Total synthesis of (±)-paracaseolide A and initial attempts at a Lewis acid mediated dimerization of its putative biosynthetic precursor

Giera, David S.; Stark, Christian B. W.

doi:10.1039/c3ra44590a

Cited by 22 publications

(16 citation statements)

References 38 publications

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“…In the short period of time since the structure of paracaseolide A was revealed, 1 researchers in five different laboratories have reported a total synthesis of 1a involving the same final key step. 3 , 13 , 14 , 15 , 16 Namely, dimerization of the butenolide 3a ( Fig. 1 ) accompanied by dehydration has been repeatedly used to produce 1a .…”

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confidence: 99%

Diels–Alderase-free, bis-pericyclic, [4+2] dimerization in the biosynthesis of (±)-paracaseolide A

Wang

Hoye

2015

Nature Chem

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The natural product paracaseolide A is a tetracyclic dilactone containing six adjacent stereocenters. It has an unprecedented skeleton and occupies unique structural space among the >200,000 characterized secondary metabolites. Six different research groups have reported a chemical synthesis of this compound, five of which used a thermal, net Diels–Alder [4+2] cycloaddition and dehydration at 110 °C to access the target by dimerization of a simple butenolide precursor. Here we report that this dimerization proceeds under much milder conditions and with a different stereochemical outcome than previously recognized. This can be rationalized by invoking a bis-pericyclic transition state. Furthermore, we find that spontaneous epimerization, necessary to correct the configuration at one key stereocenter, is viable and that natural paracaseolide A is racemic. Together these facts point to the absence of enzymatic catalysis (i.e., Diels–Alderase activity) in the cycloaddition and strongly suggest that a non-enzyme-mediated dimerization is the actual event by which paracaseolide A is produced in Nature.

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confidence: 99%

Diels–Alderase-free, bis-pericyclic, [4+2] dimerization in the biosynthesis of (±)-paracaseolide A

Wang

Hoye

2015

Nature Chem

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“…Paracaseolide A 123 which is an inhibitor of the dual specificity phosphatase CDC25B was isolated from the stem bark of the Chinese mangrove Sonneratia paracaseolaris possesses a cage‐like tetracyclic skeleton with two long unbranched alkyl chains. A concise (5 steps) and highly yielding synthesis of 123 was achieved and reported by Stark and co‐workers in 2013 . In this total synthesis, the vital steps are the α‐iodination of a butenolide, a SMCR and a Diels‐Alder reaction.…”

Section: Coupling Of Sp2 Hybridized C–b Compoundsmentioning

confidence: 99%

“…A concise (5 steps) and highly yielding synthesis of 123 was achieved and reported by Stark and co-workers in 2013. [96] In this total synthesis, the vital steps are the α-iodination of a butenolide, a SMCR and a Diels-Alder reaction. In attempt to synthesis Paracaseolide A 123, α-halogenated butenolide 124 was reacted with vinylboronic acid or ester 125 via SMCR in the presence of Pd(dtbpf)Cl 2 in THF, promoted by CsF to obtain butenolide precursor 126.…”

Section: Hamigeran Bmentioning

confidence: 99%

“…The latter was converted to the desired target 123 in high yield (25% overal yield) in several steps including thermal Diels-Alder reaction (Scheme 23). [96] 4-Hydroxy-2-pyridone alkaloids 127-136 have gained great attention due to their biological properties such as being cytotoxic, antibacterial and antifungal which stem from their structural diversity. [97] The total synthesis achieved by starting from the commecialy available p-bromophenol 137 and readily accessisible substituted 2-pyridone 139 which are converted into known protected boronic acid 138 and bromide 140, respectively.…”

Section: Hamigeran Bmentioning

confidence: 99%

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Current Applications of Suzuki–Miyaura Coupling Reaction in The Total Synthesis of Natural Products: An update

Koshvandi

Heravi

Momeni

2018

Applied Organom Chemis

168

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Suzuki‐Miyaura Coupling Reaction (SMCR) has been extensively used in the total synthesis of natural products. We underscored these achievements in a report published in Tetrahedron up to 2012. Since then, there has been tremendous growth in this field and numerous articles have been published after 2012. In this review, we tried to go insight and highlight the current developments in the applications of SMCR as a key and strategic step (steps) in the total synthesis of biologically active natural products accomplished and reported from 2012 till date.

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“…Finally, the target 3 was synthesized after a tandem vicinal difunctinalization of a α,β-unsaturated lactone 3c to form 3d , and followed by elimination to achieve the requisite unsaturation ( Figure 12 ). In addition, researchers from other five different groups have also reported the total synthesis of 3 involving the same key step as that of Vassilikogiannakis’s protocol, namely the [4 + 2]-dimerization of 4-hydroxybutenolide ( 3a ) [ 24 , 25 , 26 , 27 , 28 ].…”

Section: The Synthesis and Modification Of Bioactive Nmpsmentioning

confidence: 99%

Synthesis and Structural Modification of Marine Natural Products

Zhang

Muehlmann

et al. 2017

Molecules

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Total synthesis of (±)-paracaseolide A and initial attempts at a Lewis acid mediated dimerization of its putative biosynthetic precursor

Cited by 22 publications

References 38 publications

Diels–Alderase-free, bis-pericyclic, [4+2] dimerization in the biosynthesis of (±)-paracaseolide A

Diels–Alderase-free, bis-pericyclic, [4+2] dimerization in the biosynthesis of (±)-paracaseolide A

Current Applications of Suzuki–Miyaura Coupling Reaction in The Total Synthesis of Natural Products: An update

Synthesis and Structural Modification of Marine Natural Products

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