Total Synthesis of Natural and ent-Fredericamycin A

Boger, Dale L.; Hueter, Ottmar; Mbiya, K.; Zhang, Minsheng

doi:10.1021/ja00153a004

Cited by 122 publications

(57 citation statements)

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“…The broad singlet at ␦ 10.2 is assigned to the NH proton. These assignments are consistent with the isoquinolone protons observed in the natural product fredericamycin (7). The presence of a lactam ring was unambiguously supported by the 1 H-15 N HMBC experiment, in which both H-10 and H-12 showed long-range coupling to the nitrogen (Table 3).…”

Section: Sequencing Of Oxytetracycline Gene Clustersupporting

confidence: 78%

Engineered Biosynthesis of a Novel Amidated Polyketide, Using the Malonamyl-Specific Initiation Module from the Oxytetracycline Polyketide Synthase

Zhang

Ames

Tsai

et al. 2006

Appl Environ Microbiol

114

155

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Tetracyclines are aromatic polyketides biosynthesized by bacterial type II polyketide synthases (PKSs). Understanding the biochemistry of tetracycline PKSs is an important step toward the rational and combinatorial manipulation of tetracycline biosynthesis. To this end, we have sequenced the gene cluster of oxytetracycline (oxy and otc genes) PKS genes from Streptomyces rimosus. Sequence analysis revealed a total of 21 genes between the otrA and otrB resistance genes. We hypothesized that an amidotransferase, OxyD, synthesizes the malonamate starter unit that is a universal building block for tetracycline compounds. In vivo reconstitution using strain CH999 revealed that the minimal PKS and OxyD are necessary and sufficient for the biosynthesis of amidated polyketides. A novel alkaloid (WJ35, or compound 2) was synthesized as the major product when the oxy-encoded minimal PKS, the C-9 ketoreductase (OxyJ), and OxyD were coexpressed in CH999. WJ35 is an isoquinolone compound derived from an amidated decaketide backbone and cyclized with novel regioselectivity. The expression of OxyD with a heterologous minimal PKS did not afford similarly amidated polyketides, suggesting that the oxy-encoded minimal PKS possesses novel starter unit specificity.

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Section: Sequencing Of Oxytetracycline Gene Clustersupporting

confidence: 78%

Engineered Biosynthesis of a Novel Amidated Polyketide, Using the Malonamyl-Specific Initiation Module from the Oxytetracycline Polyketide Synthase

Zhang

Ames

Tsai

et al. 2006

Appl Environ Microbiol

114

155

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“…[12][13][14] for recent reviews). This reaction represents an efficient synthetic method that gives easy access to important antibiotics, [15] natural products, [16] and biologically interesting molecules. [17] It involves the formation of an ensemble between an a,b-unsaturated pentacarbonylchromium-carbene complex and an alkyne to provide phenolic (Scheme 1,…”

Section: Introductionmentioning

confidence: 99%

Dötz Benzannulation Reactions: Heteroatom and Substituent Effects in Chromium Fischer Carbene Complexes

Jiménez-Halla

Solà

2009

Chemistry A European J

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We have carried out a theoretical investigation of the Dötz reaction between acetylene and a series of chromium Fischer-type carbenes [(CO)(5)Cr=C(X)R] with different representative substituents (R=CH=CH(2), Ph) and heteroatom ligands (X=OH, NH(2), OCH(3), N(CH(3))(2)) by using density functional theory with the B3LYP functional. We have studied the Dötz and chromahexatriene mechanisms of benzannulation and also the reaction mechanism leading to cyclopentannulation. For the benzannulation, it was found that the most likely mechanism in the case of vinylcarbenes is the chromahexatriene route, whereas for phenylcarbenes, the Dötz route via a ketene intermediate is clearly the most favorable. The reactions leading to the cyclopentannulated and benzannulated products are more exothermic with vinylcarbenes than with phenylcarbenes and also more exothermic with alkoxycarbenes than with aminocarbenes. The relative stability of the cyclopentannulated products as compared with the benzannulated products increases for bulkier X substituents and on going from alkoxy- to aminocarbenes. The kinetic data concurs with the experimental product distribution found for vinylcarbenes, by which mainly benzannulated products are obtained, and dimethylaminophenylcarbenes, which lead exclusively to cyclopentannulated adducts.

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“…3c-f), and recently Boger's group reported a synthesis of optically pure natural 1 by separation of racemic protected 1 using chiral HPLC column (ref. 4), no one has so far succeeded in the asymmetric synthesis of 1, and its absolute configuration still remains unknown. Most of the reported total syntheses and the related model studies involved construction of the spiro C-or D-ring at their final stages as summarized in Scheme 1, and the lack of sufficient methods for the enantio differentiation of the highly symmetrical ABC-ring has been the handicap in their asymmetric synthesis.…”

Section: Introductionmentioning

confidence: 99%

Studies on Asymmetric Total Synthesis of Antitumor Antibiotic, Fredericamycin A.

Kita¹,

Akai²,

Fujioka³

1998

J. Syn. Org. Chem., Jpn.

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This account highlights our very recent approaches towards asymmetric total synthesis of the potent antitumor antibiotic, fredericamycin A. Due to its quite unique structure, effective methodology for its asymmetric synthesis has rarely been presented, and the absolute configuration still remains unknown. The key feature of our approaches involves the protocols for the construction of its peri-hydroxy polyaromatic skeleton bearing the chirality at the spiro carbon via (i) intramolecular [4+2]cycloaddition of silylene-protecte dihydroxystyrene derivatives, (ii) aromatic Pummerer-type reaction, and (iii) intermolecular [4+2]cycloaddition of homophthalic anhydrides. Particular attention has been given to the novel syntheses of the optically active spiro carbon center by (i) enzymatic asymmetrization of 2,2-disubstituted 1,3-diols and (ii) stereospecific rearrangement of optically active epoxy acylates.

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Total Synthesis of Natural and ent-Fredericamycin A

Cited by 122 publications

References 0 publications

Engineered Biosynthesis of a Novel Amidated Polyketide, Using the Malonamyl-Specific Initiation Module from the Oxytetracycline Polyketide Synthase

Engineered Biosynthesis of a Novel Amidated Polyketide, Using the Malonamyl-Specific Initiation Module from the Oxytetracycline Polyketide Synthase

Dötz Benzannulation Reactions: Heteroatom and Substituent Effects in Chromium Fischer Carbene Complexes

Studies on Asymmetric Total Synthesis of Antitumor Antibiotic, Fredericamycin A.

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