1.Combined crossed molecular beam and ab initio investigation of the multichannel reaction of boron monoxide (BO; X2Σ+) with Propylene (CH3CHCH2; X1A'): competing atomic hydrogen and methyl loss pathways.
Maity S1, Dangi BB, Parker DS, Kaiser RI, An Y, Sun BJ, Chang AH. J Phys Chem A. 2014 Oct 16;118(41):9632-45. doi: 10.1021/jp507001r. Epub 2014 Oct 3.
The reaction dynamics of boron monoxide ((11)BO; X(2)Σ(+)) with propylene (CH(3)CHCH(2); X(1)A') were investigated under single collision conditions at a collision energy of 22.5 ± 1.3 kJ mol(-1). The crossed molecular beam investigation combined with ab initio electronic structure and statistical (RRKM) calculations reveals that the reaction follows indirect scattering dynamics and proceeds via the barrierless addition of boron monoxide radical with its radical center located at the boron atom. This addition takes place to either the terminal carbon atom (C1) and/or the central carbon atom (C2) of propylene reactant forming (11)BOC(3)H(6) intermediate(s). The long-lived (11)BOC(3)H(6) doublet intermediate(s) underwent unimolecular decomposition involving at least three competing reaction mechanisms via an atomic hydrogen loss from the vinyl group, an atomic hydrogen loss from the methyl group, and a methyl group elimination to form cis-/trans-1-propenyl-oxo-borane (CH(3)CHCH(11)BO), 3-propenyl-oxo-borane (CH(2)CHCH(2)(11)BO), and ethenyl-oxo-borane (CH(2)CH(11)BO), respectively.
2.Generation and electrophile trapping of N-Boc-2-lithio-2-azetine: synthesis of 2-substituted 2-azetines.
Hodgson DM1, Pearson CI, Kazmi M. Org Lett. 2014 Feb 7;16(3):856-9. doi: 10.1021/ol403626k. Epub 2014 Jan 10.
s-BuLi-induced α-lithiation-elimination of LiOMe from N-Boc-3-methoxyazetidine and further in situ α-lithiation generates N-Boc-2-lithio-2-azetine which can be trapped with electrophiles, either directly (carbonyl or heteroatom electrophiles) or after transmetalation to copper (allowing allylations and propargylations), providing a concise access to 2-substituted 2-azetines.
3.Inhibitor mediated protein degradation.
Long MJ1, Gollapalli DR, Hedstrom L. Chem Biol. 2012 May 25;19(5):629-37. doi: 10.1016/j.chembiol.2012.04.008.
The discovery of drugs that cause the degradation of their target proteins has been largely serendipitous. Here we report that the tert-butyl carbamate-protected arginine (Boc(3)Arg) moiety provides a general strategy for the design of degradation-inducing inhibitors. The covalent inactivators ethacrynic acid and thiobenzofurazan cause the specific degradation of glutathione-S-transferase when linked to Boc(3)Arg. Similarly, the degradation of dihydrofolate reductase is induced when cells are treated with the noncovalent inhibitor trimethoprim linked to Boc(3)Arg. Degradation is rapid and robust, with 30%-80% of these abundant target proteins consumed within 1.3-5 hr. The proteasome is required for Boc(3)Arg-mediated degradation, but ATP is not necessary and the ubiquitin pathways do not appear to be involved. These results suggest that the Boc(3)Arg moiety may provide a general strategy to construct inhibitors that induce targeted protein degradation.
4.Characterization of in vitro metabolites of TM-2, a potential antitumor drug, in rat, dog and human liver microsomes using liquid chromatography/tandem mass spectrometry.
Men L1, Zhao Y, Lin H, Yang M, Liu H, Tang X, Yu Z. Rapid Commun Mass Spectrom. 2014 Oct 30;28(20):2162-70. doi: 10.1002/rcm.7003.
RATIONALE: TM-2 (13-(N-Boc-3-i-butylisoserinoyl-4,10-β-diacetoxy-2-α-benzoyloxy-5-β,20-epoxy-1,13-α-dihydroxy-9-oxo-19-norcyclopropa[g]tax-11-ene) is a novel semi-synthetic taxane derivative. Our previous study demonstrated that it is a promising taxane derivative. The in vitro comparative metabolic profile of a drug between animals and humans is a key issue that should be investigated at early stages of drug development to better select drug candidates. In this study, the in vitro metabolic pathways of TM-2 in rat, dog and human liver microsomes were established and compared.
