1145-80-8Relevant articles and documents
An alkylidene carbene C-H insertion strategy for the enantioselective synthesis of α,α-dialkyl-α-amino acids
Gabaitsekgosi, Renameditswe,Hayes, Christopher J.
, p. 7713 - 7716 (1999)
A synthesis of the α,α-dialkyl-α-amino acid (1S,3R)-2,5-methano-leucine has been achieved using an alkylidene carbene 1,5-C-H insertion reaction as a key step. Treatment of the ketone 11 with 1.2 equivalents of lithio(trimethylsilyl)diazomethane in THF resulted in the formation of the cyclopentene 13 in 62% yield. The enantiomeric excess of the product 18 was determined to be >95% by chiral HPLC (Chiracel OD column).
A Convenient Synthesis of Methyl 2-thazoline-4-carboxylate, an Important Skeleton of Cyclothiazomycin
Shin, Chung-gi,Ito, Akio,Okumura, Kazuo,Nakamura, Yutaka
, p. 45 - 46 (1995)
The convenient syntheses of a few methyl 2-(1-amino)alkenyl thiazoline-4-carboxylates and methyl 2-thiazoline-4-carboxylate have been accomplished.The latter is an important portial skeleton of macrobicyclic peptide antibiotic cyclothiazomycin.
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.
Design, Synthesis, and Conformation-Activity Study of Unnatural Bridged Bicyclic Depsipeptides as Highly Potent Hypoxia Inducible Factor-1 Inhibitors and Antitumor Agents
Koike, Kota,Nagano, Masanobu,Ebihara, Masahiro,Hirayama, Tasuku,Tsuji, Mieko,Suga, Hiroaki,Nagasawa, Hideko
, p. 4022 - 4046 (2020/06/08)
By carrying out structural modifications based on the bicyclic peptide structure of echinomycin, we successfully synthesized various powerful antitumor derivatives. The ring conformation in the obtained compounds was restricted by cross-linking with an unnatural bond. The prepared derivatives were demonstrated to strongly suppress the hypoxia inducible factor (HIF)-1 transcriptional activation and hypoxia induction of HIF-1 protein expression. Particularly, alkene-bridged derivative 12 exhibited remarkably potent cytotoxicity (IC50 = 0.22 nM on the MCF-7 cell line) and HIF-1 inhibition (IC50 = 0.09 nM), which considerably exceeded those of echinomycin. Conformational analyses and molecular modeling studies revealed that the biological activities were enhanced following restriction of the conformation by cross-linking through a metabolically stable and rigid bridge bond. In addition, we proposed a new globular conformation stabilized by intramolecular πstacking that can contribute to the biological effects of bicyclic depsipeptides. The developments presented in the current study serve as a useful guide to expand the chemical space of peptides in drug discovery.
