24385-10-2

Basic information

• Product Name: ADRIAMYCINONE
• Synonyms: ADRIAMYCINONE;adriamycinaglycone;8-glycoloyl-7,8,9,10-tetrahydro-6,8,10,11-tetrahydroxy-1-methoxy-5,12-Naphthacenedione;Doxorubicin aglycone;Doxorubicinone;Epirubicin aglycone;5,12-Naphthacenedione, 7,8,9,10-tetrahydro-6,8,10,11-tetrahydroxy-8-(hydroxyacetyl)-1-methoxy-, (8S,10S)-;7,8,9,10-Tetrahydro-6,8,10,11-tetrahydroxy-8-(hydroxy acetyl)-1-methoxy-(8S-cis)-5,12-naphthacenedione
• CAS NO: 24385-10-2
• Molecular Formula: C₂₁H₁₈O₉
• Molecular Weight: 414.36
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Metabolites & Impurities;Metabolites & Impurities, Pharmaceuticals, Intermediates & Fine Chemicals
• Mol File: 24385-10-2.mol
• Article Data: 9

Chemical Properties

• Melting Point: 223-225°C
• Boiling Point: 726.6°C at 760 mmHg
• Flash Point: 260.4°C
• Appearance: /
• Density: 1.671g/cm³
• Vapor Pressure: 3.7E-22mmHg at 25°C
• Refractive Index: 1.737
• Storage Temp.: Amber Vial, -20°C Freezer
• Solubility: Dioxane (Slightly), DMSO (Slightly), Methanol (Slightly)
• PKA: 7.45±0.60(Predicted)
• Stability: Light Sensitive
• CAS DataBase Reference: ADRIAMYCINONE(CAS DataBase Reference)
• NIST Chemistry Reference: ADRIAMYCINONE(24385-10-2)
• EPA Substance Registry System: ADRIAMYCINONE(24385-10-2)

Safety Data

• Hazardous Substances Data: 24385-10-2(Hazardous Substances Data)

Usage

Description

ADRIAMYCINONE, also known as Doxorubicinone, is a metabolite of the anthracycline antitumor antibiotic doxorubicin. It is a red solid that exhibits various biological activities, including the inhibition of mitochondrial succinoxidase, reduction of mitochondrial inner membrane potential, and induction of cytotoxicity in cancer cells. ADRIAMYCINONE has shown potential in the field of cancer treatment due to its ability to modulate several oncological signaling pathways and induce cytotoxicity in cancer cells.

Uses

Used in Anticancer Applications:
ADRIAMYCINONE is used as an anticancer agent for its ability to inhibit mitochondrial succinoxidase, reduce mitochondrial inner membrane potential, and induce cytotoxicity in cancer cells. It has demonstrated potential in treating various types of cancer, including solid malignancies.
Used in Drug Delivery Systems:
To enhance the efficacy and bioavailability of ADRIAMYCINONE, it can be incorporated into drug delivery systems. These systems, which may include organic and metallic nanoparticles, aim to improve the delivery of ADRIAMYCINONE to cancer cells, thereby enhancing its therapeutic outcomes.

InChI:InChI=1/C21H18O9/c1-30-11-4-2-3-8-14(11)20(28)16-15(17(8)25)18(26)9-5-21(29,12(24)7-22)6-10(23)13(9)19(16)27/h2-4,10,22-23,26-27,29H,5-7H2,1H3/t10-,21-/m0/s1

Synthetic route

daunomycinone-14-bromide (29742-69-6) → adriamycinone (24385-10-2)

Conditions	Yield
With silver tetrafluoroborate In dimethyl sulfoxide at 20℃;	95%

fac-triaquatricarbonyltechnetium-99m(1+) + C43H46N4O12 → adriamycinone (24385-10-2) + C46H46N4O15(99)Tc(1+) + C25H30N4O7(99)Tc(1+)

Conditions	Yield
In water Heating;	A n/a B 90% C n/a

doxorubicin hydrochloride (25316-40-9) → adriamycinone (24385-10-2)

Conditions	Yield
With hydrogenchloride at 90℃; for 1h;	85%
With hydrogenchloride In methanol; water at 80℃; for 1.5h;	67%
With hydrogenchloride In water at 20℃; for 1 - 22h; Product distribution / selectivity;	0.21%

2NH4(1+)*ReBr3(CO)3(2-)=(NH4)2(ReBr3(CO)3) + C43H46N4O12 → adriamycinone (24385-10-2) + C46H46N4O15Re(1+) + C26H32N4O7Re(1+)

Conditions	Yield
In methanol at 60℃;	A n/a B 63% C n/a

doxorubicin (23214-92-8) → adriamycinone (24385-10-2)

Conditions	Yield
Acid hydrolysis;
With hydrogenchloride In water at 90℃;

(+)-Daunomycinone (21794-55-8) → adriamycinone (24385-10-2)

Conditions	Yield
With sodium hydroxide; bromine In aq acetone; chloroform	9.0 mg (87%)

2NH4(1+)*ReBr3(CO)3(2-)=(NH4)2(ReBr3(CO)3) + C43H46N4O12 → adriamycinone (24385-10-2) + C46H46N4O15Re(1+) + C25H30N4O7Re(1+)

Conditions	Yield
In water pH=7; pH-value; Heating;

adriamycinone (24385-10-2) + mono-4-methoxytrityl chloride (14470-28-1) → 14-O-(p-anisyldiphenylmethyl)adriamycinone (59326-04-4)

Conditions	Yield
In pyridine at 0℃; for 168h;	84%

adriamycinone (24385-10-2) → C21H16O8

Conditions	Yield
With sodium hydroxide; air 1.) H2O, room temp., 30 min; Multistep reaction;

adriamycinone (24385-10-2) → C55H83NO17Si3

Conditions	Yield
Multi-step reaction with 2 steps 1: 1H-imidazole / N,N-dimethyl-formamide 2: (triphenylphosphine)gold(I) chloride; silver(I) triflimide / dichloromethane / 0.5 h / 20 °C / Molecular sieve View Scheme

adriamycinone (24385-10-2) → 7-[2-deoxy-3,4-tetraisopropyldisiloxyl-α-L-fucopyranosyl-(1→4)-3-amino-2,3-dideoxy-α-L-fucopyranoside]-14-O-tert-butyldimethylsilyl-doxorubicinone

Conditions	Yield
Multi-step reaction with 3 steps 1: 1H-imidazole / N,N-dimethyl-formamide 2: (triphenylphosphine)gold(I) chloride; silver(I) triflimide / dichloromethane / 0.5 h / 20 °C / Molecular sieve 3: 1,3-dimethylbarbituric acid; tetrakis(triphenylphosphine) palladium(0) / dichloromethane / 0.33 h View Scheme

adriamycinone (24385-10-2) → C57H73NO19Si

Conditions	Yield
Multi-step reaction with 2 steps 1: 1H-imidazole / N,N-dimethyl-formamide 2: (triphenylphosphine)gold(I) chloride; silver(I) triflimide / dichloromethane / 0.5 h / -20 °C / Molecular sieve View Scheme

adriamycinone (24385-10-2) → C45H61NO16Si

Conditions

Yield

Multi-step reaction with 4 steps 1: 1H-imidazole / N,N-dimethyl-formamide 2: (triphenylphosphine)gold(I) chloride; silver(I) triflimide / dichloromethane / 0.5 h / -20 °C / Molecular sieve 3: 2,3-dicyano-5,6-dichloro-p-benzoquinone / dichloromethane; aq. phosphate buffer / 3.25 h / 0 - 20 °C / pH 7 4: 1,3-dimethylbarbituric acid; tetrakis(triphenylphosphine) palladium(0) / dichloromethane / 0.33 h / Inert atmosphere View Scheme

adriamycinone (24385-10-2) → 7-[2-deoxy-α-L-fucopyranosyl-(1→4)-3-amino-2,3-dideoxy-α-L-fucopyranoside]-doxorubicinone

Conditions	Yield
Multi-step reaction with 4 steps 1: 1H-imidazole / N,N-dimethyl-formamide 2: (triphenylphosphine)gold(I) chloride; silver(I) triflimide / dichloromethane / 0.5 h / 20 °C / Molecular sieve 3: 1,3-dimethylbarbituric acid; tetrakis(triphenylphosphine) palladium(0) / dichloromethane / 0.33 h 4: pyridine; pyridine hydrofluoride / 0 °C View Scheme

adriamycinone (24385-10-2) → 7-[2-deoxy-α-L-fucopyranosyl-(1→4)-3-dimethylamino-2,3-dideoxy-α-L-fucopyranoside]-doxorubicinone

Conditions

Yield

Multi-step reaction with 5 steps 1: 1H-imidazole / N,N-dimethyl-formamide 2: (triphenylphosphine)gold(I) chloride; silver(I) triflimide / dichloromethane / 0.5 h / 20 °C / Molecular sieve 3: 1,3-dimethylbarbituric acid; tetrakis(triphenylphosphine) palladium(0) / dichloromethane / 0.33 h 4: sodium tris(acetoxy)borohydride; ethanol / water / 1.5 h 5: pyridine; pyridine hydrofluoride / 0 °C View Scheme

adriamycinone (24385-10-2) → 7-[2,3-dideoxy-4-ulo-α-L-fucopyranosyl-2-deoxy-3-p-methoxybenzyl-α-L-fucopyranosyl-(1→4)-3-amino-2,3-dideoxy-α-L-fucopyranoside]-14-O-tert-butyldimethylsilyl-doxorubicinone

Conditions	Yield
Multi-step reaction with 3 steps 1: 1H-imidazole / N,N-dimethyl-formamide 2: (triphenylphosphine)gold(I) chloride; silver(I) triflimide / dichloromethane / 0.5 h / -20 °C / Molecular sieve 3: 2,3-dicyano-5,6-dichloro-p-benzoquinone / dichloromethane; aq. phosphate buffer / 3.25 h / 0 - 20 °C / pH 7 View Scheme

adriamycinone (24385-10-2) → 7-[2,3-dideoxy-4-ulo-α-L-fucopyranosyl-2-deoxy-α-L-fucopyranosyl-(1→4)-3-amino-2,3-dideoxy-α-L-fucopyranoside]-doxorubicinone

Conditions

Yield

Multi-step reaction with 5 steps 1: 1H-imidazole / N,N-dimethyl-formamide 2: (triphenylphosphine)gold(I) chloride; silver(I) triflimide / dichloromethane / 0.5 h / -20 °C / Molecular sieve 3: 2,3-dicyano-5,6-dichloro-p-benzoquinone / dichloromethane; aq. phosphate buffer / 3.25 h / 0 - 20 °C / pH 7 4: 1,3-dimethylbarbituric acid; tetrakis(triphenylphosphine) palladium(0) / dichloromethane / 0.33 h / Inert atmosphere 5: pyridine; pyridine hydrofluoride / dichloromethane / 0 °C View Scheme

adriamycinone (24385-10-2) → C53H83NO15Si3

Conditions	Yield
Multi-step reaction with 4 steps 1: 1H-imidazole / N,N-dimethyl-formamide 2: (triphenylphosphine)gold(I) chloride; silver(I) triflimide / dichloromethane / 0.5 h / 20 °C / Molecular sieve 3: 1,3-dimethylbarbituric acid; tetrakis(triphenylphosphine) palladium(0) / dichloromethane / 0.33 h 4: sodium tris(acetoxy)borohydride; ethanol / water / 1.5 h View Scheme

adriamycinone (24385-10-2) + tert-butyldimethylsilyl chloride (18162-48-6) → 14-O-tert-butyldimethylsilyl-doxorubicinone

Conditions	Yield
With 1H-imidazole In N,N-dimethyl-formamide

Upstream product

• 25316-40-9 doxorubicin hydrochloride 
• 85894-64-0 5,7-Dihydroxy-12-methoxy-5-[2-(4-methoxy-benzyloxy)-acetyl]-3a,4,5,6-tetrahydro-1,3-dioxa-benzo[de]naphthacene-8,13-dione 
• 21794-55-8 (+)-Daunomycinone 
• 23214-92-8 doxorubicin 
• 29742-69-6 daunomycinone-14-bromide 

Downstream Products

• 59326-04-4 14-O-(p-anisyldiphenylmethyl)adriamycinone 

Relevant articles and documents

Investigations into the DNA-binding mode of doxorubicinone

Cancer treatment is one of the major challenges facing the modern biomedical profession. Development of new small-molecule chemotherapeutics requires an understanding of the mechanism of action for these treatments, as well as the structure-activity relat

Doxorubicin and Aclarubicin: Shuffling Anthracycline Glycans for Improved Anticancer Agents

Anthracycline anticancer drugs doxorubicin and aclarubicin have been used in the clinic for several decades to treat various cancers. Although closely related structures, their molecular mode of action diverges, which is reflected in their biological activity profile. For a better understanding of the structure-function relationship of these drugs, we synthesized ten doxorubicin/aclarubicin hybrids varying in three distinct features: Aglycon, glycan, and amine substitution pattern. We continued to evaluate their capacity to induce DNA breaks, histone eviction, and relocated topoisomerase IIα in living cells. Furthermore, we assessed their cytotoxicity in various human tumor cell lines. Our findings underscore that histone eviction alone, rather than DNA breaks, contributes strongly to the overall cytotoxicity of anthracyclines, and structures containing N,N-dimethylamine at the reducing sugar prove that are more cytotoxic than their nonmethylated counterparts. This structural information will support further development of novel anthracycline variants with improved anticancer activity.

Stable lyophilized anthracycline glycosides

The present invention provides lyophilized and stable lyophilized anthracycline glycoside salts, in particular, the hydrochloride salt. Also, the present invention provides methods of stabilizing these anthracycline glycoside salts, and methods for producing stable lyophilized anthracycline glycoside salts, such as for example the antineoplastic compound idarubicin hydrochloride, or the compounds doxorubicin hydrochloride, and epirubicin hydrochloride.