133066-59-8Relevant articles and documents
N-Thiolated β-lactam antibacterials: Effects of the N-organothio substituent on anti-MRSA activity
Heldreth, Bart,Long, Timothy E.,Jang, Seyoung,Reddy, G. Suresh Kumar,Turos, Edward,Dickey, Sonja,Lim, Daniel V.
, p. 3775 - 3784 (2006)
A study on the structure-activity profiles of N-thiolated β-lactams 1 is reported which demonstrates the importance of the N-organothio moiety on antibacterial activity. Our results indicate that elongation of the N-alkylthio residue beyond two carbons, or extensive branching within the organothio substituent, diminishes antibacterial effects. Of the derivatives we examined, the N-sec-butylthio β-lactam derivative 5g possesses the strongest growth inhibitory activity against methicillin-resistant Staphylococcus aureus strains. Sulfur oxidation state is important, as the N-sulfenyl and N-sulfinyl groups provide for the best antibacterial activity, while lactams bearing the N-sulfonyl or N-sulfonic acid functionalities have much weaker or no anti-MRSA properties. Stereochemistry within the organothio chain does not seem to be a significant factor, although for N-sec-butylthio β-lactams 15a-d, the 3R,4S-lactams 15c, d are more active than the 3S,4R-stereoisomers 15a, b in agar diffusion experiments. The N-methylthio lactams are the most sensitive to the presence of glutathione, followed by N-ethylthio and N-sec-butylthio lactams, which indicates that bioactivity and perhaps bacterial selectivity of the lactams may be related to the amount of organothiols in the bacterial cell. These results support the empirical model for the mechanism of action of the compounds in which the lactam transverses the bacterial membrane to deliver the organothio moiety to its cellular target.
Practical synthesis of 4-aryl- and 4-heteroarylazetidin-2-ones: Applications in the synthesis of the Taxol side chain
Rey,Droghini,Douglas,Vemishetti,Boettger,Racha,Dillon
, p. 2131 - 2136 (1994)
A convenient, high-yielding procedure has been developed for the kilogram-scale synthesis of (±)-cis-3-acetoxy-4-phenylazetidin-2-one (3), a β-lactam that has been used in the semi-synthesis of Taxol. The Staudinger reaction between hydrobenzamide (5) and
ECD spectrometric methods for detecting the enantioselective enzymatic hydrolysis of racemic 3-acetoxy-4-phenyl-β-lactam
Zhang, Xiang,Li, Li,Si, Yi Kang,Yin, Da Li
, p. 1197 - 1200,4 (2012)
(-)-(3R, 4S)-3-Acetoxy-4-phenylazetidin-2-one ((-)-1) was the key intermediate for preparing optical C-13 side-chain moiety in partial synthesis of docetaxel and paclitaxel. It can be successfully prepared via enantioselective hydrolysis of racemic esters
New enzymatic two-step cascade reaction for the preparation of a key intermediate for the taxol side-chain
Forro, Enikoe,Fueloep, Ferenc
, p. 3074 - 3079 (2010)
Enzymatic strategies are reported for the synthesis of (2R, 3S)-3-amino-2-hydroxy-3-phenylpropionic acid (ee > 98%), a key intermediate of the side-chain of Taxolby enzymatic hydrolysis in organic media. The new enzymatic cascade reaction, which took place through Candida antarctica lipase B-catalysed deacylation followed by lactam ring-opening of racemic cis-3-acetoxy-4-phenylazetidin-2-one with H2O in iPr2O at: 60 °C, resulted in two different enantiopure products (ee ≥ 98%), one of them being the desired key intermediate for the side-chain of Taxol.
Biocatalytic synthesis of some chiral pharmaceutical intermediates by lipases
Patel, Ramesh N.,Banerjee, Amit,Szarka, Laszlo J.
, p. 1363 - 1375 (1996)
Chiral intermediates were prepared by biocatalytic processes for the chemical synthesis of three pharmaceutical drug candidates. These include (i) the synthesis of [(3R-cis)-3-(acetyloxy)-4-phenyl-2-azetidinone 2 for the semi-synthesis of paclitaxel (taxol) 5, an anticancer compound; (ii) synthesis of chiral (exo,exo)-7-oxabicyclo [2.2.1] heptane-2,3-dimenthanol monoacetate ester 9 for the chemoenzymatic preparation of a thromboxane A2 antagonist; (iii) the enzymatic synthesis of S-(-) 3-benzylthio-2-methylpropanoic acid, a key chiral intermediate for the synthesis of antihypertensive drugs captopril 10 or zofenopril 13.
Paclitaxel Biosynthesis: Adenylation and Thiolation Domains of an NRPS TycA PheAT Module Produce Various Arylisoserine CoA Thioesters
Muchiri, Ruth,Walker, Kevin D.
, p. 1415 - 1425 (2017/03/23)
Structure-activity relationship studies show that the phenylisoserinyl moiety of paclitaxel (Taxol) is largely necessary for the effective anticancer activity. Several paclitaxel analogues with a variant isoserinyl side chain have improved pharmaceutical
Asymmetric biocatalysis of S-3-amino-3-phenylpropionic acid with new isolated Methylobacterium Y1-6
Li, Yi,Wang, Wenfu,Huang, Yumian,Zou, Qianwen,Zheng, Guojun
, p. 1674 - 1678 (2013/11/19)
β-amino acids are widely used in drug research, and S-3-amino-3-phenylpropionic acid (S-APA) is an important pharmaceutical intermediate of S-dapoxetine, which has been approved for the treatment of premature ejaculation. Chiral catalysis is an excellent method for the preparation of enantiopure compounds. In this study, we used (±)-ethyl-3-amino-3-phenylpropanoate (EAP) as the sole carbon source. Three hundred thirty one microorganisms were isolated from 30 soil samples, and 17 strains could produce S-APA. After three rounds of cultivation and identification, the strain Y1-6 exhibiting the highest enantioselective activity of S-APA was identified as Methylobacterium oryzae. The optimal medium composition contained methanol (2.5 g/L), 1,2-propanediol (7.5 g/L), soluble starch (2.5 g/L), and peptone (10 g/L); it was shaken at 220 rpm for 4-5 days at 30 C. The optimum condition for biotransformation of EAP involved cultivation at 37 C for 48 h with 120 mg of wet cells and 0.64 mg of EAP in 1 ml of transfer solution. Under this condition, substrate ee was 92.1% and yield was 48.6%. We then attempted to use Methylobacterium Y1-6 to catalyze the hydrolytic reaction with substrates containing 3-amino-3-phenyl-propanoate ester, N-substituted-β-ethyl-3-amino-3-phenyl-propanoate, and γ-lactam. It was found that 5 compounds with ester bonds could be stereoselectively hydrolyzed to S-acid, and 2 compounds with γ-lactam bonds could be stereoselectively hydrolyzed to (-)-γ-lactam.
A new enzymatic strategy for the preparation of (2R,3S)-3-phenylisoserine: a key intermediate for the Taxol side chain
Forro, Eniko,Fueloep, Ferenc
scheme or table, p. 637 - 639 (2010/08/03)
Burkholderia cepacia lipase PS-IM catalysed the hydrolysis of racemic ethyl 3-amino-3-phenyl-2-hydroxypropionate with excellent enantioselectivity (E >200), when the reaction was performed with added H2O as a nucleophile, in iPr2O, at 50 °C. The hydrolysis of the less reactive enantiomeric ethyl 3-amino-3-phenyl-2-hydroxypropionate with 18% HCl afforded the corresponding enantiomerically pure (2R,3S)-3-amino-3-phenyl-2-hydroxypropionic acid hydrochloride, a key intermediate for the Taxol side chain.
A new entry to N-unsubstituted β-lactams through a solid-phase approach
Dasgupta, Swapan K.,Banik, Bimal K.
, p. 9445 - 9447 (2007/10/03)
A remarkable new entry to N-unsubstituted β-lactams using rink resin as the solid-support has been developed.
β-lactams, methods for the preparation of taxanes, and sidechain-bearing taxanes
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Page column 11, (2010/01/30)
Novel β-lactams finding utility as intermediates in the preparation of sidechain-bearing taxanes such as taxol and taxol derivatives. The present invention also relates to novel methods of coupling β-lactams to form such sidechain-bearing taxanes, and to novel sidechain-bearing taxanes.
