107289-17-8Relevant articles and documents
Inhibition of invasion and capillary-like tube formation by retrohydroxamate-based MMP inhibitors
Choi, Seung-Su,Ji, Ae-Ri,Yu, Seung-Woo,Cho, Bong-Hwan,Park, Jung Dae,Park, Jun Hyoung,Lee, Hyun Soo,Ryu, Seong Eon,Kim, Dong Han,Kang, Jae-Hoon,Lee, Seung-Taek
scheme or table, p. 2032 - 2038 (2012/01/14)
Matrix metalloproteinases (MMPs), a family of zinc-containing endopeptidases, participate in many normal processes such as embryonic development and wound repair, and in many pathological situations such as cancer, atherosclerosis, and arthritis. Peptidomimetic MMP inhibitors were designed and synthesized with Nformylhydroxylamine (retrohydroxamate) as a zinc-binding group and various side chains on the α, P1′, and P2′ positions. Using in vitro MMP assays with purified MMPs (MMP-1, MMP-2, MMP-3, MMP-9, and MMP-14) and fluorogenic peptide substrates, it was found that compounds 2d and 2g selectively inhibit gelatinases (MMP-2 and MMP-9) and interstitial collagenase (MMP-1). They also inhibited the chemo-invasion of fibrosarcoma HT-1080 cells and tube formation of human umbilical vascular endothelial cells in a dosedependent manner. Our results suggest that retrohydroxamate-based MMP inhibitors, especially compounds 2d and 2g, have the potential to be used as therapeutic drugs for cancer and other MMP-related diseases.
128. α-Alkylierung von β-Hydroxycarbonsaeuren ueber 1,3-Dioxan-4-on-Enolate. Highly Diastereoselective α-Alkylation of β-Hydroxycarboxylic Acids Through Lithium Enolates of 1,3-Dioxan-4-ones
Zimmermann, Juerg,Seebach, Dieter,Ha, Tae-Kyu
, p. 1143 - 1155 (2007/10/02)
From serine, β-hydroxyisobutyric acid ("Roche" acid) and β-hydroxybutyric acid, the dioxanones 1-6 were prepared.The generation of the enolates of type 1 with LDA at -75 deg C and alkylation gave products with trans-configuration whereas protonation of the 5-methyl-substituted enolate allowed access to the cis-configurated β-hydroxybutyric-acid derivative 12.Hydrolysis gave the free β-hydroxy acids of "syn"- and "anti"-configuration.Alkylation of the 6-unsubstituted dioxanones 1 and 3 yielded predominantly products resulting from attack in the cis-position of the t-Bu group.The "reactive" conformation of the enolates involved is tentatively derived from the product configuration.The selectivity of the alkylation is also discussed in terms of the results of an ab-initio calculation on the enolates M-P.
THE STEREOSELECTIVE α-ALKYLATION OF CHIRAL β-HYDROXY ESTERS AND SOME APPLICATIONS THEREOF
Frater, G.,Mueller, U.,Guenther, W.
, p. 1269 - 1278 (2007/10/02)
The stereoselectivity of the α-alkylation of chiral β-hydroxy ester is discussed.The configuration of the alkylated product was proved chemically (Scheme 2) .A one pot aldol-alkylation reaction was developed leading stereoselectively to racemic(S*,S*)-α-alkyl-β-hydroxy ester (Scheme 3,4) .Baker's yeast reduction of 2-alkyl-3-keto ester led to valuable chiral (2RS,3S)-intermediates, which were converted via the corresponding dianion to compounds with a chiral quaternary C atom (Scheme 6) .Synthetic applications of the above findings are shown in the synthesis of various chiral compounds (Scheme 8 and 9) .
