33662-26-9Relevant articles and documents
Mild, Rapid, and Chemoselective Procedure for the Introduction of the 9-Phenyl-9-fluorenyl Protecting Group into Amines, Acids, Alcohols, Sulfonamides, Amides, and Thiols
Soley, Jacob,Taylor, Scott D.
, (2020/02/04)
The 9-phenyl-9-fluorenyl (PhF) group has been used as an Nα protecting group of amino acids and their derivatives mainly as a result of its ability to prevent racemization. However, installing this group using the standard protocol, which employs 9-bromo-9-phenylfluorene/K3PO4/Pb(NO3)2, often takes days and yields can be variable. Here, we demonstrate that the PhF group can be introduced into the amino group of Weinreb's amides and methyl esters of amino acids, as well as into alcohols and carboxylic acids, rapidly and in excellent yields, using 9-chloro-9-phenylfluorene (PhFCl)/N-methylmorpholine (NMM)/AgNO3. Nα-PhF-protected amino acids can be prepared from unprotected α-amino acids, rapidly and often in near quantitative yields, by treatment with N,O-bis(trimethylsilyl)acetamide (BSA) and then PhFCl/NMM/AgNO3. Primary alcohols can be protected with the PhF group in the presence of secondary alcohols in moderate yield. Using PhFCl/AgNO3, a primary alcohol can be protected in good yield in the presence of a primary ammonium salt or a carboxylic acid. Primary sulfonamides and amides can be protected in moderate to good yields using phenylfluorenyl alcohol (PhFOH)/BF3·OEt2/K3PO4, while thiols can be protected in good to excellent yield using PhFOH/BF3·OEt2 even in the presence of a carboxylic acid or primary ammonium group.
Toward Orally Absorbed Prodrugs of the Antibiotic Aztreonam. Design of Novel Prodrugs of Sulfate Containing Drugs. Part 2
Ding, Pingyu,Duncton, Matthew A. J.,Fan, Dazhong,Gordon, Eric M.,Grygorash, Ruslan,Li, Xianfeng,Low, Eddy,Ni, Zhi-Jie,Qi, Longwu,Sun, Jiawei,Wang, Brian J.,Yu, Guijun
supporting information, p. 162 - 165 (2020/01/31)
Aztreonam, first discovered in 1980, is an FDA approved, intravenous, monocyclic beta-lactam antibiotic. Aztreonam is active against Gram-negative bacteria and is still used today. The oral bioavailability of aztreonam in humans is less than 1%. Herein we describe the design and synthesis of potential oral prodrugs of aztreonam.
General Fmoc-Based Solid-Phase Synthesis of Complex Depsipeptides Circumventing Problematic Fmoc Removal
Lobo-Ruiz, Ariadna,Tulla-Puche, Judit
supporting information, p. 183 - 192 (2020/01/24)
Development of an Fmoc-based solid-phase depsipeptide methodology has been hampered by base-promoted fragmentation and diketoperazine formation upon Fmoc group elimination. Such a strategy would be a useful tool given the number of commercially available Fmoc-protected residues. Herein we report that the addition of small percentages of organic acids to the Fmoc-removal cocktail proves effective to circumvent these drawbacks and most importantly, allowed the development of an exclusively solid-phase stepwise methodology to prepare a highly complex depsipeptide with multiple and consecutive esters bonds. Alongside, the optimal protecting group scheme for residue incorporation, which is not as straightforward as it is for traditional peptide synthesis, was explored. The developed stepwise strategy proved effective for the synthesis of a highly complex cyclodepsipeptide, being comparable to the yields obtained when using traditional combined chemistry approaches.
