Mimicking Halimane Synthases: Monitoring a Cascade of Cyclizations and Rearrangements from Epoxypolyprenes

Moral, José F. Quı́lez del; Domingo, Victoriano; Pérez, Álvaro; Martínez, Kevin A.; Enríquez, Lourdes; Jaraı́z, M.; López-Pérez, Jose Luis; Barrero, Alejandro F.

doi:10.1021/acs.joc.9b01996

Cited by 4 publications

(5 citation statements)

References 81 publications

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“…48 The 36% yield of tricyclic product 52 was substantially higher than the outcomes from various Lewis acid-promoted transformations. [49][50][51][52][53] The formation of compound 52 is consistent with a mechanism involving concerted cyclization of the three alkenes closest to the epoxide, thereby generating a tertiary carbenium ion 51. The authors proposed that the cations -including protonated epoxide and the tricyclic intermediate cation 51 -were stabilized by the nonnucleophilic solvent HFIP and/or the non-nucleophilic tetrafluoroborate anions.…”

Section: Intramolecular Carbon-carbon Bond-forming Reactionssupporting

confidence: 54%

Fluorinated alcohols: powerful promoters for ring-opening reactions of epoxides with carbon nucleophiles

Dover¹,

McDonald²

2021

Arkivoc

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Ring-opening reactions of epoxides with carbon nucleophiles are valuable transformations for constructing functionalized carbon-carbon bonds. Epoxide ring-opening methods typically require Lewis acidic additives and/or strong nucleophiles to overcome the activation barrier for these reactions. Fluorinated alcohol solvents present a desirable alternative, enhancing the efficacy of these reactions with weak and neutral carbon nucleophiles by promoting electrophilic activation of the epoxide. We present here a thorough review of the literature regarding epoxide ring-opening reactions with carbon nucleophiles in fluorinated alcohol solvents, concluding with a few recent examples with aziridines.

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Section: Intramolecular Carbon-carbon Bond-forming Reactionssupporting

confidence: 54%

Fluorinated alcohols: powerful promoters for ring-opening reactions of epoxides with carbon nucleophiles

Dover¹,

McDonald²

2021

Arkivoc

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“…In this line, the development of new therapies for the inhibition of the virulence factor (VC) formation such as tuberculosinol, 1, and isotuberculosinol, 2, (13R and 13S) is of special interest, where these two halimanes show the main interest and projection. The structures of 1 and 2 have been confirmed by synthesis [29,33,77], enabling researchers to achieve a structural revision of the diterpenes isolated from M. tuberculosis, assigning to isotuberculosinol the same structure of nosyberkol, 2, (isolated from Raspailia sp).…”

Section: Synthesis Of Tuberculosinol 1 and Isotuberculosinolmentioning

confidence: 87%

“…The synthesis of 26 and 27 was carried out by Ohba and co-workers [53], starting with (+)-trans-dihydrocarvone, 46, allowing them to establish the absolute configuration of both natural products. The authors previously developed a reaction sequence similar to that done for the racemic (±)-agelasimine A and (±)-agelasimine B [76,77]. The asymmetric synthesis of (+)-agelasimine A, 26, and (+)-agelasimine B, 27, was done from (+)-trans- (Figure 7).…”

Section: Synthesis Of (+)-Agelasimine a 26 And (+)-Agelasimine B 27mentioning

confidence: 99%

Antibacterial Natural Halimanes: Potential Source of Novel Antibiofilm Agents

et al. 2020

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The development of new agents against bacteria is an urgent necessity for human beings. The structured colony of bacterial cells, called the biofilm, is used to defend themselves from biocide attacks. For this reason, it is necessary to know their structures, develop new agents to eliminate them and to develop new procedures that allow an early diagnosis, by using biomarkers. Among natural products, some derivatives of diterpenes with halimane skeleton show antibacterial activity. Some halimanes have been isolated from marine organisms, structurally related with halimanes isolated from Mycobacterium tuberculosis. These halimanes are being evaluated as virulence factors and as tuberculosis biomarkers, this disease being one of the major causes of mortality and morbidity. In this work, the antibacterial halimanes will be reviewed, with their structural characteristics, activities, sources and the synthesis known until now.

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“…3(c). Compound 1s was chemically synthesized before and its 2,3‐epoxy moiety could be initiated for cyclization in a way similar to 2,3‐oxidosqualene by Lewis acid either chemically or enzymatically to form pentacyclic triterpenes (Van Tamelen et al ., 1972; Horan et al ., 1973; Domingo et al ., 2012; Quilez del Moral et al ., 2019). However, compound 1s has never been isolated in nature or as enzymatic product before.…”

Section: Resultsmentioning

confidence: 99%

Insight into neofunctionalization of 2,3‐oxidosqualene cyclases in B,C‐ring‐opened triterpene biosynthesis in quinoa

Zhou,

Sun,

Xiong

et al. 2023

New Phytologist

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Summary Bioactive triterpenes feature complex fused‐ring structures, primarily shaped by the first‐committed enzyme, 2,3‐oxidosqualene cyclases (OSCs) in plant triterpene biosynthesis. Triterpenes with B,C‐ring‐opened skeletons are extremely rare with unknown formation mechanisms, harbouring unchartered chemistry and biology. Here, through mining the genome of Chenopodium quinoa followed by functional characterization, we identified a stress‐responsive and neofunctionalized OSC capable of generating B,C‐ring‐opened triterpenes, including camelliol A and B and the novel (−)‐quinoxide A as wax components of the specialized epidermal bladder cells, namely the quinoxide synthase (CqQS). Protein structure analysis followed by site‐directed mutagenesis identified key variable amino acid sites underlying functional interconversion between pentacyclic β‐amyrin synthase (CqbAS1) and B,C‐ring‐opened triterpene synthase CqQS. Mutation of one key residue (N612K) in even evolutionarily distant Arabidopsis β‐amyrin synthase could generate quinoxides, indicating a conserved mechanism for B,C‐ring‐opened triterpene formation in plants. Quantum computation combined with docking experiments further suggests that conformations of conserved W613 and F413 of CqQS might be key to selectively stabilizing intermediate carbocations towards B,C‐ring‐opened triterpene formation. Our findings shed light on quinoa triterpene skeletal diversity and mechanisms underlying B,C‐ring‐opened triterpene biosynthesis, opening avenues towards accessing their chemistry and biology and paving the way for quinoa trait engineering and quality improvement.

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Mimicking Halimane Synthases: Monitoring a Cascade of Cyclizations and Rearrangements from Epoxypolyprenes

Cited by 4 publications

References 81 publications

Fluorinated alcohols: powerful promoters for ring-opening reactions of epoxides with carbon nucleophiles

Fluorinated alcohols: powerful promoters for ring-opening reactions of epoxides with carbon nucleophiles

Antibacterial Natural Halimanes: Potential Source of Novel Antibiofilm Agents

Insight into neofunctionalization of 2,3‐oxidosqualene cyclases in B,C‐ring‐opened triterpene biosynthesis in quinoa

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