- ALKYLBORONIC ACIDS AS ARGINASE INHIBITORS
-
Provided are alkylboronic acids as arginase inhibitors represented by formula (I), or a pharmaceutically acceptable salt, stereoisomer, tautomer, or prodrug thereof and a pharmaceutical composition comprising said compounds.
- -
-
Page/Page column 99-100
(2020/08/22)
-
- A convenient chemo-enzymatic synthesis and 18F-labelling of both enantiomers of trans-1-toluenesulfonyloxymethyl-2-fluoromethyl-cyclopropane
-
The present report is concerned with a stereoselective, reliable route to trans-1,2-disubstituted cyclopropanes and in particular to (S,S)-1- tosyloxymethyl-2-fluoromethyl-cyclopropane (1) and (R,R)-1-tosyloxymethyl-2- fluoromethyl-cyclopropane (ent-1) as conformationally restricted, terminally fluorinated C4-building blocks for medicinal chemistry. The enzymatic kinetic resolution based synthesis of 1 and ent-1 utilises inexpensive, commercially available starting materials. It is based on enantiomeric resolution of rac-cyclopropane carboxylic esters using esterase from Streptomyces diastatochromogenes. Both enantiomers of 1 were prepared selectively in high overall yield over nine steps, starting from ethyl acrylate. The successful radiosynthesis of [18F]-1 and [18F]-ent-1 is also reported.
- Riss, Patrick Johannes,Roesch, Frank
-
experimental part
p. 4567 - 4574
(2009/03/12)
-
- Catalytic cyclopropanation of electron deficient alkenes mediated by chiral and achiral sulfides: Scope and limitations in reactions involving phenyldiazomethane and ethyl diazoacetate
-
Phenyldiazomethane reacts with electron deficient alkenes in the presence of catalytic amounts of transition metal catalyst [Rh2(OAc)4 was better than Cu(acac)2] and catalytic amounts of sulfide to give cyclopropanes. Pentamethylene sulfide was found to be superior to tetrahydrothiophene and the optimum solvent was toluene. Under these optimised conditions a range of enones were cyclopropanated in high yields. Cyclic enones and acrylates were not successful in this process. The use of the chiral 1,3-oxathiane derived from camphorsulfonyl chloride in 2 steps in this process furnished cyclopropanes in good yield and very high enantiomeric excess (>97% ee). The absolute stereochemistry of cyclopropane 10 was proven by X-ray analysis and the origin of the stereochemical induction has been rationalised. Extension of this work to include diazoesters was partially successful. Again pentamethylene sulfide was found to be superior to tetrahydrothiophene, but this time both Rh2(OAc)4 and Cu(acac)2 were found to be equally effective. Enones, fumarates and unsaturated nitro compounds worked well but simple acrylates and unsaturated aldehydes were not effective substrates. Control experiments were conducted in which the stabilised ylide was isolated and reacted with the less successful substrates and, whilst unsaturated aldehydes still gave low yields, simple acrylates gave high yields of the corresponding cyclopropane. The use of the chiral 1,3-oxathiane was not successful with these more stable diazo compounds.
- Aggarwal, Varinder K.,Smitha, Helen W.,Hynd, George,Jones, Ray V.H.,Fieldhouse, Robin,Spey, Sharon E.
-
p. 3267 - 3276
(2007/10/03)
-
- Synthesis of Cyclopropyl Carbocyclic Nucleosides
-
As representatives of a novel class of carboxylic nucleoside analogues (+/-)-cis-, (-)-cis and (+/-)-trans 9-(2-hydroxymethylcyclopropyl)-adenine (= -methanol) were synthesized from the corresponding dialkyl 1,2-cyclopropane dicarboxylates.
- Csuk, Rene,Scholz, Yvonne von
-
p. 10431 - 10442
(2007/10/02)
-
- Synthesis and antiherpetic activity of (±)-9-[[(Z)-2-(hydroxymethyl)cyclopropyl]methyl]guanine and related compounds
-
A series of analogues of acyclovir and ganciclovir were prepared in which conformational constrainst were imposed by incorporation of a cyclopropane ring or unsaturation into the side chain. In addition, several related base-modified compounds were synthesized. These acyclonucleosides were evaluated for enzymatic phosphorylation and DNA polymerase inhibition in a staggered assay and for inhibitory activity against herpes simplex virus types 1 and 2 in vitro. Certain of the guanine or 8-azaguanine derivatives were good substrates for the viral thymidine kinase and were further converted to triphosphate, but none was a potent inhibitor of the viral DNA polymerase. Nevertheless, one member of this group, (±)-9-[[(Z)-2-(hydroxymethyl)cyclopropyl]methyl]guanine (3a), displayed significant antiherpetic activity in vitro, superior to that of the corresponding cis olefin 4a. Another group, typified by (±)-9-[[(E)-2-(hydroxymethyl)cyclopropyl]methyl]adenine (17b), possessed modest antiviral activity despite an apparent inability to be enzymatically phosphorylated. The relationship of side-chain conformation and flexibility to biological activity in this series is discussed.
- Ashton,Canning Meurer,Cantone,Field,Hannah,Karkas,Liou,Patel,Perry,Wagner,Walton,Tolman
-
p. 2304 - 2315
(2007/10/02)
-
- The Synthesis of a Cyclopropane Amino Acid, trans-α-(Carboxycyclopropyl)glycine, found in Ackee Seed
-
trans-α-(Carboxycyclopropyl)glycine, a constituent of ackee seed (Blighia sapida), has been synthesized via the key intermediate ethyl (E)-4,4-diethoxybut-2-enoate.
- Landor, Stephen R.,Landor, Phyllis, D.,Kalli, Michael
-
p. 2921 - 2926
(2007/10/02)
-
- CYCLOPROPANATION OF DIMETHYL FUMARATE AND MALEATE WITH GEM-DIHALIDES CATALYZED BY Co(0)- OR Ni(0)-COMPLEX AND ZINC.
-
The reaction of bis(acetonitrile)bis(diethyl fumarate)cobalt(0) with dibromomethane gave diethyl trans-1,2-cyclopropanedicarboxylate in a 67% yield based on the cobalt complex. Dimethyl cis-1,2-cyclopropanedicarboxylate was obtained in a 52% yield from the reaction of dimethyl maleate with dibromomethane in the presence of acetonitrilebis(dimethyl maleate)nickel(0) accompanied by the formation of the trans-isomer in a 14% yield. The addition of zinc gave cyclopropanes in over 100% yields based on cobalt or nickel. 3-Methyl- and 3,3-dimethyl-1,2-cyclopropanedicarboxylic acid esters were produced by the reaction of dimethyl fumarate or maleate with 1,1-dibromoethane and 2,2-dibromopropane. The yield in the cobalt catalyst system decreases with an increase of substituents of gem-dibromides, while that in the nickel catalyst system does not vary appreciably.
- Kanai,Nishiguchi,Matsuda
-
p. 1592 - 1597
(2007/10/02)
-