Towards aflatoxins: a formal synthesis of aflatoxin B2

Eastham, Stephen A.; Ingham, Steven P.; Hallett, Michael R.; Herbert, John M.; Modi, A.N.; Morley, Timothy; Painter, James; Patel, Prakash; Quayle, Peter; Ricketts, Dean; Raftery, James

doi:10.1016/j.tet.2007.10.114

Cited by 15 publications

(4 citation statements)

References 73 publications

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“…The fact that longer reaction times resulted in identifiable amounts of the silyl ether in experiments where none had been present at shorter times suggested the possibility that the phenol 30 (or 31 ) was a metastable intermediate capable of further conversion to the silyl ether 32 (or 33 ). Indeed, we found that 30 would undergo essentially quantitative conversion to 32 via a phenolic Brook rearrangement when heated, now at 150 °C, for an extended period of time (Figure c). First-order kinetic behavior was observed, and the half-life for the conversion in 1,2-DCE was ca.…”

Section: Resultsmentioning

confidence: 99%

A Distinct Mode of Strain-Driven Cyclic Allene Reactivity: Group Migration to the Central Allene Carbon Atom

Hoye

2023

J. Am. Chem. Soc.

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Strained cyclic allenes are reactive species that can be trapped in a variety of complementary fashions that capitalize on their inherent high potential energy. 1,2,4-Cyclohexatrienes represent a subclass of allenes that, notably, can be conveniently generated by a net [4 + 2] cycloaddition within a 1,3-enyne bearing a tethered alkyne via a tetradehydro-Diels-Alder reaction. A limitation to the use of this type of thermally generated cyclic allene as a construct for the introduction of molecular complexity is their propensity to isomerize to benzenoids via a simple net 1,5-hydrogen atom migration. We have discovered that when the enyne component of the substrate is modified as an enol silyl ether (or an enol ester), migration of the silyl (or acyl) group can become the predominant event. Specifically, an appropriately electrophilic group can migrate from the O atom to the central allene carbon adjacent to the 1-siloxy(acyloxy) substituent. This process leads to highly substituted phenolic products (e.g., o-silyl phenols) following tautomerization of the intermediate cyclohexa-2,4-dienone. Experimental studies show that this novel mode of reactivity is general; DFT studies reveal the unimolecular nature of the group migration.

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Section: Resultsmentioning

confidence: 99%

A Distinct Mode of Strain-Driven Cyclic Allene Reactivity: Group Migration to the Central Allene Carbon Atom

Hoye

2023

J. Am. Chem. Soc.

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“…In 2006, Quayle’s group ( Eastham et al, 2006 ; Eastham et al, 2008 ) reported an efficient method for the formal total synthesis of aflatoxin B 2 via Wulff-Dötz reaction, as shown in Figure 10C . Starting from the C-ring compound dihydrofuran 31 , the B-ring skeleton was constructed by cobalt-mediated cyclization, and then 88 underwent a series of functional group transformations, such as ozone breaking and hydrazine to form a hydrazone, to obtain the key precursor of wulff-Dötz reaction.…”

Section: Formal Total Synthesis Of (±)-Aflatoxinsmentioning

confidence: 99%

Advances in the Total Synthesis of Aflatoxins

Yang

Wang

2021

Front. Chem.

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Aflatoxins, which are produced by Aspergillus flavus, Aspergillus nomius, and Aspergillus parasiticus, are a group of pentacyclic natural products with difuran and coumarin skeletons. They mainly include aflatoxin B1, B2, G1, G2, M1, and M2. Biologically, aflatoxins are of concern to human health as they can be present as contaminants in food products. The unique skeletons of aflatoxins and their risk to human health have led to the publication of nine remarkable total syntheses (including three asymmetric syntheses) and ten formal total syntheses (including four asymmetric formal syntheses) of aflatoxins in the past 55 years. To better understand the mechanism of the biological activity of aflatoxins and their presence in samples from the food industry, this review summarizes progress in the total synthesis of aflatoxins.

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“… Aflatoxin B 2 stands out as a prominent representative. This compound is widely known as a poisonous contaminant in improperly stored food, and many synthetic approaches to aflatoxin B 2 have been reported . Most of these syntheses rely on formation of dihydro aflatoxin D 2 , (±)- 1 , which contains the ABC ring core of aflatoxin B 2 , which is required for the formal synthesis of (±)-aflatoxin B 2 (Scheme S1).…”

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confidence: 99%

Organocatalytic Enantioselective Michael–Acetalization–Reduction–Nef Reaction for a One-Pot Entry to the Functionalized Aflatoxin System. Total Synthesis of (−)- Dihydroaflatoxin D₂ and (−)- and (+)-Microminutinin

et al. 2017

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An efficient method has been developed for the enantioselective synthesis of the aflatoxin system with multiple stereocenters via a sequence of organocatalytic Michael-acetalization-reduction-Nef reactions that proceed with high enantioselectivities (90-99% ee). The one-pot reaction sequence provides a facile entry to the aflatoxin system, including dihydroaflatoxin D, which includes a formal total synthesis of aflatoxin B. The first total synthesis of (-)- and (+)-microminutinin was also achieved via this protocol.

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Towards aflatoxins: a formal synthesis of aflatoxin B2

Cited by 15 publications

References 73 publications

A Distinct Mode of Strain-Driven Cyclic Allene Reactivity: Group Migration to the Central Allene Carbon Atom

A Distinct Mode of Strain-Driven Cyclic Allene Reactivity: Group Migration to the Central Allene Carbon Atom

Advances in the Total Synthesis of Aflatoxins

Organocatalytic Enantioselective Michael–Acetalization–Reduction–Nef Reaction for a One-Pot Entry to the Functionalized Aflatoxin System. Total Synthesis of (−)- Dihydroaflatoxin D₂ and (−)- and (+)-Microminutinin

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Towards aflatoxins: a formal synthesis of aflatoxin B2

Cited by 15 publications

References 73 publications

A Distinct Mode of Strain-Driven Cyclic Allene Reactivity: Group Migration to the Central Allene Carbon Atom

A Distinct Mode of Strain-Driven Cyclic Allene Reactivity: Group Migration to the Central Allene Carbon Atom

Advances in the Total Synthesis of Aflatoxins

Organocatalytic Enantioselective Michael–Acetalization–Reduction–Nef Reaction for a One-Pot Entry to the Functionalized Aflatoxin System. Total Synthesis of (−)- Dihydroaflatoxin D2 and (−)- and (+)-Microminutinin

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Organocatalytic Enantioselective Michael–Acetalization–Reduction–Nef Reaction for a One-Pot Entry to the Functionalized Aflatoxin System. Total Synthesis of (−)- Dihydroaflatoxin D₂ and (−)- and (+)-Microminutinin