A Novel Route to the Marasmane Skeleton via a Tandem Rearrangement−Cyclopropanation Reaction. Total Synthesis of (+)-Isovelleral

Bell, R.P.L.; Wijnberg, J. B. P. A.; Groot, Aede de

doi:10.1021/jo0015568

Cited by 28 publications

(12 citation statements)

References 25 publications

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“…Encouraged by the rapid assembly of metathesis precursor 16 , we decided to evaluate five‐ and seven‐membered ring tethers. Lactone 17 was formed by converting ketone 16 into an enol triflate, followed by deprotection and carbonylation (Scheme ) 18. However, this lactone and its reduced variants (1,4‐ and 1,2‐reductions) did not undergo ring‐closing metathesis.…”

Section: Methodsmentioning

confidence: 99%

An Efficient Substrate‐Controlled Approach Towards Hypoestoxide, a Member of a Family of Diterpenoid Natural Products with an Inside‐Out [9.3.1]Bicyclic Core

et al. 2008

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Hypoestoxide (1, Scheme 1) was isolated from the tropical shrub Hypoestes rosea, found in the Nigerian rainforests. [1] Extracts from these shrubs have been used in folk medicine for generations, to treat various skin rashes and infections. Hypoestoxide has been shown in recent studies to exhibit promising anticancer, [2] antimalarial, [3] and anti-inflammatory activity.[4] Our interest stems primarily from encouraging antiangiogenic activities, in which hypoestoxide was shown to inhibit the growth of a number of human and murine tumor cell lines in vivo. In terms of angiogenesis, hypoestoxide inhibited vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Hypoestoxide is a bicyclo[9.3.1]pentadecane diterpenoid containing a rigid "inside-outside" ring system decorated with an exocyclic enone, two epoxide moieties, and an acetate group. This rare ring system has also been described for the verticillanes, [5] of which verticillol (3, Scheme 1) [6] is the most well known. As a more oxygenated variant of verticillol, it is tempting to propose that hypoestoxide is formed from the same common cationic precursor (5) as both verticillol [7] and taxol (4), [8] which in turn originates from consecutive cyclizations of geranylgeranyl pyrophosphate. In the case of verticillol, the cation 5 is trapped with water, whereas, for taxol and hypoestoxide, it undergoes endocyclic and exocyclic eliminations, followed by oxygenations and cyclizations. As part of our efforts to evaluate the molecular mechanisms [9] of promising natural product anticancer agents we have focused our investigations on hypoestoxide and the verticillanes.Several factors needed to be considered before beginning our synthetic efforts. First, for a trans-[9.3.1]bicyclic framework, two different atropisomers are possible. Calculations (B3LYP/6-311 + G(d,p)) indicated that hypoestoxide is 4.1 kcal mol À1 more stable than the atropisomer (2). Therefore, we imagined that any such macrocyclization would preferentially form the naturally occurring atropisomer. In addition, the energy change attributed to the process of interconverting hypoestoxide and the atropisomer was estimated to be 65 kcal mol À1 . Diene 6 seemed an ideal target because it allows access to all known verticillanes, and we attempted its synthesis using a conformationally controlled ring-closing metathesis (Scheme 2). This diene provides four different options for ring-closing metathesis. Both the C5=C6 and C9=C10 bonds can originate from either a standard monosubstituted carbene or, alternatively, from a disubstituted carbene, such as 7, which can be accessed by relay metathesis.[10] Our analysis suggested that, in closing the macrocycle, it would be advantageous to bring together a more-substituted carbene with a less-hindered terminus to minimize competing dimerization pathways. We further postulated that ruthenium carbene 7 (C5=C6 disconnection) would be the better candidate for macrocyclization, since the Scheme 1. Hypoestoxide and verticillol.Scheme 2. Retr...

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Section: Methodsmentioning

confidence: 99%

An Efficient Substrate‐Controlled Approach Towards Hypoestoxide, a Member of a Family of Diterpenoid Natural Products with an Inside‐Out [9.3.1]Bicyclic Core

et al. 2008

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“…74 In 2004 Jauch's group also succeeded in generating 53 from 52 by a decarboxylation procedure. 75 Also exhibiting additional annulated five-membered rings are antrocin (54), which was first reported in 1995 by Chiang and co-workers after isolation from Antrodia cinnamomea, 76 and the closely related marasmene (55) and anhydromarasmone (56), both discovered in Marasmius oreades by the Ayer group in 1989. 77 These natural products inspired Yang and co-workers to develop an improved method to generate drimanes.…”

Section: Drimanesmentioning

confidence: 97%

“…53 In 2001 the de Groot group reported a new synthetic route to this framework. 54 A magnesium iodide induced rearrangement-cyclopropanation cascade was utilised as the key step to produce the framework; 12 was obtained in 12 steps with 10% yield starting from a known precursor.…”

Section: Syn Thesismentioning

confidence: 99%

Synthesis of Secondary Metabolites from Higher Fungi

Reck

Spiteller

2015

Synthesis

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Higher fungi are a promising source of new bioactive natural products with great structural diversity, ranging from polyketides to terpenoids and alkaloids. Many of these structures are a challenge for synthetic organic chemists who have been inspired to develop new total syntheses. Nevertheless, reviews covering syntheses of fungal natural products are lacking. One aim of this review is to close this gap and to present a selection of more recent syntheses of fungal secondary metabolites from different structural classes. Secondly, this review intends to demonstrate that there are many more motivations for the synthesis of natural products than to confirm a proposed structure or to report the first total synthesis of a new natural product. Thirdly, this review is intended to stimulate the interest of organic chemists in the synthesis of fungal natural products. 1

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“…201 A novel route to the marasmane skeleton has been utilized in the synthesis of (ϩ)-isovelleral. 202 The rearrangement of several panasinsane sesquiterpenes under acidic conditions has been studied. The panasinsane derivatives had been obtained starting from caryophyllene oxide.…”

Section: Himachalane and Longipinanementioning

confidence: 99%