Phthalides and Phthalans: Synthetic Methodologies and Their Applications in the Total Synthesis

Complex antibiotics based on natural products are almost invariably prepared by semisynthesis, or chemical transformation of the isolated natural products. This approach greatly limits the range of accessible structures that might be studied as new antibiotic candidates. Here we report a short and enantioselective synthetic route to a diverse range of 6-deoxytetracycline antibiotics. The common feature of this class is a scaffold of four linearly fused rings, labeled A through D. We targeted not a single compound but a group of structures with the D ring as a site of structural variability. A late-stage, diastereoselective C-ring construction was used to couple structurally varied D-ring precursors with an AB precursor containing much of the essential functionality for binding to the bacterial ribosome. Five derivatives were synthesized from benzoic acid in yields ranging from 5 to 7% over 14 to 15 steps, and a sixth, (-)-doxycycline, was synthesized in 8.3% yield over 18 steps.

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A convergent enantioselective route to structurally diverse 6-deoxytetracycline antibiotics

Structure, synthesis, and chemical reactions of fluorinated cyclopropanes and cyclopropenes.

Recent trends in the synthesis of carbazoles: an update

Oxidative weathering of Illinois No.6 coal

New synthetic methods for the regioselective annelation of aromatic rings: 1-hydroxy-2,3-disubstituted naphthalenes and 1,4-dihydroxy-2,3-disubstituted naphthalenes

Anthra[1,2-b]pyran antibiotics: total synthesis of O-methylkidamycinone

4H-Anthra[1,2-b]pyran antibiotics. Total synthesis of the methyl ether of kidamycinone

New synthetic strategy for the preparation of linear phenolic natural products

ortho-Toluate Carbanion Chemistry: Sulfenylation and Selenation

Richard P. Rhee

Papers

New synthetic methods for the regioselective annelation of aromatic rings: 1-hydroxy-2,3-disubstituted naphthalenes and 1,4-dihydroxy-2,3-disubstituted naphthalenes

Anthra[1,2-b]pyran antibiotics: total synthesis of O-methylkidamycinone

4H-Anthra[1,2-b]pyran antibiotics. Total synthesis of the methyl ether of kidamycinone

New synthetic strategy for the preparation of linear phenolic natural products

ortho-Toluate Carbanion Chemistry: Sulfenylation and Selenation