Peptide Synthesis in Aqueous Solution. IV. Preparation and Properties of [p-(Benzyloxycarbonyloxy)phenyl]dimethylsulfonium Methyl Sulfate (Z-ODSP), [p-(t-Butoxycarbonyloxy)phenyl]dimethylsulfonium Methyl Sulfate (Boc-ODSP) and [p-(9-Fluorenylmethyloxycarbonyloxy)phenyl]dimethylsulfonium Methyl Sulfate (Fmoc-ODSP) as Water-Soluble N-Acylating Reagents

Abstract

In order to increase the applications of the water-soluble active ester method, water-soluble acylating reagents, [p-(benzyloxycarbonyloxy)phenyl]dimethylsulfonium methyl sulfate, [p-(t-butoxycarbonyloxy)phenyl]dimethylsulfonium methyl sulfate and [p-(9-fluorenylmethyloxycarbonyloxy)phenyl]dimethylsulfonium methyl sulfate, were synthesized from of p-hydroxyphenyldimethylsulfonium methyl sulfate. These compounds had high solubility (more than 30%) in water and were found to act as excellent water-soluble acylating reagents for the synthesis of N-benzyloxycarbonyl, N-t-butoxycarbonyl, N-9-fluorenylmethyloxycarbonyl amino acid derivatives in aqueous solution. They converted dipeptides to N-acyl-dipeptides in aqueous media as well as amino acids. In addition, they were found to be efficient reagents for protecting the side chains of lysine, ornithine, and cysteine.

Asymmetric Syntheses of N-Boc 2-Substituted Pyrrolidines and Piperidines by Intramolecular Cyclization

“…The combined organic extracts were dried (MgSO 4 ) and concentrated. The crude product was purified by column chromatography (EtOAc) to give N -( tert -butoxycarbonyl)proline as a white solid (23 mg, 10%, mp 130−132 °C [lit . 134−136 °C]): 1 H NMR (CDCl 3 , 400 MHz) δ 1.47 (s, 6H), 1.51 (s, 3H), 1.87−1.95 (br, 2H), 2.04−2.09 (br, 1H), 2.26−2.29 (br, 1H), 3.34−3.46 (br, 2H), 4.10−4.36 (br, 1H); 13 C NMR (CDCl 3 , 100 MHz) mixture of rotamers δ (23.52−24.14), (28.1−28.3), (29.2−30.7), (46.2−46.7), (58.7−58.8), (80.3−80.6), (153.9−155.4), (176.6−178.4); [α] 24 D = −52 ( c = 1, CHCl 3 ), lit .…”

Simultaneous Amino and Carboxyl Group Protection for .alpha.-Branched Amino Acids

“…After drying (MgS04), the volatiles were evaporated in vacuo and the residue purified by flash Si02 chromatography (10% Et20-hexane) to give 3b (1.0 g, 82%) as a white solid: mp 68-70 °C; NMR (500 MHz, CDC13) <5 3.33 (d, J = 13 Hz, 1 H), 3.62 (d, J = 13 Hz, 1 ), 5. 10-5.25 (m, 4 H), 5.27 (d, J= 10 Hz, 1 H), 5.28 (d, J = 17 Hz, 1 H), 5.68 (s, 1), 6.08 (dd, J = 10,17 Hz, 1 ), 6.90-6.91 (m, 2 ), 7. 10-7.20 (m, 3 H), 7.26-7.43 (m, 10 H); 13C NMR (125 MHz, CDC13) <5 40.4, 65.1, 66.5, 67.8,116.2, 126.9,128.1,128.20, 128.23, 128.4, 128.5.128.6.130.0.…”

Fmoc-Amox, A Suitable Reagent for the Introduction of Fmoc

“…For Fmoc introduction using neat aqueous solution, Fmoc-phenyl­dimethyl­sulfonium methyl sulfate (Fmoc-ODsp) has been used, but no formation of dipeptides was studied (Table , #11).…”