Enantioselective total synthesis of medermycin (lactoquinomycin)

Tatsuta, Kuniaki; Ozeki, Hidekazu; Yamaguchi, M.; Tanaka, Masashi; Okui, Toshiharu

doi:10.1016/s0040-4039(00)97881-x

Cited by 83 publications

(39 citation statements)

References 11 publications

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“…The residue, after evaporation of the solvent, was subjected to chromatography on silica gel (Wako-gel C200) with chloroform/methanol (15 : 1) to give medermycin (5 mg). The purified compound gave NMR data (available as supplementary data with the online version of this paper at http://mic.sgmjournals.org) consistent with the published values for natural medermycin/lactoquinomycin A (Okabe et al, 1985;Tatsuta et al, 1990;Williamson et al, 2002).…”

Section: Methodssupporting

confidence: 78%

“…K73 (Takano et al, 1976). Its structure was shown (Tatsuta et al, 1990) to be identical with lactoquinomycin A, independently characterized as an anticancer compound from Streptomyces tanashiensis Okabe et al, 1985). Medermycin featured in the first production of hybrid antibiotics by genetic engineering (Hopwood et al, 1985), where a medermycin producer, Streptomyces sp.…”

Section: Introductionmentioning

confidence: 99%

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Cloning, sequencing and heterologous expression of the medermycin biosynthetic gene cluster of Streptomyces sp. AM-7161: towards comparative analysis of the benzoisochromanequinone gene clusters

et al. 2003

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Medermycin is a Streptomyces aromatic C-glycoside antibiotic classified in the benzoisochromanequinones (BIQs), which presents several interesting biosynthetic problems concerning polyketide synthase (PKS), post-PKS tailoring and deoxysugar pathways. The biosynthetic gene cluster for medermycin (the med cluster) was cloned from Streptomyces sp. AM-7161. Completeness of the clone was proved by the heterologous expression of a cosmid carrying the entire med cluster in Streptomyces coelicolor CH999 to produce medermycin. The DNA sequence of the cosmid (36 202 bp) revealed 34 complete ORFs, with an incomplete ORF at either end. Functional assignment of the deduced products was made for PKS and biosynthetically related enzymes, tailoring steps including strereochemical control, oxidation, angolosamine pathway, C-glycosylation, and regulation. The med cluster was estimated to be about 30 kb long, covering 29 ORFs. An unusual characteristic of the cluster is the disconnected organization of the minimal PKS genes: med-ORF23 encoding the acyl carrier protein is 20 kb apart from med-ORF1 and med-ORF2 for the two ketosynthase components. Secondly, the six genes (med-ORF14, 15, 16, 17, 18 and 20) for the biosynthesis of the deoxysugar, angolosamine, are all contiguous. Finally, the finding of a glycosyltransferase gene, med-ORF8, suggests a possible involvement of conventional C-glycosylation in medermycin biosynthesis. Comparison among the three complete BIQ gene clusters – med and those for actinorhodin (act) and granaticin (gra) – revealed some common genes whose deduced functions are unavailable from database searches (the ‘unknowns’). An example is med-ORF5, a homologue of actVI-ORF3 and gra-ORF18, which was highlighted by a recent proteomic analysis of S. coelicolor A3(2).

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Section: Methodssupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Cloning, sequencing and heterologous expression of the medermycin biosynthetic gene cluster of Streptomyces sp. AM-7161: towards comparative analysis of the benzoisochromanequinone gene clusters

et al. 2003

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“…We have already reported the first total syntheses of related antibiotics such as nanaomycin D (1) [8], kalafungin (2) [9,10], and BE-52534B (3) [11] (Fig. 1), and developed synthetic strategy for the stereoselective construction of densely-functionalized pyranonaphthoquinones from carbohydrates [12][13][14][15][16][17][18][19][20][21][22][23][24]. During synthetic studies on nanaomycin D (1) and kalafungin (2), a new methodology to enable to synthesize both enantiomers from one enantiomeric carbohydrate had been developed in our laboratory, meaning ''enantiodivergent synthesis'' [12,13,[25][26][27][28][29][30].…”

Section: The Total Syntheses Of Nanaomycin D and Kalafunginmentioning

confidence: 99%

Total syntheses of bioactive natural products from carbohydrates

Tatsuta

Hosokawa

2006

Science and Technology of Advanced Materials

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Total syntheses of bioactive natural products recently accomplished in our laboratories are described. They are classified by structures of target molecules and are focused on our original approach to their own structures. The target molecules include nanaomycin, kalafungin, BE-54238B, tetracycline, rosmarinecine, thienamycin, luminacines C 1 and C 2 , tetrodecamycin, cochleamycin A, and tubelactomicin A, which have been synthesized as optically pure form from carbohydrates.

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“…2 Recently our attention has been directed towards the synthesis of some of the more complex pyranonaphthoquinone antibiotics which contain C-glycoside moieties as typified by medermycin 1 3 and mederrhodin 2. 4 To date only one lengthy synthesis of medermycin 1 has been reported 5 in which the pyranonaphthalene skeleton was assembled by addition of a Cglycosyl-sulfonylphthalide to an enone. Given the significant biological activity exhibited by Cglycosylpyranonaphthoquinone antibiotics such as medermycin 1, we embarked on a flexible synthetic programme that would provide access to a range of C-glycosidic pyranonaphthoquinones for biological evaluation.…”

Section: Introductionmentioning

confidence: 99%

“…Repeating the reaction on the same scale but with dry acetonitrile (2 mL) as the solvent gave exclusively the β-C-glycoside 22 (49 mg, 97%) which was recrystallized from ethanol to give colourless needles, mp 127. 5 …”

mentioning

confidence: 99%

C-Glycosylation of naphthols using glycosyl donors

Brenstrum¹,

Brimble²

2001

Arkivoc

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Attempts to effect direct C-glycosylation of naphthols 6, 7, and 8 using glucosyl donors 9 and 10 were unsuccessful. O-Glycosides 11, 12 and 15 were obtained under Mitsunobu conditions, however, these failed to undergo rearrangement to the C-glycosides 13, 14 and 16, respectively. Successful Cglycosylation of naphthols 7 and 8 was realized using the more reactive 2-deoxyglucosyl acetate donor 18 with trimethylsilyl triflate and silver perchlorate as the Lewis acid promoters. Use of acetonitrile as solvent formed the C-glycosides 20 and 22 in preference to the corresponding O-glycosides 19 and 21, respectively.

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Enantioselective total synthesis of medermycin (lactoquinomycin)

Cited by 83 publications

References 11 publications

Cloning, sequencing and heterologous expression of the medermycin biosynthetic gene cluster of Streptomyces sp. AM-7161: towards comparative analysis of the benzoisochromanequinone gene clusters

Cloning, sequencing and heterologous expression of the medermycin biosynthetic gene cluster of Streptomyces sp. AM-7161: towards comparative analysis of the benzoisochromanequinone gene clusters

Total syntheses of bioactive natural products from carbohydrates

C-Glycosylation of naphthols using glycosyl donors

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