r.t. 16 h 3 (50 ) six (34 ) 7 (9 ) Me2 NCSCl (four eq) 43,23-O-dicarbamoylsilbybin (4), 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 key 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 ) five (73 ) 4 (23 ) Et2 NCOCl (four 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 8 (42 ) at C-3 might be(14 ) group extended to Me2 NCSCl (four eq) four eq 1 eq 0.1 M 50 C 16 h three (40 ) 9 C other carbamoyl Mchlorides. A 16 related 3 (0 ) tendency was observed when reacting Me2 NCOCl (six eq) 6 eq 3 eq 0.two 50 h five (58 ) four (38 ) Et2 NCOC (6 eq) 65,7,20-O-trimethylsilybin (3) with16 h eq 3 eq 0.2 M 50 C 3 (0 ) (69 ) (24 ) N,N-diethylcarbamoyl6chloride (Table 1, 7entries 5 and Me2 NCSCl (six eq) 6 eq three 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 prices when two.2. Structure Determination of 3-O-Carbamoyl-5,7,20-O-trimethylsilybin 5 compared with N,N-dimethylcarbamoyl chloride below the same set of carbamoylation The structure of conditions (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 2), as well as higher resolution MS and IR data. The structure of five was characterized by the existence Table 1. Reaction situations and yields for the carbamoylation of 5,7,20-O-trimethylsilybin (three).of 1 signal at 2.85 ppm representing 6 protons in its 1 H NMR spectrum (Supplementary Supplies) and Reaction Conditions 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 with all the beginning material 5,7,20-O-trimethylsilybin (three), 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 (four eq) corroborated by the HRMS data. r.t. dimethylcarbamoyl group in 5 w.
