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Synthesis and antibacterial activity of pentacyclines: a novel class of tetracycline analogs.

Sun C, Hunt DK, Clark RB, Lofland D, O'Brien WJ, Plamondon L, Xiao XY - J. Med. Chem. (2011)

Bottom Line: Employing a highly efficient total synthesis approach, we synthesized and evaluated for antibacterial activity diverse and novel pentacycline analogs with systematic variations at C7, C8, C9, and C10.Certain substitution groups, as well as substitution patterns at various positions, were found to be preferred for increased antibacterial activity.A number of pentacycline analogs displayed potent activity in vitro and in vivo, especially against Gram-positive organisms.

View Article: PubMed Central - PubMed

Affiliation: Tetraphase Pharmaceuticals, Watertown, MA 02472, USA.

ABSTRACT
Employing a highly efficient total synthesis approach, we synthesized and evaluated for antibacterial activity diverse and novel pentacycline analogs with systematic variations at C7, C8, C9, and C10. Certain substitution groups, as well as substitution patterns at various positions, were found to be preferred for increased antibacterial activity. A number of pentacycline analogs displayed potent activity in vitro and in vivo, especially against Gram-positive organisms. Several analogs have also shown promising oral bioavailability in rats and cynomolgus monkey.

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Related in: MedlinePlus

Synthesis of 7-(2-Aminoethoxy)-10-azetidinomethyl Pentacycline AnalogsReagents: (a) OsO4, NMO, H2O, THF; (b) NaIO4, H2O, THF; (c) RR′NH, Na(OAc)3BH, HOAc, 1,2-dichloroethane; (d) aq HF, CH3CN; (e) H2, Pd–C, CH3OH.
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sch4: Synthesis of 7-(2-Aminoethoxy)-10-azetidinomethyl Pentacycline AnalogsReagents: (a) OsO4, NMO, H2O, THF; (b) NaIO4, H2O, THF; (c) RR′NH, Na(OAc)3BH, HOAc, 1,2-dichloroethane; (d) aq HF, CH3CN; (e) H2, Pd–C, CH3OH.


Synthesis and antibacterial activity of pentacyclines: a novel class of tetracycline analogs.

Sun C, Hunt DK, Clark RB, Lofland D, O'Brien WJ, Plamondon L, Xiao XY - J. Med. Chem. (2011)

Synthesis of 7-(2-Aminoethoxy)-10-azetidinomethyl Pentacycline AnalogsReagents: (a) OsO4, NMO, H2O, THF; (b) NaIO4, H2O, THF; (c) RR′NH, Na(OAc)3BH, HOAc, 1,2-dichloroethane; (d) aq HF, CH3CN; (e) H2, Pd–C, CH3OH.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3108469&req=5

sch4: Synthesis of 7-(2-Aminoethoxy)-10-azetidinomethyl Pentacycline AnalogsReagents: (a) OsO4, NMO, H2O, THF; (b) NaIO4, H2O, THF; (c) RR′NH, Na(OAc)3BH, HOAc, 1,2-dichloroethane; (d) aq HF, CH3CN; (e) H2, Pd–C, CH3OH.
Bottom Line: Employing a highly efficient total synthesis approach, we synthesized and evaluated for antibacterial activity diverse and novel pentacycline analogs with systematic variations at C7, C8, C9, and C10.Certain substitution groups, as well as substitution patterns at various positions, were found to be preferred for increased antibacterial activity.A number of pentacycline analogs displayed potent activity in vitro and in vivo, especially against Gram-positive organisms.

View Article: PubMed Central - PubMed

Affiliation: Tetraphase Pharmaceuticals, Watertown, MA 02472, USA.

ABSTRACT
Employing a highly efficient total synthesis approach, we synthesized and evaluated for antibacterial activity diverse and novel pentacycline analogs with systematic variations at C7, C8, C9, and C10. Certain substitution groups, as well as substitution patterns at various positions, were found to be preferred for increased antibacterial activity. A number of pentacycline analogs displayed potent activity in vitro and in vivo, especially against Gram-positive organisms. Several analogs have also shown promising oral bioavailability in rats and cynomolgus monkey.

Show MeSH
Related in: MedlinePlus