93525-28-1Relevant articles and documents
First total synthesis and phytotoxic activity of Streptomyces sp. metabolites abenquines
Nain-Perez, Amalyn,Barbosa, Luiz C.A.,Maltha, Celia R.A.,Forlani, Giuseppe
, p. 1811 - 1814 (2016/04/05)
The first total synthesis of abenquines A, B2, C and D has been achieved in three steps starting from commercially available 2,5-dimethoxyaniline, with overall yields of 41-61%. Four analogues bearing the amino acids d-valine (17), l-methionine (18), and glycine (19), and benzylamine (20), were also prepared in 45-72% yield. The inhibitory properties of these compounds were evaluated against the photoautotrophic growth of a model Synechococcus sp. strain. Abenquine C and its enantiomer were substantially ineffective, whereas all other abenquines significantly inhibited cell proliferation, with concentrations causing 50%-inhibition of algal growth ranging from 10-5 to 10-6 M.
Design of a hydrogen peroxide-activatable agent that specifically targets cancer cells
Vadukoot, Anish K.,Abdulsalam, Safnas F.,Wunderlich, Mark,Pullen, Eboni D.,Landero-Figueroa, Julio,Mulloy, James C.,Merino, Eddie J.
supporting information, p. 6885 - 6892 (2015/02/02)
Some cancers, like acute myeloid leukemia (AML), use reactive oxygen species to endogenously activate cell proliferation and angiogenic signaling cascades. Thus many cancers display increases in reactive oxygen like hydrogen peroxide concentrations. To translate this finding into a therapeutic strategy we designed new hydrogen peroxide-activated agents with two key molecular pharmacophores. The first pharmacophore is a peroxide-acceptor and the second is a pendant amine. The acceptor is an N-(2,5-dihydroxyphenyl)acetamide susceptible to hydrogen peroxide oxidation. We hypothesized that selectivity between AML and normal cells could be achieved by tuning the pendant amine. Synthesis and testing of fourteen compounds that differed at the pendent amine led to the identification of an agent (14) with 2 μM activity against AML cancer cells and an eleven fold-lower activity in healthy CD34+ blood stem cells. Interestingly, analysis shows that upon oxidation the pendant amine cyclizes, ejecting water, with the acceptor to give a bicyclic compound capable of reacting with nucleophiles. Preliminary mechanistic investigations show that AML cells made from addition of two oncogenes (NrasG12D and MLL-AF9) increase the ROS-status, is initially an anti-oxidant as hydrogen peroxide is consumed to activate the pro-drug, and cells respond by upregulating electrophilic defense as visualized by Western blotting of KEAP1. Thus, using this chemical approach we have obtained a simple, potent, and selective ROS-activated anti-AML agent.
Polymer-supported hypervalent iodine reagents in 'clean' organic synthesis with potential application in combinatorial chemistry
Ley, Steven V.,Thomas, Andrew W.,Finch, Harry
, p. 669 - 671 (2007/10/03)
A clean oxidation reaction of a variety of substrates using polymer-supported (diacetoxyiodo)benzene (PSDIB) which proceeds in high to excellent yield with maximum purity is described including isolation and regeneration of the polymer reagent.
Synthesis of (-)-LL-C10037α and related manumycin-type epoxyquinols
Wipf,Kim,Jahn
, p. 1549 - 1561 (2007/10/02)
Starting with N-allyloxycarbonyl-protected 2,5-dimethoxyaniline, hypervalent iodine oxidation protocols and selective enone epoxidation provides the Streptomyces metabolite LL-C10037α in nine steps and 7-10% overall yield. In an asymmetric variant of this strategy, (R,R)-pentane-2,4-diol is used as a chiral acetalization agent. The resulting semiquinone spiroacetal, due to an ortho-acylamino substituent that restricts the 1,3-dioxane ring conformation, undergoes face-selective epoxidation and is further functionalized to give (-)-LL-C10037α in 94% ee. These pathways represent the first syntheses of the highly functionalized mC7N core of the manumycins and have been further extended toward the preparation of analogs for SAR studies of this class of antitumor antibiotics. Manumycins inhibit the farnesylation of Ras-protein by PFTase (protein farnesyltransferase).
Biosynthesis of Antibiotic LL-C10037α: The Steps beyond 3-Hydroxyanthranilic Acid
Gould, Steven J.,Shen, Ben,Whittle, Yvonne G.
, p. 7932 - 7938 (2007/10/02)
The six steps from 3-hydroxyanthranilic acid to the epoxyquinol LL-C10037α, 1, produced by Streptomyces LL-C10037 have been determined by whole-cell feedings with deuterated substrates and by cell-free studies. 3-Hydroxyanthranilic acid, 2, is decarboxylated to 2-hydroxyaniline, 11, and then oxidized to 2,5-dihydroxyaniline, 8.Acetylation at nitrogen and oxidation afford acetamido-1,4-benzoquinone, 4.A crude cell-free preparation has been found to epoxidize 4 to the epoxyquinone 16 in the presence of O2 and either NaDH or NADPH.Reduction of 16 yields 1.Therelationship of this pathway to that of fungi that produce patulin via analogous intermediates from 6-methylsalicylic acid is discussed.
