Transition-metal-catalyzed C H functionalization for late-stage modification of peptides and proteins

Lü, Xi; He, Shuai; Cheng, Wan‐Min; Shi, Jing

doi:10.1016/j.cclet.2018.05.011

Cited by 59 publications

(15 citation statements)

References 195 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Catalytic late-stage C-H functionalization, a highly efficient synthetic strategy, is regarded as a crucial tactic in the area of natural products, drug discovery, and medicinal chemistry [7][8][9][10][11][12] as it confers an invaluable synthetic opportunity for the facile diversification of biologically active complex molecules at the late stage. In recent years, much effort has been devoted Scheme 1: Mn-catalyzed late-stage fluorination of sclareolide (1) and complex steroid 3.…”

Section: Introductionmentioning

confidence: 99%

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

Son¹

2021

Beilstein J. Org. Chem.

View full text Add to dashboard Cite

The late-stage C–H functionalization of bioactive structural motifs is a powerful synthetic strategy for accessing advanced agrochemicals, bioimaging materials, and drug candidates, among other complex molecules. While traditional late-stage diversification relies on the use of precious transition metals, the utilization of 3d transition metals is an emerging approach in organic synthesis. Among the 3d metals, manganese catalysts have gained increasing attention for late-stage diversification due to the sustainability, cost-effectiveness, ease of operation, and reduced toxicity. Herein, we summarize recent manganese-catalyzed late-stage C–H functionalization reactions of biologically active small molecules and complex peptides.

show abstract

Section: Introductionmentioning

confidence: 99%

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

Son¹

2021

Beilstein J. Org. Chem.

View full text Add to dashboard Cite

show abstract

“…Among the limited methods to functionalize the benzene portion of indole, functionalization at C4 and C7 typically rely on coordination of the catalyst to specific directing groups installed on either C3 or N1, respectively [13][14][15]. However, this method suffers from low functional group tolerance and a limited substrate scope [14][15][16][17][18][19][20][21][22]. The few described methods for C5 and C6 indole functionalization provide limited functional group tolerance [19,23].…”

Section: Introductionmentioning

confidence: 99%

Indole C6 Functionalization of Tryprostatin B Using Prenyltransferase CdpNPT

et al. 2020

View full text Add to dashboard Cite

Tryprostatin A and B are prenylated, tryptophan-containing, diketopiperazine natural products, displaying cytotoxic activity through different mechanisms of action. The presence of the 6-methoxy substituent on the indole moiety of tryprostatin A was shown to be essential for the dual inhibition of topoisomerase II and tubulin polymerization. However, the inability to perform late-stage modification of the indole ring has limited the structure–activity relationship studies of this class of natural products. Herein, we describe an efficient chemoenzymatic approach for the late-stage modification of tryprostatin B using a cyclic dipeptide N-prenyltransferase (CdpNPT) from Aspergillus fumigatus, which generates novel analogs functionalized with allylic, benzylic, heterocyclic, and diene moieties. Notably, this biocatalytic functionalizational study revealed high selectivity for the indole C6 position. Seven of the 11 structurally characterized analogs were exclusively C6-alkylated, and the remaining four contained predominant C6-regioisomers. Of the 24 accepted substrates, 10 provided >50% conversion and eight provided 20–50% conversion, with the remaining six giving <20% conversion under standard conditions. This study demonstrates that prenyltransferase-based late-stage diversification enables direct access to previously inaccessible natural product analogs.

show abstract

“…Recently, transition metal catalyzed-regioselective C-H bond functionalization has emerged as a suitable method to build-up a library of compounds in a minimum of steps. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Few methods have been dedicated to the late-stage modification of antipyrine. In 2013, Kwang and co-workers reported the first example of C4 modification of antipyrine using Pd-catalyzed C-H bond alkenylation using activated alkenes (Figure 2a).…”

Section: Introductionmentioning

confidence: 99%

Reactivity of antipyrine and haloantipyrines in Pd-catalyzed C H bond arylations

Sasmal

Bera

Doucet

et al. 2020

Tetrahedron Letters

View full text Add to dashboard Cite

We reported herein the Pd-catalyzed direct arylation of antipyrine using Pd(OAc) 2 as catalyst associated with KOAc as inexpensive base. In most cases, diethyl carbonate was used a sustainable solvent. The reaction tolerated a wide range of functional groups on the aryl bromide partners (e.g., nitrile, nitro, chloro, fluoro, formyl, acetyl, propionyl, benzoyl, ester, methyl, methoxy). In addition, some nitrogen-containing heteroaryl bromides were also efficiently coupled with antipyrine. We also demonstrated that in contrast to 4-bromoantipyrine, 4-iodoantipyrine could be employed as an efficient heteroaryl source in Pd-catalyzed C-H bond arylation of 5-membered ring heteroarenes.

show abstract

Transition-metal-catalyzed C H functionalization for late-stage modification of peptides and proteins

Cited by 59 publications

References 195 publications

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

Indole C6 Functionalization of Tryprostatin B Using Prenyltransferase CdpNPT

Reactivity of antipyrine and haloantipyrines in Pd-catalyzed C H bond arylations

Contact Info

Product

Resources

About