565-70-8Relevant articles and documents
Mechanistic studies of 1-aminocyclopropane-1-carboxylate deaminase: Characterization of an unusual pyridoxal 5′-phosphate-dependent reaction
Thibodeaux, Christopher J.,Liu, Hung-Wen
, p. 1950 - 1962 (2011)
1-Aminocyclopropane-1-carboxylic acid (ACC) deaminase (ACCD) is a pyridoxal 5′-phosphate (PLP)-dependent enzyme that cleaves the cyclopropane ring of ACC, to give α-ketobutyric acid and ammonia as products. The cleavage of the Cα-Cβ bond of an amino acid substrate is a rare event in PLP-dependent enzyme catalysis. Potential chemical mechanisms involving nucleophile- or acid-catalyzed cyclopropane ring opening have been proposed for the unusual transformation catalyzed by ACCD, but the actual mode of cyclopropane ring cleavage remains obscure. In this report, we aim to elucidate the mechanistic features of ACCD catalysis by investigating the kinetic properties of ACCD from Pseudomonas sp. ACP and several of its mutant enzymes. Our studies suggest that the pKa of the conserved active site residue, Tyr294, is lowered by a hydrogen bonding interaction with a second conserved residue, Tyr268. This allows Tyr294 to deprotonate the incoming amino group of ACC to initiate the aldimine exchange reaction between ACC and the PLP coenzyme and also likely helps to activate Tyr294 for a role as a nucleophile to attack and cleave the cyclopropane ring of the substrate. In addition, solvent kinetic isotope effect (KIE), proton inventory, and 13C KIE studies of the wild type enzyme suggest that the Cα-C β bond cleavage step in the chemical mechanism is at least partially rate-limiting under kcat/Km conditions and is likely preceded in the mechanism by a partially rate-limiting step involving the conversion of a stable gem-diamine intermediate into a reactive external aldimine intermediate that is poised for cyclopropane ring cleavage. When viewed within the context of previous mechanistic and structural studies of ACCD enzymes, our studies are most consistent with a mode of cyclopropane ring cleavage involving nucleophilic catalysis by Tyr294.
Structural elucidation of aculeximycin. III. Planar structure of aculeximycin, belonging to a new class of macrolide antibiotics
Murata,Suzuki,Tabayashi,Hattori,Takada,Harada,Suzuki,Ikemoto,Shibuya,Haneishi,Torikata,Itezono,Nakayama
, p. 838 - 849 (1995)
The planar structure of aculeximycin (1) produced by Streptosporangium albidum has been determined by spectral methods and chemical degradations such as 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU)-methanol reaction, ozonolysis, and periodative oxidation. The antibiotic consists of a 30-membered polyhydroxy lactone ring, α or, β-unsaturated ester group, an intramolecular hemiketal, an oligosaccharide (aculexitriose), a neutral sugar and an amino sugar. The structure of aculeximycin is closely related to those of sporaviridins produced by Streptosporangium viridogriseum. We consider that aculeximycin and sporaviridins belong to a new class of macrolide antibiotics, which is different from the polyol macrolides produced by Streptomyces.
PtII-Catalyzed Hydroxylation of Terminal Aliphatic C(sp3)?H Bonds with Molecular Oxygen
Janssen, Michiel,De Vos, Dirk E.
supporting information, p. 10724 - 10734 (2019/07/15)
The practical application of Shilov-type Pt catalysis to the selective hydroxylation of terminal aliphatic C?H bonds remains a formidable challenge, due to difficulties in replacing PtIV with a more economically viable oxidant, particularly O2. We report the potential of employing FeCl2 as a suitable redox mediator to overcome the kinetic hurdles related to the direct use of O2 in the Pt reoxidation. For the selective conversion of butyric acid to γ-hydroxybutyric acid (GHB), a significantly enhanced catalyst activity and stability (turnover numbers (TON)>30) were achieved under 20 bar O2 in comparison to current state-of-the-art systems (TON0 was prevented by the addition of monodentate pyridine derivatives, such as 2-fluoropyridine, but also by introducing varying partial pressures of N2 in the gaseous atmosphere. Finally, stability tests revealed the involvement of PtII and FeCl2 in catalyzing the non-selective overoxidation of GHB. Accordingly, in situ esterification with boric acid proved to be a suitable strategy to maintain enhanced selectivities at much higher conversions (TON>60). Altogether, a useful catalytic system for the selective hydroxylation of primary aliphatic C?H bonds with O2 is presented.
PROCESSES FOR PREPARATION OF IDELALISIB AND INTERMEDIATES THEREOF
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Page/Page column 34; 35, (2016/07/27)
The present application provides processes for preparation of Idelalisib and intermediates thereof. The present application also provides a process for purification of Idelalisib.
