26988-87-4Relevant academic research and scientific papers
Inhibition of Escherichia coli tryptophan indole-lyase by tryptophan homologues
Do, Quang T.,Nguyen, Giang T.,Celis, Victor,Phillips, Robert S.
, p. 20 - 26 (2014/11/08)
We have designed, synthesized and evaluated homotryptophan analogues as possible mechanism-based inhibitors for Escherichia coli tryptophan indole-lyase (tryptophanase, TIL, E.C. 4.1.99.1). As a quinonoid structure is an intermediate in the reaction mechanism of TIL, we anticipated that homologation of the physiological substrate, l-Trp would provide analogues resembling the transition state for β-elimination, and potentially inhibit TIL. Our results demonstrate that l-homotryptophan (1a) is a moderate competitive inhibitor of TIL, with Ki = 67 μM, whereas l-bishomotryptophan (1b) displays more potent inhibition, with Ki = 4.7 μM. Pre-steady-state kinetics indicated the formation of an external aldimine and quinonoid with 1a, but only the formation of an external aldimine for 1b, suggesting differences in the inhibition mechanism. These results demonstrate that formation of a quinonoid complex is not required for strong inhibition. In addition, the Trp analogues were evaluated as inhibitors of Salmonella typhimurium Trp synthase. Our results indicate that compound 1b is at least 25-fold more selective toward TIL than Trp synthase. We report that compound 1b is comparable to the most potent inhibitor previously reported, while displaying high selectivity for TIL. Thus, 1b is a potential lead for the development of novel antibacterials.
Efficient asymmetric synthesis of biologically important tryptophan analogues via a palladium-mediated heteroannulation reaction
Ma,Liu,Li,Flippen-Anderson,Yu,Cook
, p. 4525 - 4542 (2007/10/03)
A novel and concise synthesis of optically active tryptophan derivatives was developed via a palladium-catalyzed heteroannulation reaction of substituted o-iodoanilines with an internal alkyne. The required internal alkyne 14a or 25 was prepared in greater than 96% de via alkylation of the Schoellkopf chiral auxiliary 19 employing diphenyl phosphate as the leaving group. The Schoellkopf chiral auxiliary was chosen here for the preparation of L-tryptophans would be available from D-valine while the D-isomers required for natural product total synthesis would originate from the inexpensive L-valine (300-g scale). Applications of the palladium-catalyzed heteroannulation reaction were extended to the first asymmetric synthesis of L-isotryptophan 38 and L-benz[f]tryptophan 39. More importantly, the optically pure 6-methoxy-D-tryptophan 62 was prepared by this protocol on a large scale (>300 g). This should permit entry into many ring-A oxygenated indole alkaloids when coupled with the asymmetric Pictet-Spengler reaction. In addition, an improved total synthesis of tryprostatin A (9a) was accomplished in 43% overall yield employing this palladium-mediated process.
Efficient asymmetric synthesis of important tryptophan analogs for biological research via the Schollkopf chiral auxiliary
Ma, Chunrong,Yu, Shu,He, Xiaohui,Liu, Xiaoxiang,Cook, James M.
, p. 2781 - 2785 (2007/10/03)
An efficient method has been developed via the Schollkopf chiral auxiliary for the asymmetric synthesis of the important tryptophan analogs: L-isotryptophan, L-benzo[f]tryptophan and L-homotryptophan. (C) 2000 Elsevier Science Ltd.
