Skeletal Rearrangements of Polycyclic α-Ketols

Kawamura, Moe; Kamo, Shogo; Azuma, Shuhei; Kubo, Konomi; Sasamori, Takahiro; Tokitoh, Norihiro; Kuramochi, Kouji; Tsubaki, Kazunori

doi:10.1021/acs.orglett.6b03541

Cited by 20 publications

(5 citation statements)

References 18 publications

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“…Remarkably, the 6,7-epoxide group remained unscathed in the reaction. A literature search showed that this mechanistically surprising rearrangement had already been documented in other polycyclic α-hydroxy-β-diketones, − suggesting its generality.…”

Section: Resultsmentioning

confidence: 86%

Novel Skeletal Rearrangements of the Tigliane Diterpenoid Core

Maioli,

Amin,

Chianese

et al. 2023

J. Nat. Prod.

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To investigate the role of the secondary 5-hydroxy group in the activity of the anticancer drug tigilanol tiglate ( 2b ) (Stelfonta), oxidation of this epoxytigliane diterpenoid from the Australian rainforest plant Fontainea picrosperma was attempted. Eventually, 5-dehydrotigilanol tiglate ( 3a ) proved too unstable to be characterized in terms of biological activity and, therefore, was not a suitable tool compound for bioactivity studies. On the other hand, a series of remarkable skeletal rearrangements associated with the presence of a 5-keto group were discovered during its synthesis, including a dismutative ring expansion of ring A and a mechanistically unprecedented dyotropic substituent swap around the C-4/C-10 bond. Taken together, these observations highlight the propensity of the α-hydroxy-β-diketone system to trigger complex skeletal rearrangements and pave the way to new areas of the natural products chemical space.

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Section: Resultsmentioning

confidence: 86%

Novel Skeletal Rearrangements of the Tigliane Diterpenoid Core

Maioli,

Amin,

Chianese

et al. 2023

J. Nat. Prod.

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“…This led us to speculate that 4 is the bonafide product of NzsJ that underwent a spontaneous α-ketol rearrangement reaction (Figure B). Such a rearrangement is also observed in the interconversion from the dibenzo[ b ]fluorene skeleton to a benzo[ g ]chromene in the synthetic experiments and the biogenetic interconversions between prekinamycin and isoprekinamycin (Figure S17). Density functional theory (DFT) calculations also confirmed that the structure of 4 has a higher energy than that of 5 or 6 (Table S2).…”

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confidence: 61%

Enzymatic Reconstitution and Biosynthetic Investigation of the Bacterial Carbazole Neocarazostatin A

et al. 2019

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Tricyclic carbazole is an important scaffold in many naturally occurring metabolites, as well as valuable building blocks. Here we report the reconstitution of the ring A formation of the bacterial neocarazostatin A carbazole metabolite. We provide evidence of the involvement of two unusual aromatic polyketide proteins. This finding suggests how new enzymatic activities can be recruited to specific pathways to expand biosynthetic capacities. Finally, we leveraged our bioinformatics survey to identify the untapped capacity of carbazole biosynthesis.

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“…The presence of the diazo group in intermediates 78 and 79 is noteworthy in that this functional group has not yet been demonstrated to be compatible with an α-ketol rearrangement. To test the feasibility of their hypothesis, Kawamura et al subjected 80 to basic (Cs 2 CO 3 or K 2 CO 3 ) and acidic (TsOH) conditions [ 27 ]. While TsOH led only to dehydration product 81 , the bases exclusively generated 82 as the result of an α-ketol rearrangement ( Figure 16b ).…”

Section: Reviewmentioning

confidence: 99%

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

Benz¹,

Murkin²

2021

Beilstein J. Org. Chem.

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In the presence of a suitable acid or base, α-hydroxyaldehydes, ketones, and imines can undergo isomerization that features the 1,2-shift of an alkyl or aryl group. In the process, the hydroxy group is converted to a carbonyl and the aldehyde/ketone or imine is converted to an alcohol or amine. Such α-ketol/α-iminol rearrangements are used in a wide variety of synthetic applications including asymmetric synthesis, tandem reactions, and the total synthesis and biosynthesis of natural products. This review explores the use of α-ketol rearrangements in these contexts over the past two decades.

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Skeletal Rearrangements of Polycyclic α-Ketols

Cited by 20 publications

References 18 publications

Novel Skeletal Rearrangements of the Tigliane Diterpenoid Core

Novel Skeletal Rearrangements of the Tigliane Diterpenoid Core

Enzymatic Reconstitution and Biosynthetic Investigation of the Bacterial Carbazole Neocarazostatin A

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

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