Asymmetric synthesis of dihydroquinazolinones via directed ortho metalation and addition to tert-butanesulfinyl imines

An asymmetric route to dihydroquinazolinones via the addition of ortho metalated substrates to tert-butanesulfinyl imines is reported. The scope of the nucleophile and electrophile components and the absolute stereochemical outcome are presented.     

Advective flow and floc permeability

This work monitored advection flow through a floc by bubble tracking. Close examination of the motion of a swarm of hydrogen bubbles that passed over a free-falling floc allowed the extent of advection flow to be estimated at 53% for the original activated sludge floc, and 12% for the flocculated floc. The interior permeability of the sludge flocs was estimated from this information. The fluid force exerted on the falling floc was also considered.     

Chemistry of platensimycin

Platensimycin is a novel natural product antibiotic that inhibits bacterial growth by inhibiting fatty acid synthesis specifically inhibiting the elongation condensing enzyme FabF. Reaction with diazomethane at controlled temperatures led to selective methylation of the phenolic groups. Methylation, halogenation, reduction, epoxidation, Bayer-Villiger oxidation and details of the conversion of dihydroplatensimycin to the cyclic enamino-amido forms have been described.     

New members of a class of dinitrosyliron complexes (DNICs): interconversion and spectroscopic discrimination of the anionic {Fe(NO)2}9 [(NO)2Fe(C3H3N2)2]- and [(NO)2Fe(C3H3N2)(SR)]- (C3H3N2 = deprotonated imidazole; R = tBu, Et, Ph)

The anionic {Fe(NO)2}(9) DNIC[(NO)2Fe(C3H3N2)2](-) (2) (C3H3N2 = deprotonated imidazole) containing the deprotonated imidazole-coordinated ligands and DNICs [(NO)2Fe(C3H3N2)(SR)](-) (R = (t)Bu(3), Et(4), Ph(5)) containing the mixed deprotonated imidazole-thiolate coordinated ligands, respectively, were synthesized by thiol protonation or thiolate(s) ligand-exchange reaction. The anionic {Fe(NO)2}(9) DNICs 2- 5 were characterized by IR, UV-vis, EPR, and single-crystal X-ray diffraction. The facile transformation among the anionic {Fe(NO)2}(9) DNICs 2- 5 and [(NO)2Fe(S(t)Bu)2](-)/[(NO)2Fe(SEt)2](-)/[(NO)2Fe(SPh)2](-) was demonstrated in this systematic study. Of importance, the distinct electron-donating ability of thiolates serve to regulate the stability of the anionic {Fe(NO)2}(9) DNICs and the ligand-substitution reactions of DNICs. At 298 K, DNIC 2 exhibits the nine-line EPR signal with g = 2.027 (aN(NO) = 2.20 and aN(Im-H) = 3.15 G; Im-H = deprotonated imidazole) and DNIC 3 displays the nine-line signals with g = 2.027 (aN(NO) = 2.35 and aN(Im-H) = 4.10 G). Interestingly, the EPR spectrum of complex 4 exhibits a well-resolved 11-line pattern with g = 2.027 (aN(NO) = 2.50, aN(Im-H) = 4.10 G, and aH = 1.55 G) at 298 K. The EPR spectra (the pattern of hyperfine splitting) in combination with IR nu NO spectra (DeltanuNO = the separation of NO stretching frequencies, DeltanuNO = approximately 62 cm (-1) for 2 vs approximately 50 cm(-1) for 3- 5 vs approximately 43 cm(-1) for [(NO)2Fe(S(t)Bu)2](-)/[(NO)2Fe(SEt)2](-)/[(NO)2Fe(SPh)2](-)) may serve as an efficient tool for the discrimination of the existence of the anionic {Fe(NO)2}(9) DNICs containing the different ligations [N,N]/[N,S]/[S,S].     

A convenient approach toward the synthesis of enantiopure isomers of DMDP and ADMDP

A practical method for the synthesis of five-membered iminocyclitols, pyrrolidine alkaloids bearing multiple hydroxyl substituents, has been developed. All of the eight key intermediates, enantiopure tri-O-benzyl cyclic nitrones, are prepared from four cheap, readily available d-aldopentoses. The nucleophilic addition of cyclic nitrones with vinyl magnesium chloride and TMSCN shows high 2,3-trans stereoselectivity. To construct the 2,3-cis configurations, inversion of the C-2 nitrile group is achieved via an elimination-reduction sequence. Using this approach, five isomers of DMDP and six isomers of ADMDP are prepared efficiently. In the biological evaluation, iminocyclitol 27 is a new and potent inhibitor against β-hexosaminidase with an IC₅₀ value of 0.2 μM.     

Neuropeptide delivery to the brain: a von Willebrand factor signal peptide to direct neuropeptide secretion

Background  

Multiple neuropeptides, sometimes with opposing functions, can be produced from one precursor gene. To study the roles of the different neuropeptides encoded by one large precursor we developed a method to overexpress minigenes and establish local secretion.