635758-46-2Relevant academic research and scientific papers
Chemoenzymatic Total Synthesis and Structural Diversification of Tylactone-Based Macrolide Antibiotics through Late-Stage Polyketide Assembly, Tailoring, and C-H Functionalization
Lowell, Andrew N.,Demars, Matthew D.,Slocum, Samuel T.,Yu, Fengan,Anand, Krithika,Chemler, Joseph A.,Korakavi, Nisha,Priessnitz, Jennifer K.,Park, Sung Ryeol,Koch, Aaron A.,Schultz, Pamela J.,Sherman, David H.
supporting information, p. 7913 - 7920 (2017/06/20)
Polyketide synthases (PKSs) represent a powerful catalytic platform capable of effecting multiple carbon-carbon bond forming reactions and oxidation state adjustments. We explored the functionality of two terminal PKS modules that produce the 16-membered tylosin macrocycle, using them as biocatalysts in the chemoenzymatic synthesis of tylactone and its subsequent elaboration to complete the first total synthesis of the juvenimicin, M-4365, and rosamicin classes of macrolide antibiotics via late-stage diversification. Synthetic chemistry was employed to generate the tylactone hexaketide chain elongation intermediate that was accepted by the juvenimicin (Juv) ketosynthase of the penultimate JuvEIV PKS module. The hexaketide is processed through two complete modules (JuvEIV and JuvEV) in vitro, which catalyze elongation and functionalization of two ketide units followed by cyclization of the resulting octaketide into tylactone. After macrolactonization, a combination of in vivo glycosylation, selective in vitro cytochrome P450-mediated oxidation, and chemical oxidation was used to complete the scalable construction of a series of macrolide natural products in as few as 15 linear steps (21 total) with an overall yield of 4.6%.
Synthesis and biological activity of enantiomeric pairs of 5-(alk-2-enyl)thiolactomycin and 5-[(E)-cycloalk-2-enylidenemethyl] thiolactomycin congeners
Ohata, Kohei,Terashima, Shiro
experimental part, p. 920 - 936 (2010/03/23)
The title compounds were synthesized by the efficient route previously explored for the synthesis of enantiomeric pairs of thiolactomycin and its 3-demethyl derivative. These studies were carried out to prove the flexibility of the previously explored synthetic route to natural thiolactomycin (TLM) 1 and to examine the structure-activity relationship on the 5-position of 1. While all of the synthesized congeners lacked in vitro antibacterial activity, these studies led us to find 5-(alk-2-enyl)-TLM (ent-4d) which exhibits mammalian type I fatty acid synthase (FAS) inhibitory activity equal to that of C75, a potent inhibitor reported previously. It was also found that 5-[(E)-cycloalk-2- enylidenemethyl]-TLM (ent-5c) exhibited slightly less potent mammalian type I FAS inhibitory activity than C75.
Synthesis and biological activity of enantiomeric pairs of 5-vinylthiolactomycin congeners
Ohata, Kohei,Terashima, Shiro
, p. 4070 - 4074 (2008/02/07)
Twelve enantiomeric pairs of 5-vinylthiolactomycin congeners were synthesized by employing our efficient synthetic route previously explored for the synthesis of enantiomeric pairs of thiolactomycin and its 3-demethyl derivative. From the biological activ
2-OXAZOLIDINONES AND THEIR USE AS INHIBITORS OF ANIMAL CELL MOTILITY AND GROWTH
-
Page 53; 61, (2010/11/30)
Cell motility and growth inhibitors, including compounds of the general structural formula (I), and use of the cell motility and cell growth inhibitors, and pharmaceutically acceptable salts, pro-drugs, and solvates thereof, as therapeutic agents, are disclosed.
