Daunomycin. I. The Structure of Daunomycinone

Arcamone, Federico; Franceschi, Giovanni; Orezzi, P.; Cassinelli, Giuseppe; Barbieri, W.; Mondelli, R.

doi:10.1021/ja01077a059

Cited by 163 publications

(55 citation statements)

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“…They can be prepared readily [2] [5]. The A-ring of daunomycinone (4) [6] bears a hydroxy group at C (9), adjacent to the carbonyl function of the side-chain. This OH group can be introduced, in principle…”

Section: Discussionmentioning

confidence: 99%

New Dienophiles: 1‐Acetylvinyl Arenecarboxylates. Reactivity toward cyclopentadiene and exocyclic dienes

Tamariz

Vogel

1981

Helvetica Chimica Acta

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SummaryThe preparations of 1-acetylvinyl arenecarboxylates H2C=C (COCH,)OCOR with R = phenyl, p-nitrophenyl, 2,4-dinitrophenyl, u -and P-naphthyl are described (3). The Diels-A Ider reactivity of these dienophiles toward cyclopentadiene is evaluated and compared with that of methyl vinylketone, 3-trimethylsilyloxy-, 3-ethoxy-and 3-acetoxy-3-buten-2-ones. The stereoselectivity of the cycloadditions of these dienophiles with 2,3,5,6-tetramethylidene-7-oxanorbornane (1) and 5,sdimethoxy-l,4-epoxy-2,3-dimethylidene-I, 2,3,4-tetrahydroanthracene (2) is studied. In principle, the dienophiles 3 allow direct functionalization of the position C(9) of the A-ring of daunomycinone analogs by Diels-Alder additions to exocyclic dienes such as 1 and 2.

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Section: Discussionmentioning

confidence: 99%

New Dienophiles: 1‐Acetylvinyl Arenecarboxylates. Reactivity toward cyclopentadiene and exocyclic dienes

Tamariz

Vogel

1981

Helvetica Chimica Acta

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“…These features differentiating daunomycin from all known anthracyclines were considered essential for the antitumor activity, as later confirmed by structure-activity relationship studies on several other anthracyclines and derivatives. The structures of the daunomycin components were reported in August 1964 (32,33) and the total absolute configuration, shown in Figure 3, in 1968 (34). As a consequence of the RP patent application priority, a reduced production of daunomycin was programmed for 1964 to support only the ongoing clinical trials in the United States and in Italy.…”

Section: : Structure Determination Of Daunomycin and French Patenmentioning

confidence: 99%

The Roots of Modern Oncology: From Discovery of New Antitumor Anthracyclines to their Clinical Use

Cassinelli

2016

Tumori

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In May 1960, the Farmitalia CEO Dr. Bertini and the director of the Istituto Nazionale dei Tumori of Milan Prof. Bucalossi (talent scout and city's Mayor) signed a research agreement for the discovery and development up to clinical trials of new natural antitumor agents. This agreement can be considered as a pioneering and fruitful example of a translational discovery program with relevant transatlantic connections. Owing to an eclectic Streptomyces, found near Castel del Monte (Apulia), and to the skilled and motivated participants of both institutions, a new natural antitumor drug, daunomycin, was ready for clinical trials within 3 years. Patent interference by the Farmitalia French partner was overcome by the good quality of the Italian drug and by the cooperation between Prof. Di Marco, director of the Istituto Ricerche Farmitalia Research Laboratories for Microbiology and Chemotherapy, and Prof. Karnofsky, head of the Sloan-Kettering Cancer Institute of New York, leading to the first transatlantic clinical trials. The search for daunomycin's sister anthracyclines led to the discovery and development of adriamycin, one of the best drugs born in Milan. This was the second act prologue of the history of Italian antitumor discovery and clinical oncology, which started in July 1969 when Prof. Di Marco sent Prof. Bonadonna the first vials of adriamycin (doxorubicin) to be tested in clinical trials. This article reviews the Milan scene in the 1960s, a city admired and noted for the outstanding scientific achievements of its private and public institutions in drugs and industrial product discovery.

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“…The eluate contained mainly the p-anomer; 6 (CDC13): 6. 7 -0 $4-0 -Acefyl-2,3,6-trideoxy-2 -fluoro-3-tr~j7uoroacetarnido-~-Lgalactopyrat1osy1)-daunomycinone (7) and its p-anomer 8 Procedure A The syrupy glycosyl bromide (5) obtained from 100 mg (0.29 mmol) of diacetate 4 was dissolved in dry toluene (10 mL, distilled from Na), and HgBr2 (200 mg, 2 mol equiv. ), Hg(CN)2 (145 mg, 2 mol equiv.…”

Section: -0-mentioning

confidence: 99%

Synthesis and biological activity of (S)-2′-fluorodaunorubicin

Baer¹,

Siemsen²

1988

Can. J. Chem.

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Methyl 3-amino-2,3,6-trideoxy-2-fluoro-~-~-galactopyranoside was hydrolyzed to the free sugar, (S)-2-fluorodaunosamine hydrochloride, which was converted into the a , P -1,4-di-0-acetyl-N-trifluoroacetyl derivative and thence into the corresponding glycosyl bromide. The latter was condensed with daunomycinone, and the product was deprotected to give the title compound. The fluoroanthracycline displayed significant cytotoxicity against a number of tumor cell lines in vitro. Antitumor activity against L1210 murine leukemia in vivo was lower than that of the parent daunorubicin, but toxicity appeared to be reduced. HANS H. BAER et LISA SIEMSEN. Can. J. Chem. 66, 187 (1988).On a hydrolysC l'amino-3 tridtsoxy-2,3,6 fluoro-2 P-L-galactopyrannoside de mCthyle en sucre libre, le chlorhydrate de la fluoro-2-(S) daunosamine, que l'on a transform6 en dtrivt di-0-ac6tyl-a,P-l , 4 N-trifluoroacttyle et finalement en bromure de glycosyle correspondant. On a condense ce demier avec la daunomycinone et on a dtprottgk le produit pour obtenir le composC mentionnt dans le titre. La fluoroanthracycline prtsente une cytotoxicitC in vitro importante contre un certain nombre de lignes de cellules tumorales. L'activitC antitumorale in vivo contre les cellules de murine leuctmique L1210 est plus faible que celle de la daunorubicine parente; toutefois, la toxicit6 semble &tre rtduite.[Traduit par la revue]

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Daunomycin. I. The Structure of Daunomycinone

Cited by 163 publications

References 0 publications

New Dienophiles: 1‐Acetylvinyl Arenecarboxylates. Reactivity toward cyclopentadiene and exocyclic dienes

New Dienophiles: 1‐Acetylvinyl Arenecarboxylates. Reactivity toward cyclopentadiene and exocyclic dienes

The Roots of Modern Oncology: From Discovery of New Antitumor Anthracyclines to their Clinical Use

Synthesis and biological activity of (S)-2′-fluorodaunorubicin

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