Glen Bigam

Evaluation of Mannich bases of 2-arylidene-1,3-diketones versus murine P388 leukemia

Abstract A number of novel Mannich bases of 2-arylidene-1,3-diketones were shown to have some activity versus P388 lymphocytic leukemia in mice. PMR spectroscopy revealed that most of these compounds underwent intramolecular cyclization in deuterium oxide to give cyclic enols and the ratio of cyclic to acyclic species was probably influenced by steric considerations. Attempts to prepare rigid analogues of the Mannich bases of the acyclic 2-arylidene-1,3-diketones led to a further example of intramolecular cyclization in which dicycloalkano[ b,e ]pyrandiones or alternatively Michael adducts were produced. In general, these latter compounds did not have activity in the P388 leukemia screen.

Schisanlactone B, a new triterpenoid from a Schisandra sp.

Abstract Schisanlactone B, a triterpenoid isolated from a Schisandra sp ., is shown to have structure 2 .

Structure elucidation and conformational analysis of gonadotropin releasing hormone and its novel synthetic analogue [Tyr(OMe)5, d-Lys6, Aze9NHEtGnRH: The importance of aromatic clustering in the receptor binding activity†

Summary The conformational properties of gonadotropin releasing hormone (GnRH) in dimethylsulfoxide- d 6 were investigated by nuclear Overhauser effect (nOe) enhancement studies and were compared with the conformational properties of its analogue [Tyr(OMe) 5 GnRH resulting after methylation of the tyrosine hydroxyl. Assignment of all backbone and side-chain protons was possible by combining information from intraresidue nOe studies with two-dimensional correlated spectroscopy (COSY/TOCSY) studies. Saturation of distinct proton resonances of the three aromatic residues Tyr, His, Trp, in clear areas of the NMR spectrum of GnRH resulted in interresidue enhancements of aromatic resonances indicating the proximity of the three aromatic rings. This spatial proximity is not observed in [Tyr(OMe) 5 ]GnRH and is correlated with a lower receptor binding affinity in the rat pituitary ( K d = 1.53 ± 0.35 × 10 −6 M) compared with that exerted by GnRH ( K d = 3.69 ± 0.89 × 10 −9 M). However, substitution of Gly at position 6 of [Tyr(OMe) 5 ]GnRH with d -Lys 6 and further replacement of Pro at position 9 with the more rigid Aze residue [Tyr(OMe) 5 , d -Lys 6 , Aze 9 NHEt]GnRH significantly improved the binding affinity ( K d = 0.689 ± 10.15 × 10 −9 ) and this may be due to the restoration of the ring cluster. Overall, the clustering of the aromatic rings observed in GnRH was not seen in [Tyr(OMe) 5 ]GnRH and this conformational difference may be responsible for receptor recognition and higher binding of the parent peptide.

Intramolecular cyclization and cytotoxicities of some Mannich bases of styryl ketones

The extent of intramolecular cyclization in a series of Mannich bases derived from 2-arylidene-1,3-diketones (series 5) was probably influenced by the steric and electronic properties of the different basic groups. Replacement of one of the keto groups in series 5 by hydrogen, methyl, carboethoxy and phenyl functions gave series 6 in which the intramolecular cyclization process was abolished. Evaluation of the compounds versus the EMT6 cells in vitro indicated that cytotoxicity did not appear to be influenced by the ratio of cyclic and acyclic species but in series 6 bioactivity was correlated with the electronic nature of the substituents. Two compounds had approximately one-sixth of the activity of the reference compound, melphalan.Abstract The extent of intramolecular cyclization in a series of Mannich bases derived from 2-arylidene-1,3-diketones (series 5 ) was probably influenced by the steric and electronic properties of the different basic groups. Replacement of one of the keto groups in series 5 by hydrogen, methyl, carboethoxy and phenyl functions gave series 6 in which the intramolecular cyclization process was abolished. Evaluation of the compounds versus the EMT6 cells in vitro indicated that cytotoxicity did not appear to be influenced by the ratio of cyclic and acyclic species but in series 6 bioactivity was correlated with the electronic nature of the substituents. Two compounds had approximately one-sixth of the activity of the reference compound, melphalan.

Original paperIntramolecular cyclization and cytotoxicities of some Mannich bases of styryl ketonesCyclisation intramoléculaire et cytotoxicité de quelques bases de Mannich dérivées de styrylcétones

The extent of intramolecular cyclization in a series of Mannich bases derived from 2-arylidene-1,3-diketones (series 5) was probably influenced by the steric and electronic properties of the different basic groups. Replacement of one of the keto groups in series 5 by hydrogen, methyl, carboethoxy and phenyl functions gave series 6 in which the intramolecular cyclization process was abolished. Evaluation of the compounds versus the EMT6 cells in vitro indicated that cytotoxicity did not appear to be influenced by the ratio of cyclic and acyclic species but in series 6 bioactivity was correlated with the electronic nature of the substituents. Two compounds had approximately one-sixth of the activity of the reference compound, melphalan.Abstract The extent of intramolecular cyclization in a series of Mannich bases derived from 2-arylidene-1,3-diketones (series 5 ) was probably influenced by the steric and electronic properties of the different basic groups. Replacement of one of the keto groups in series 5 by hydrogen, methyl, carboethoxy and phenyl functions gave series 6 in which the intramolecular cyclization process was abolished. Evaluation of the compounds versus the EMT6 cells in vitro indicated that cytotoxicity did not appear to be influenced by the ratio of cyclic and acyclic species but in series 6 bioactivity was correlated with the electronic nature of the substituents. Two compounds had approximately one-sixth of the activity of the reference compound, melphalan.

Phase Modulation in APT Spectra for ABX Patterns

Anomalous APT spectra are reported for an organophosphorus compound containing methylene 13C nuclei coupled to two 31P nuclei. Strong coupling effects in these ABX spin systems are shown to account for the anomalous phases and intensities of the APT spectra by density matrix simulations.