539-87-7Relevant articles and documents
Conformations of Oxocane
Meyer, Walter L.,Taylor, Patterson W.,Reed, Scott A.,Leister, Marvin C.,Schneider, Hans-Joerg,et al.
, p. 291 - 298 (1992)
Conformational analysis of oxocane (oxacyclooctane) has been examined by molecular mechanics (MM2), variable-temperature 13C NMR, and lanthanide-induced shift (LIS) 1H and 13C NMR.MM2 calculations find the BC-3 conformer and its enantiomer BC-7 to be favored, with the four next best forms and their energies relative to BC-3-being BC-1 (1.1 kcal/mol), TBC-1(1.1), BC-4(1.5), and TCC-1(1.6).Barriers to pseudorotational interconversion of BC-3 and BC-7 are calculated to be 5.0 kcal/mol through BC-5 and 6.7 kcal/mol through BC-1.The former would allow fast BC-3/BC-7 equilibration even at -170 deg C, which would leave reported low-temperature 1H NMR spectra compatible with a BC-3 structure as well as BC-1.Calculated barriers for BC ring inversion and interconversion of the BC family with the crown family (TCC-1) are 8.2 and 8.5 kcal/mol, respectively.A new two-step synthesis of oxocane and its 2,2,7,7-d4 analogue is reported, the latter allowing unequivocal assignment of chemical shifts. 13C NMR spectra of oxocane between 138 and 290 K show BC-family/crown-family inter-conversion in the vicinity of 215 K (ΔG(excit.) = 10.0 +/- 0.3 kcal/mol), with the crown family comprising 4percent of the equilibrium at 174 K (ΔG0 = 1.1 +/- 0.1 kcal/mol).The 1H and 13C LIS induced by Yb(fod)3 on oxocane agree well with BC-3 and BC-7 being the predominant conformers at room temperature but do not acceptably fit a BC-1 structure.Thus, all available data from calculation and experiment are in accord with BC-3 being the favored conformation of oxocane.
PEGylated Poly-HDACi: A Designer Polyprodrug from Optimized Drug Units**
Han, Jinghua,Huang, Qingqing,Kang, Yanke,Li, Jing,Luo, Zihan,Lv, Wenhui,Meng, Li,Shen, Jie,Wang, Da-Yuan,Wang, Peng George,Wang, Qiuyu,Wang, Yajie,Wang, Yanming
supporting information, (2021/12/22)
We designed, synthesized, and characterized a tri-block copolymer. Its hydrophobic part, a chain of histone deacetylase inhibitor (HDACi) prodrug, was symmetrically flanked by two identical PEG blocks, whereas the built-in HDACi was a linear molecule, terminated with a thiol at one end, and a hydroxyl group at the other. Such a feature facilitated end-to-end linkage of prodrugs through alternatively aligned disulfides and carbonates. The disulfides served dual roles: redox sensors of smart nanomedicine, and warheads of masked HDACi drugs. This approach, carefully designed to benefit both control-release and efficacy, is conceptually novel for optimizing drug units in nanomedicine. Micelles from this designer polyprodrug released only PEG, CO2 and HDACi, and synergized with DOX against HCT116 cells, demonstrating its widespread potential in combination therapy. Our work highlights, for the first time, the unique advantage of thiol-based drug molecules in nanomedicine design.
A Polyketide Cyclase That Forms Medium-Ring Lactones
Gao, De-Wei,Jamieson, Cooper S.,Wang, Gaoqian,Yan, Yan,Zhou, Jiahai,Houk,Tang, Yi
, p. 80 - 84 (2021/01/13)
Medium-ring lactones are synthetically challenging due to unfavorable energetics involved in cyclization. We have discovered a thioesterase enzyme DcsB, from the decarestrictine C1 (1) biosynthetic pathway, that efficiently performs medium-ring lactonizations. DcsB shows broad substrate promiscuity toward linear substrates that vary in lengths and substituents, and is a potential biocatalyst for lactonization. X-ray crystal structure and computational analyses provide insights into the molecular basis of catalysis.
LIPID PRODRUGS OF GLUCOCORTICOIDS AND USES THEREOF
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Paragraph 00544; 00545, (2020/09/12)
The present invention provides lymphatic system-directing lipid prodrugs, pharmaceutical compositions thereof, methods of producing such prodrugs and compositions, and methods of improving the bioavailability or other properties of a therapeutic agent that comprises part of the lipid prodrug. The present invention also provides methods of treating a disease, disorder, or condition such as those disclosed herein, comprising administering to a patient in need thereof a disclosed lipid prodrug or a pharmaceutical composition thereof.
