A novel synthesis of (+)-4-demethoxydaunomycinone

Cabri, Walter; Bernardinis, S. De; Francalanci, F.; Penco, Sergio

doi:10.1039/p19900000428

Cited by 26 publications

(5 citation statements)

References 5 publications

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“…The mutated anthracycline-producing strains can also result in novel compounds, some of which have found their way into clinical use, including doxorubicin, obtained from a mutant of daunorubicin-producing S. peucetius . The synthetic modification of a microbially produced anthracycline substrate has also resulted in successful developments, of which menogaril derived from nogalamycin 1 and idarubicin derived from daunorubicin are examples. However, an emerging technology for novel anthracycline production is the combination of the biosynthetic pathways from different Streptomyces strains by transfer of those genes responsible for metabolite synthesis from one organism into another, producing or blocked, host strain.…”

Section: Introductionmentioning

confidence: 99%

Hybrid Anthracyclines from a Genetically EngineeredStreptomycesgalilaeusMutant

et al. 2000

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The genetic engineering of antibiotic-producing Streptomyces strains is an approach that is emerging and ready to become established as a successful methodology in developing analogues of the original, pharmaceutically important, natural products obtained from the organisms. The current report highlights this succes by demonstrating the high-level production of novel anthracyclines. The biosynthetic pathways of the nogalamycin-producing Streptomyces nogalater and the aclacinomycin-producing S. galilaeus were combined by transferring the genes of S. nogalater polyketide synthetase into a nonproducing S. galilaeus mutant. The resulting anthracycline antibiotics that were produced possessed structural features characteristic of compounds from both of the undoctored Streptomycesstrains.

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Section: Introductionmentioning

confidence: 99%

Hybrid Anthracyclines from a Genetically EngineeredStreptomycesgalilaeusMutant

et al. 2000

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“…2 The mutation of existing strains can lead to compounds with improved curative properties, of which doxorubicin is an example. 3 Furthermore, numerous semisynthetic products have been produced amongst which the most interesting are idarubicin 4 and menogaril. 5 The laborious and random nature of these approaches however demanded the development of a new, more efficient methodology.…”

Section: Introductionmentioning

confidence: 99%

Hybrid compounds derived from the combination of anthracycline and actinorhodin biosynthetic pathways

Kunnari¹,

Kantola²,

Ylihonko³

et al. 1999

J. Chem. Soc., Perkin Trans. 2

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A new approach in the field of polyketide biosynthetic engineering, the combination of the biosynthetic routes of two different sources, is introduced. Streptomyces nogalater genes expressed in S. lividans TK24 yield the hybrid strain TK24/pSY15. Structural analysis of the products isolated from cultivation of the hybrid strain revealed the ability of the hybrid to produce novel compounds. Instead of accumulating characteristic products (e.g. actinorhodin) of the host S. lividans TK24, or intermediate compounds expected to be generated by the plasmid pSY15 (e.g. nogalamycin precursor), the hybrid strain produces novel compounds reflecting the enzymatic activity of both the host and the expressed plasmid. This implies that genes from two different types of aromatic polyketide biosynthesis are working together. The method described in this work complements earlier targeted biosyntheses.

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“…Idarubicin is marketed worldwide under the trademark Zavedos. The preparation of 44 is also carried out by semisynthesis from daunomycinone, easily obtained upon acid hydrolysis of biosynthetic daunorubicin 124. This process involves demethylation of the starting daunomycinone 46 a to carminomycinone 46 b , conversion of the latter to the 13‐ethylidene ketal 47 a , and then to the 4‐O‐triflate 47 b .…”

Section: Anthracyclinesmentioning

confidence: 99%

“…The preparation of 44 is also carried out by semisynthesis from daunomycinone, easily obtained upon acid hydrolysis of biosynthetic daunorubicin. [124] This process involves demethylation of the starting daunomycinone 46 a to carminomycinone 46 b, conversion of the latter to the 13-ethylidene ketal 47 a, and then to the 4-O-triflate 47 b. The subsequent step, which leads, after deprotection, to 4-deoxy derivative 44 (Scheme 7), is based on the deoxygenation reaction of phenols discovered by Cacchi.…”

Section: Anthracyclinesmentioning

confidence: 99%

Fifty Years of Chemical Research at Farmitalia

Arcamone¹

2009

Chemistry A European J

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This review contains a brief description of the chemistry developed in Farmitalia and, after 1978, Farmitalia-Carlo Erba Research Laboratories, during the second half of the last century. It gives an overview of work that represents a significant part of the chemistry carried out in Italy during this period in the field of medicinal and natural product chemistry. This is particularly true when we consider in addition to the work done intramurally in the said laboratories, the work done by academic scientists in the frame of the various extramural collaborations. Only a fraction of the chemical research actually carried out is reported here as time and space dictated a selection. Subjects typically associated with Farmitalia and which gave rise to important scientific or therapeutic outcomes are given preference in this review.

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A novel synthesis of (+)-4-demethoxydaunomycinone

Cited by 26 publications

References 5 publications

Hybrid Anthracyclines from a Genetically EngineeredStreptomycesgalilaeusMutant

Hybrid Anthracyclines from a Genetically EngineeredStreptomycesgalilaeusMutant

Hybrid compounds derived from the combination of anthracycline and actinorhodin biosynthetic pathways

Fifty Years of Chemical Research at Farmitalia

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