93413-06-0Relevant articles and documents
An iterative, bimodular nonribosomal peptide synthetase that converts anthranilate and tryptophan into tetracyclic asperlicins
Gao, Xue,Jiang, Wei,Jimenez-Oses, Gonzalo,Choi, Moon Seok,Houk, Kendall N.,Tang, Yi,Walsh, Christopher T.
, p. 870 - 878 (2013)
The bimodular 276 kDa nonribosomal peptide synthetase AspA from Aspergillus alliaceus, heterologously expressed in Saccharomyces cerevisiae, converts tryptophan and two molecules of the aromatic β-amino acid anthranilate (Ant) into a pair of tetracyclic peptidyl alkaloids asperlicin C and D in a ratio of 10:1. The first module of AspA activates and processes two molecules of Ant iteratively to generate a tethered Ant-Ant-Trp-S-enzyme intermediate on module two. Release is postulated to involve tandem cyclizations, in which the first step is the macrocyclization of the linear tripeptidyl-S-enzyme, by the terminal condensation (CT) domain to generate the regioisomeric tetracyclic asperlicin scaffolds. Computational analysis of the transannular cyclization of the 11-membered macrocyclic intermediate shows that asperlicin C is the kinetically favored product due to the high stability of a conformation resembling the transition state for cyclization, while asperlicin D is thermodynamically more stable.
Procedure - Economical enantioselective total syntheses of asperlicins C and e
Huang, Pei-Qiang,Wang, Yu,Luo, Shi-Peng,Geng, Hui,Ruan, Yuan-Ping,Wang, Ai-E
, p. 1255 - 1258 (2015/03/04)
We report a procedure - economical method for the highly enantioselective and protecting-group free total syntheses of nonpeptidal CCK antagonists asperlicins C and E. Starting from l-tryptophan, the synthesis of asperlicin C has been achieved in three steps, which features the low-valent titanium (LVT: TiCl4-Zn combination)-mediated reductive cyclization of o-nitrobenzamide to construct the (3H)-quinazolin-4-one moiety. This is the first employment of LVT for the synthesis of asperlicin C, which allowed accessing asperlicin C in >99% enantioselectivity. Asperlicin C was converted, in one-pot, into asperlicin E and 2,3-di-epi-asperlicin E by dimethyl dioxirane (DMDO)-mediated tandem reactions. The use of DMDO as a green, cheap, and easily available oxidant to replace the photochemical method renders the synthesis of asperlicin E experimentally convenient.
Assembly of asperlicin peptidyl alkaloids from anthranilate and tryptophan: A two-enzyme pathway generates heptacyclic scaffold complexity in asperlicin E
Haynes, Stuart W.,Gao, Xue,Tang, Yi,Walsh, Christopher T.
supporting information, p. 17444 - 17447 (2013/01/15)
Members of the asperlicin family of fungal metabolites produced by Aspergillus alliaceus are known potent CCKA antagonists. Herein, we report the identification of the gene cluster responsible for directing their biosynthesis. We validate and probe the pathway by genetic manipulation, and provide the first biochemical characterization of the oxidative cyclization en route to the heptacyclic asperlicin E by reconstituting the activity of the FAD depend monooxygenase AspB. This report provides the first genetic characterization of a NRPS assembly line that efficiently activates two anthranilate building blocks and illustrates the remarkably efficient biosynthesis of the complex heptacyclic asperlicin E.
Total synthesis of asperlicin C, circumdatin F, demethylbenzomalvin A, demethoxycircumdatin H, sclerotigenin, and other fused quinazolinones
Tseng, Ming-Chung,Yang, Huei-Yun,Chu, Yen-Ho
experimental part, p. 419 - 427 (2010/02/16)
Using scandium triflate and microwaves, the direct double dehydrocyclization of anthranilate-containing tripeptides was achieved, affording the total syntheses of (i) quinazolino[3,2-a]benzodiazepinediones (1a-f), (ii) diazepino[2,1-b]quinazolinediones (2a-e), and (iii) pyrazino[2,1-b]quinazolinediones (3a-e) with good overall isolated yields (23-43%, 37-47% and 31-56%, respectively). Among the quinazolino[3,2-a] benzodiazepinediones synthesized, 1a (sclerotigenin), 1b (circumdatin F), and 1f (asperlicin C) are natural products.
Microwave-assisted concise total syntheses of quinazolinobenzodiazepine alkaloids
Liu, Ji-Feng,Kaselj, Mira,Isome, Yuko,Chapnick, Jennifer,Zhang, Bailin,Bi, Grace,Yohannes, Daniel,Yu, Libing,Baldino, Carmen M.
, p. 10488 - 10493 (2007/10/03)
One-pot total syntheses of the quinazolinobenzodiazepine alkaloids sclerotigenin (1), (±)-circumdatin F (2), and (±)-asperlicin C (3) via novel microwave-assisted domino reactions were achieved in 55%, 32%, and 20% yields, respectively, from commercially
