3999-55-1Relevant articles and documents
ALKYLBORONIC ACIDS AS ARGINASE INHIBITORS
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Page/Page column 99-100, (2020/08/22)
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.
Catalytic cyclopropanation of electron deficient alkenes mediated by chiral and achiral sulfides: Scope and limitations in reactions involving phenyldiazomethane and ethyl diazoacetate
Aggarwal, Varinder K.,Smitha, Helen W.,Hynd, George,Jones, Ray V.H.,Fieldhouse, Robin,Spey, Sharon E.
, p. 3267 - 3276 (2007/10/03)
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.
Synthesis and antiherpetic activity of (±)-9-[[(Z)-2-(hydroxymethyl)cyclopropyl]methyl]guanine and related compounds
Ashton,Canning Meurer,Cantone,Field,Hannah,Karkas,Liou,Patel,Perry,Wagner,Walton,Tolman
, p. 2304 - 2315 (2007/10/02)
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.