Trends in applying C–H oxidation to the total synthesis of natural products

Qiu, Yuanyou; Gao, Shuanhu

doi:10.1039/c5np00122f

Cited by 117 publications

(59 citation statements)

References 188 publications

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“…Excellent reviews have summarised approaches like C−H activation used in the synthesis or diversification of natural products ,. In the following chapter, the application of P450 enzymes in diversity‐oriented syntheses is illustrated with some recent examples.…”

Section: Introductionmentioning

confidence: 99%

P450 Monooxygenases Enable Rapid Late‐Stage Diversification of Natural Products via C−H Bond Activation

Fessner

2019

ChemCatChem

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The biological potency of natural products has been exploited for decades. Their inherent structural complexity and natural diversity might hold the key to efficiently address the urgent need for the development of novel pharmaceuticals. At the same time, it is that very complexity, which impedes necessary chemical modifications such as structural diversification, to improve the effectiveness of the drug. For this purpose, Cytochrome P450 enzymes, which possess unique abilities to activate inert sp3‐hybridised C−H bonds in a late‐stage fashion, offer an attractive synthetic tool. In this review the potential of cytochrome P450 enzymes in chemoenzymatic lead diversification is illustrated discussing studies reporting late‐stage functionalisations of natural products and other high‐value compounds. These enzymes were proven to extend the synthetic toolbox significantly by adding to the flexibility and efficacy of synthetic strategies of natural product chemists, and scientists of other related disciplines.

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Section: Introductionmentioning

confidence: 99%

P450 Monooxygenases Enable Rapid Late‐Stage Diversification of Natural Products via C−H Bond Activation

Fessner

2019

ChemCatChem

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“…PTs occur usually in a heterogeneous manner in nature, with the structural diversity being greatly augmented by post-modifications on the basic pentacyclic skeletons, including especially the enzymatic C-H bond oxidation and O-glycosylation 5,6 . With the emergence of new C-H bond oxidation methodologies [7][8][9][10][11] , a new stage is to set for chemical diversification of the naturally abundant PT feedstocks 12,13 , such as oleanolic acid, which are always at low oxidation states.…”

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confidence: 99%

Site-selective C-H hydroxylation of pentacyclic triterpenoids directed by transient chiral pyridine-imino groups

Bian

Zhu

et al. 2020

Nat Commun

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Pentacyclic triterpenoids (PTs) constitute one of the biggest families of natural products, many with higher oxidation state at the D/E rings possess a wide spectrum of biological activties but are poorly accessible. Here we report a site-selective C-H hydroxylation at the D/E rings of PTs paving a way toward these important natural products. We find that Schönecker and Baran's Cu-mediated aerobic oxidation can be applied and become siteselective on PT skeletons, as being effected unexpectedly by the chirality of the transient pyridine-imino directing groups. To prove the applicability, starting from the most abundant triterpenoid feedstock oleanane, three representative saponins bearing hydroxyl groups at C16 or C22 are expeditiously synthesized, and barringtogenol C which bears hydroxyl groups at C16, C21, and C22 is synthesized via a sequential hydroxylation as the key steps.

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“…[1] Nowadays, the benchmark of oxidation chemistry is represented by the functionalization of C(sp 3 )ÀHb onds. [2] This is due to:1 )their poor reactivity, 2) the presence of different CÀHb onds within am olecule, or 3) other functional groups pronet oo xidation. However, CÀH bond oxidations can be selectively differentiated based on their electronic, stereoelectronic,a nd steric features, with very high selectivities.…”

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confidence: 99%

Heterolytic (2 e) vs Homolytic (1 e) Oxidation Reactivity: N−H versus C−H Switch in the Oxidation of Lactams by Dioxirans

Annese

D’Accolti

Fusco

et al. 2016

Chemistry A European J

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Dioxiranes are powerful oxidants that can act via two different mechanisms: 1) homolytic (H abstraction and oxygen rebound) and 2) heterolytic (electrophilic oxidation). So far, it has been reported that the nature of the substrate dictates the reaction mode independently from the dioxirane employed. Herein, we report an unprecedented case in which the nature of the dioxirane rules the oxidation chemoselectivity. In particular, a switch from C-H to N-H oxidation is observed in the oxidation of lactams moving from dimethyl dioxirane (DDO) to methyl(trifluoromethyl)dioxirane (TFDO). A physical organic chemistry study, which combines the oxidation with two other dioxiranes methyl(fluoromethyl)dioxirane, MFDO, and methyl(difluoromethyl)dioxirane, DFDO, with computational studies, points to a diverse ability of the dioxiranes to either stabilize the homo or the heterolytic pathway.

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Trends in applying C–H oxidation to the total synthesis of natural products

Cited by 117 publications

References 188 publications

P450 Monooxygenases Enable Rapid Late‐Stage Diversification of Natural Products via C−H Bond Activation

P450 Monooxygenases Enable Rapid Late‐Stage Diversification of Natural Products via C−H Bond Activation

Site-selective C-H hydroxylation of pentacyclic triterpenoids directed by transient chiral pyridine-imino groups

Heterolytic (2 e) vs Homolytic (1 e) Oxidation Reactivity: N−H versus C−H Switch in the Oxidation of Lactams by Dioxirans

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