57105-58-5

Usage

InChI:InChI=1/C9H12O5/c1-13-9(12)7-5-3-2-4(14-5)6(7)8(10)11/h4-7H,2-3H2,1H3,(H,10,11)

Upstream product

• 6118-51-0 exo-3,6-epoxy-1,2,3,6-tetrahydrophthalic anhydride 
• 67-56-1 methanol 

Downstream Products

• 6253-21-0 3α-hydroxymethyl-7α-oxabicyclo[2.2.1]heptane-2α-carboxylic acid lactone 
• 112918-11-3 ((1R,2S,3S,4S)-3-Hydroxymethyl-7-oxa-bicyclo[2.2.1]hept-2-yl)-carbamic acid benzyl ester 
• 112918-10-2 2-exo-(benzyloxycarbonylamino)-3-exo-formyl-7-oxabicyclo<2.2.1>heptane 
• 112918-10-2 2-exo-(benzyloxycarbonylamino)-3-endo-formyl-7-oxabicyclo<2.2.1>heptane 
• 112918-09-9 methyl 3-exo-(benzyloxycarbonylamino)-7-oxabicyclo<2.2.1>heptane-2-exo-carboxylate 
• 1047659-39-1 3-(4-Benzyl-piperazine-1-carbonyl)-7-oxa-bicyclo[2.2.1]heptane-2-carboxylic acid methyl ester 

Relevant academic research and scientific papers

Natural drug composition modified derivative and anti-tumor application thereof

The invention discloses a camptothecin derivative I and a synthesis method thereof in the field of new drug design and synthesis. The structural formula of the camptothecin derivative I is as shown inthe specification, R in the formula I is selected from H, Br or dehydrogenation, and R1 is selected from C1-C3 alkyl, naphthenic base, benzyl and substituted benzyl. Activity tests prove that the designed and synthesized camptothecin derivative I has excellent anti-tumor effects and particularly is high in liver cancer, stomach cancer, colon cancer and pancreatic cancer activity.

A flow chemistry approach to norcantharidin analogues

Acid-ester and acid-amide norcantharidin derivatives are prepared using a 'one-pot' synthetic procedure utilizing the ThalesNano H-cube flow hydrogenator. Traditionally, rapid library generation and reaction scale up of these analogues was limited by the batch wise hydrogenation of 5,6-dehydronorcantharidin. This was resolved with the use of flow chemistry. With no associated scale up issues, a method was devised to produce norcantharidin, along with acid-ester and acid-amide analogues on any scale necessary for biological screening.

Cantharidin analogues: Synthesis and evaluation of growth inhibition in a panel of selected tumour cell lines

Diels-Alder addition of furans (furan, furfuryl alcohol, and 3-bromofuran) to maelic anhydride yields three distinct 5,6-dehydronorcantharidins. Hydrogenation of (4,10-dioxatricyclo[5.2.1.0]decane-3,5-dione) (4a), in dry ethanol affords the monoester (7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic aid monoethyl ester) (6). Subsequent transesterification affords a series of monoesters (7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acid monomethyl ester (7)), 7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acid monopropyl ester (8), (7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acid monohexyl ester (9)) and differentially substituted diesters (7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2-ethyl ester 3-isopropyl ester) (10), and (7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2-ethyl ester 3-phenyl ester) (11). Analogues were firstly screened for their ability to inhibit protein phosphatases 1 (PP1) and 2A (PP2A) as the lead compounds cantharidin (1) and norcantharidin (2) are known PP1 and PP2A inhibitors. Only analogues 4a, 6-8 displayed good PP1 and PP2A inhibition (PP1 IC50's=2.0, 2.96, 4.71, and 4.82μM, respectively; PP2A IC50's=0.2, 0.45, 0.41, and 0.47μM, respectively). All analogues were also screened for their anti-cancer potential against a panel of tumour cell lines, HL60, L1210, SW480, WiDr, HT29, HCT116, A2780, ADDP, and 143B, producing GI50 values ranging from 6μM to >1000μM. Analogues possessing good PP1 and/or PP2A inhibition also returned moderate to good anti-cancer activity. Analogues with substituents directly attached to the intact bicyclo[2.2.1]heptane skeleton were poor to moderate anti-cancer agents. This correlates well with their lack of PP1 or PP2A activity. Analogues capable of undergoing a facile ring opening of the anhydride or with a single carboxylate were good PP1 and PP2A inhibitors, largely correlating to the observed anti-cancer activity in all cases, except 11. Analogue 11, whist neither a PP1 nor a PP2A inhibitor shows anti-cancer activity comparable to 1 and 2. We believe that intracellular esterases generate the corresponding dicarboxylate, which is a potent PP1 and PP2A inhibitor, and that it is this species which is responsible for the observed anti-cancer activity.

[4 + 2] Cycloadditions of rigid s-cis dienes to C60. A synchronous Diels-Alder reaction

(Matrix presented) The Diels-Alder reaction of rigid s-cis dienes with C60 occurs by a concerted mechanism, via a symmetrical transition state.

Anhydride modified cantharidin analogues: Synthesis, inhibition of protein phosphatases 1 and 2A and anticancer activity

Two series of anhydride modified cantharidin analogues were synthesised and screened for their phosphatase inhibition (PP1 and PP2A) and cytotoxicity in various cancer cell lines (Ovarian A2780, ADDP; Osteosarcoma 143B; and Colon HCT116 and HT29). One series was synthesised by a novel, high yielding one-pot hydrogenation-ring-opening-esterification procedure, the other by acid catalysed acetal formation. Analogues 5-7 and 9 displayed moderate PP2A selectivity (ca. 5- to 20-fold) and inhibition typically in the low μM range (comparable, in some cases to cantharidin). The anticancer activity of these analogues varied with the cell line under study; however, many of them showed selective cytotoxicity for the colon tumour cell lines. (C) 2000 Elsevier Science Ltd. All rights reserved.