Total Synthesis of FR901483

Ousmer, Malika; Braun, Norbert A.; Ciufolini, Marco A.

doi:10.1021/ol015526i

Cited by 65 publications

(21 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The tetramate derivative (R)-9 was synthesized by condensation of methyl (E)-4-chloro-3-methoxy-2-butenoate (10) [25] with the chiral auxiliary (R)-11 [24,26] in the presence of triethylamine with acetonitrile as the solvent. After refluxing the reaction mixture for 6 h, tetramate (R)-9 was obtained in 61 % yield with an ee value of 98.8 % (Scheme 1).…”

Section: Resultsmentioning

confidence: 99%

A Flexible Asymmetric Approach to Methyl 5‐Alkyltetramates and Its Application in the Synthesis of Cytotoxic Marine Natural Product Belamide A

Lan

Wang

et al. 2010

Chemistry A European J

View full text Add to dashboard Cite

By using a methyl tetramate derivative (R)- or (S)-9 as a novel chiral building block, a direct, flexible, and highly enantioselective approach to methyl (R)- or (S)-5-alkyltetramates (2) is disclosed. Among the synthesized methyl 5-alkyltetramates 2, methyl 5-methyltetramate (2 a) is found in cytotoxic mirabimide E (4) and dysideapyrrolidone (5), and methyl 5-benzyltetramate (2 g) is a substructure in the potent antineoplastic dolastatin 15 (3). On the basis of this method, the first asymmetric synthesis of the antimitotic tetrapeptide belamide A (7) has been achieved in seven steps from (S)-9, with an overall yield of 23.8 %. Not only have the structure and absolute configuration of (+)-belamide A (7) been confirmed, but also the solvent used for recording the (13) C NMR spectrum, the (13) C NMR spectrum data correlation, and optical rotation data of natural belamide A (7) have been revised.

show abstract

Section: Resultsmentioning

confidence: 99%

A Flexible Asymmetric Approach to Methyl 5‐Alkyltetramates and Its Application in the Synthesis of Cytotoxic Marine Natural Product Belamide A

Lan

Wang

et al. 2010

Chemistry A European J

View full text Add to dashboard Cite

show abstract

“…[29,30] Interestingly, this quinone has two electrophilic carbon atoms available for nucleophilic 1,4-addition. Addition to the C atom at the C(1) position would furnish the five-membered ring spiro compound III, a reaction that has been postulated for the biosynthesis of some natural products such as FR901483 [31,32] or TAN1251 A.…”

Section: Resultsmentioning

confidence: 99%

Mechanistic Studies on the Tyrosinase‐Catalyzed Formation of the Anachelin Chromophore

Gademann

2005

ChemBioChem

View full text Add to dashboard Cite

The complex secondary metabolite anachelin, isolated from the freshwater cyanobacterium Anabaena cylindrica, is believed to act as siderophore, facilitating iron uptake. Its structure is characterized by a fascinating blend of polyketide, peptide, and alkaloid fragments. In particular, the tetrahydroquinolinium-derived chromophore is unique among natural products, and its biosynthesis is unknown. We propose a hypothesis for the biogenesis of the anachelin chromophore starting from a C-terminally bound L-Tyr residue. It is proposed that this amino acid is reductively aminated, methylated, and hydroxylated. Oxidation of this catechol diamine substrate by a tyrosinase would lead to an o-quinone, which would react by intramolecular aza-annulation and tautomerization to give the anachelin chromophore. In order to evaluate this hypothesis, a model substrate related to the proposed biogenetic precursor was prepared. It was shown that the enzyme tyrosinase is able to transform this substrate into an anachelin chromophore derivative, which corroborates the biogenetic hypothesis. In order to gain further insight into the mechanism of this transformation, we performed spectrophotometric reaction monitoring, allowing the formation of the expected product to be observed. In addition, a rise in absorption at around 250 nm might be due to the presence of a spiro five-membered ring intermediate resulting from an alternative 1,4-addition to the o-quinone. Lastly, we were able to show that the action of tyrosinase on this substrate follows Michaelis-Menten kinetics (k(cat)=123 s(-1) and K(m)=8.66 mM). Interestingly, the catalytic efficiency is decreased only by a factor of 30 relative to the natural substrate L-DOPA.

show abstract

“…As highlighted in the previous section, many oxidative dearomatizations involve the introduction of soft heteroatomic nucleophiles. [39] Despite a few sparse examples, CÀC bond formation during oxidative dearomatization is of significant interest in complex natural product synthesis. [40] Recently, Kita and co-workers have developed catalytic processes for iodoarene-catalyzed C À C bond formations of phenols.…”

Section: Oxidative and Alkylative Dearomatization Of Phenols Withmentioning

confidence: 99%

Dearomatization Strategies in the Synthesis of Complex Natural Products

Roche¹,

Porco²

2011

Angew Chem Int Ed

1,191

397

View full text Add to dashboard Cite

Evolution in the field of the total synthesis of natural products has led to exciting developments over the last decade. Numerous chemo-selective and enantioselective methodologies have emerged from total syntheses, resulting in efficient access to many important natural product targets. This Review highlights recent developments concerning dearomatization, a powerful strategy for the total synthesis of architecturally complex natural products wherein planar, aromatic scaffolds are converted to three-dimensional molecular architectures.

show abstract

Total Synthesis of FR901483

Cited by 65 publications

References 18 publications

A Flexible Asymmetric Approach to Methyl 5‐Alkyltetramates and Its Application in the Synthesis of Cytotoxic Marine Natural Product Belamide A

A Flexible Asymmetric Approach to Methyl 5‐Alkyltetramates and Its Application in the Synthesis of Cytotoxic Marine Natural Product Belamide A

Mechanistic Studies on the Tyrosinase‐Catalyzed Formation of the Anachelin Chromophore

Dearomatization Strategies in the Synthesis of Complex Natural Products

Contact Info

Product

Resources

About