6404-28-0Relevant articles and documents
General Access to Modified α-Amino Acids by Bioinspired Stereoselective γ-C?H Bond Lactonization
Vicens, Laia,Bietti, Massimo,Costas, Miquel
supporting information, p. 4740 - 4746 (2020/12/25)
α-Amino acids represent a valuable class of natural products employed as building blocks in biological and chemical synthesis. Because of the limited number of natural amino acids available, and of their widespread application in proteomics, diagnosis, drug delivery and catalysis, there is an increasing demand for the development of procedures for the preparation of modified analogues. Herein, we show that the use of bioinspired manganese catalysts and H2O2 under mild conditions, provides access to modified α-amino acids via γ-C?H bond lactonization. The system can efficiently target 1°, 2° and 3° γ-C?H bonds of α-substituted and achiral α,α-disubstituted α-amino acids with outstanding site-selectivity, good to excellent diastereoselectivity and (where applicable) enantioselectivity. This methodology may be considered alternative to well-established organometallic procedures.
Antitumour benzothiazoles. Part 32: DNA adducts and double strand breaks correlate with activity; Synthesis of 5F203 hydrogels for local delivery
Stone, Erica L.,Citossi, Francesca,Singh, Rajinder,Kaur, Balvinder,Gaskell, Margaret,Farmer, Peter B.,Monks, Anne,Hose, Curtis,Stevens, Malcolm F.G.,Leong, Chee-Onn,Stocks, Michael,Kellam, Barrie,Marlow, Maria,Bradshaw, Tracey D.
supporting information, p. 6891 - 6899 (2015/11/11)
Potent, selective antitumour AhR ligands 5F 203 and GW 610 are bioactivated by CYPs 1A1 and 2W1. Herein we reason that DNA adducts' generation resulting in lethal DNA double strand breaks (DSBs) underlies benzothiazoles' activity. Treatment of sensitive carcinoma cell lines with GW 610 generated co-eluting DNA adducts (R2 > 0.7). Time-dependent appearance of γ-H2AX foci revealed subsequent DNA double strand breaks. Propensity for systemic toxicity of benzothiazoles steered development of prodrugs' hydrogels for localised delivery. Clinical applications of targeted therapies include prevention or treatment of recurrent disease after surgical resection of solid tumours. In vitro evaluation of 5F 203 prodrugs' activity demonstrated nanomolar potency against MCF-7 breast and IGROV-1 ovarian carcinoma cell lines.
AMINO ACID ANALOGUES AND METHODS FOR THEIR SYNTHESIS
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Page/Page column 48; 50, (2014/01/18)
A method for the synthesis of an amino acid analogue or a salt, solvate, derivative, isomer or tautomer thereof comprising the steps of: (i) subjecting an amino acid containing a metathesisable group to metathesis with a compound containing a complementary metathesisable group of formula (I) or (II): (Formulae (I), (II)) wherein R1 and R2 are independently selected from H and substituted or unsubstituted C1 to C4 alkyl; each R3 is either absent or independently selected from a heteroatom, a substituted or unsubstituted C1 to C20 alkyl, and a substituted or unsubstituted C1 to C20 alkyl group interrupted by one or more heteroatoms; and each X is independently selected from H and an effector molecule; in the presence of a reagent to catalyse the metathesis to form a dicarba bridge between the amino acid containing a metathesisable group and the compound containing a complementary metathesisable group; and (ii) reducing the dicarba bridge to form a saturated dicarba bridge, wherein the reagent used to catalyse step (i) also catalyses step (ii).
Tandem Ru-alkylidene-catalysed cross metathesis/hydrogenation: Synthesis of lipophilic amino acids
Wang, Zhen J.,Spiccia, Nicolas D.,Jackson, W. Roy,Robinson, Andrea J.
, p. 470 - 476 (2013/08/23)
Highly efficient synthesis of lipidic amino acids can be achieved via Ru-alkylidene-catalysed cross metathesis of long chain alkenes with commercially available allylglycine. The resultant unsaturated analogues can be then optionally hydrogenated under mi
Enzymatic approach to both enantiomers of N-Boc hydrophobic amino acids
Agosta, Eleonora,Caligiuri, Antonio,D'Arrigo, Paola,Servi, Stefano,Tessaro, Davide,Canevotti, Renato
, p. 1995 - 1999 (2007/10/03)
Protease catalysed hydrolysis of N-Boc-amino acid esters allows us to obtain N-Boc l-acids and d-esters of amino butanoic acid, nor-leucine, nor-valine, leucine and t-leucine in excellent ee. The reaction occurs in short reaction times and high concentrations. When a biphasic system (buffer-MTBE) is employed, a strong solvent effect is observed. This method could be of significance for the preparation of d-t-leucine, for which a practical method is currently unavailable.
Ketoheterocycle-based inhibitors of cathepsin K: A novel entry into the synthesis of peptidic ketoheterocycles
Tavares, Francis X.,Deaton, David N.,Miller, Aaron B.,Miller, Larry R.,Wright, Lois L.
, p. 3891 - 3895 (2007/10/03)
Ketoheterocyclic inhibitors of cathepsin K have been disclosed. SAR of potency enhancing P2-P3 groups coupled with ketoheterocyclic warheads to provide cathepsin K inhibitors have been described. In addition, a novel route to access
Design of small molecule ketoamide-based inhibitors of cathepsin K
Catalano, John G.,Deaton, David N.,Long, Stacey T.,McFadyen, Robert B.,Miller, Larry R.,Payne, J. Alan,Wells-Knecht, Kevin J.,Wright, Lois L.
, p. 719 - 722 (2007/10/03)
A novel series of ketoamide-based inhibitors of cathepsin K has been identified. Modifications to P2 and P3 elements were crucial to enhancing inhibitory activity. Although not optimized, a selected inhibitor was effective in attenua
Exploration of the P1 SAR of aldehyde cathepsin K inhibitors.
Catalano, John G,Deaton, David N,Furfine, Eric S,Hassell, Annie M,McFadyen, Robert B,Miller, Aaron B,Miller, Larry R,Shewchuk, Lisa M,Willard Jr., Derril H,Wright, Lois L
, p. 275 - 278 (2007/10/03)
The synthesis and biological activity of a series of aldehyde inhibitors of cathepsin K are reported. Exploration of the properties of the S(1) subsite with a series of alpha-amino aldehyde derivatives substituted at the P(1) position afforded compounds with cathepsin K IC(50)s between 52 microM and 15 nM.
A plant growth retardant related to chlamydocin and its proposed mechanism of action
Tani, Hiroko,Honma, Tamaki,Fujii, Yuzo,Yoneyama, Koichi,Nakajima, Hiromitsu
, p. 1133 - 1140 (2007/10/03)
A comparison of the plant growth retardant activity of the chlamydocin analogues, compound 1, six derivatives from 1 and 2, and two synthetic analogues revealed that there are two types of retardant in chlamydocin analogues. One, for example in compound 1, requires an oxygen atom at C-8 of the 2-aminodecanoic acid moiety to show retardant activity. The other, for example in compound 8, requires no oxygen atom at C-8 but requires a specific alkyl group chain length for activity. To determine the differences in mode of action of both types of retardant, rice seedlings were separately treated with compounds 1 and 8, and after appearance of dwarfism, their endogenous ABA and GA1 levels were determined and compared to those of the control. Treatment with 1 (10 nmol/plant) increased ABA levels 4 times higher than that of the control and decreased GA1 levels to 20% of that of the control. Treatment with 8 (30 nmol/plant) did not affect the ABA level but decreased GA1 content to 5% of that of the control.
Versatile synthons for optically pure alpha-amino aldehydes and alpha-amino acids: (+)- and (-)-4,5-dialkoxy-2-oxazolidinones.
Morita,Nagasawa,Yahiro,Matsunaga,Kunieda
, p. 897 - 899 (2007/10/03)
Both enantiomers of trans-5-benzyloxy-4-methoxy- (BMOx) and trans-4,5-dimethoxy-2-oxazolidinones (DMOx), which are readily accessible from simple 2-oxazolone heterocycles, represent good candidates for a new class of chiral synthons for use in the preparation of optically pure alpha-amino aldehydes and alpha-amino acids, respectively.
