CCHF Research | Late-Stage C–H Functionalization
Led by Mo Movassaghi and David Sherman
Nature is capable of generating a vast array of complex molecules for use as signaling and defense agents. One of the most remarkable transformations in biosynthesis is the use of P450 enzymes that have evolved with natural product biosynthetic systems for late stage modification and structure diversification. Nature’s ability to induce C–H functionalization, often C–H oxidation, within complex settings creates opportunities for new bond formations and disconnections at sites that are otherwise chemically inert.
The ability to induce site-specific reactivity on a given molecules at otherwise unreactive sites in complex settings has tremendous significance to the field of complex molecule synthesis. Inspired by natures approach in related processes, a large and important aspect of the center’s efforts are directed at developing modified ezymatic oxidation catalysts that may be used in conjunction with anchoring substrates to provide controlled oxidation and functionalization.
Related Publications:
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03/2018
Structural basis of the Cope rearrangement and cyclization in hapalindole biogenesis
RESEARCH
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01/2018
Cyanthiwigin Natural Product Core as a Complex Molecular Scaffold for Comparative Late-Stage C–H Functionalization Studies
RESEARCH
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11/2017
Synthesis of Diverse 11- and 12-Membered Macrolactones from a Common Linear Substrate Using a Single Biocatalyst
RESEARCH
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07/2017
Enantioselective Total Synthesis of Nigelladine A via Late-Stage C–H Oxidation Enabled by an Engineered P450 Enzyme
RESEARCH
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03/2017
Decoding cyclase-dependent assembly of hapalindole and fischerindole alkaloids
RESEARCH
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10/2016
A Second-Generation Synthesis of the Cyanthiwigin Natural Product Core
RESEARCH
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08/2016
Concise Total Syntheses of (+)-Haplocidine and (+)-Haplocine via Late-Stage Oxidation of (+)-Fendleridine Derivatives
RESEARCH
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07/2016
Biochemical and Structural Characterization of MycCI, a Versatile P450 Biocatalyst from the Mycinamicin Biosynthetic Pathway
RESEARCH
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02/2016
Directed evolution of RebH for catalyst-controlled halogenation of indole C–H bonds
RESEARCH
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12/2015
Hapalindole/Ambiguine Biogenesis Is Mediated by a Cope Rearrangement, C–C Bond-Forming Cascade
RESEARCH
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09/2015
The medicinal chemist's toolbox for late stage functionalization of drug-like molecules
RESEARCH
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08/2015
Concise Total Synthesis of (+)-Luteoalbusins A and B
RESEARCH
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07/2015
Chemotherapeutic natural product ET-743
RESEARCH
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06/2015
Enzymatic hydroxylation of an unactivated methylene C–H bond guided by molecular dynamics simulations
RESEARCH
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01/2015
Late-stage C–H functionalization of complex alkaloids and drug molecules via intermolecular rhodium-carbenoid insertion
RESEARCH
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07/2014
Pd(II)-Catalyzed meta-C–H Olefination, Arylation, and Acetoxylation of Indolines Using a U-Shaped Template
RESEARCH
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10/2013
Profound Methyl Effects in Drug Discovery and a Call for New C–H Methylation Reactions
RESEARCH
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09/2013
Application of diazene-directed fragment assembly to the total synthesis and stereochemical assignment of (+)-desmethyl-meso-chimonanthine and related heterodimeric alkaloids
RESEARCH
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06/2013
C-H Functionalization Logic Enables a Synthesis of (+)-Hongoquercin A and Related Compounds
RESEARCH
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11/2012
Cafestol to Tricalysiolide B and Oxidized Analogues: Biosynthetic and Derivatization Studies Using Non-heme Iron Catalyst Fe(PDP)
RESEARCH
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04/2011
Divergent C–H Functionalizations Directed by Sulfonamide Pharmacophores: Late-Stage Diversification as a Tool for Drug Discovery
RESEARCH