(7S,9S)-9-acetyl-6,7,9,11-tetrahydroxy-7,8,9,10-tetrahydrotetracene-5,12-dione

Base Information

• Chemical Name: (7S,9S)-9-acetyl-6,7,9,11-tetrahydroxy-7,8,9,10-tetrahydrotetracene-5,12-dione
• CAS No.: 60660-75-5
• Molecular Formula: C20H16 O7
• Molecular Weight: 368.343
• DSSTox Substance ID: DTXSID20976091
• Nikkaji Number: J408.669D
• Wikidata: Q82960861
• ChEMBL ID: CHEMBL3544591
• Mol file: 60660-75-5.mol

Synonyms:4-demethoxydaunomycinone

Chemical Property of (7S,9S)-9-acetyl-6,7,9,11-tetrahydroxy-7,8,9,10-tetrahydrotetracene-5,12-dione

Chemical Property:

• Vapor Pressure: 1.63E-16mmHg at 25°C
• Boiling Point: 625.6°C at 760 mmHg
• Flash Point: 346.2°C
• PSA: 132.13000
• Density: 1.626g/cm³
• LogP: 1.17290
• Storage Temp.: Sealed in dry,Room Temperature
• XLogP3: 1.7
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 1
• Exact Mass: 368.08960285
• Heavy Atom Count: 27
• Complexity: 675

Purity/Quality:

98%,99%, ^*data from raw suppliers

(7S,9S)-9-Acetyl-6,7,9,11-tetrahydroxy-7,8,9,10-tetrahydro-5,12-naphthacenedione ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(=O)C1(CC(C2=C(C1)C(=C3C(=C2O)C(=O)C4=CC=CC=C4C3=O)O)O)O
• Isomeric SMILES: CC(=O)[C@]1(C[C@@H](C2=C(C1)C(=C3C(=C2O)C(=O)C4=CC=CC=C4C3=O)O)O)O
• General Description: (7S,9S)-9-Acetyl-7,8,9,10-tetrahydro-6,7,9,11-tetrahydroxy-5,12-naphthacenedione, also known as 4-demethoxydaunomycinone or idarubicinone, is a key intermediate in the synthesis of anthracycline antibiotics such as idarubicin. It features a tetracyclic naphthacenedione core with hydroxyl groups at positions 6, 7, 9, and 11, and an acetyl group at position 9. (7S,9S)9-ACETYL-7,8,9,10-TETRAHYDRO-6,7,9,11-TETRAHYDROXY-5,12-NAPHTACENEDIONE is synthesized through functionalization of the A-ring, including the introduction of a cis-7,9-diol moiety, and resolution of racemic precursors. Its derivatives, such as idarubicinone-7-β-D-glucuronide, are explored for improved pharmacological properties, leveraging glycosylation strategies to enhance drug efficacy. (7S,9S)9-ACETYL-7,8,9,10-TETRAHYDRO-6,7,9,11-TETRAHYDROXY-5,12-NAPHTACENEDIONE’s stereochemistry and functional groups are critical for its role as a precursor in antineoplastic drug development.

Technology Process of (7S,9S)-9-acetyl-6,7,9,11-tetrahydroxy-7,8,9,10-tetrahydrotetracene-5,12-dione

There total 4 articles about (7S,9S)-9-acetyl-6,7,9,11-tetrahydroxy-7,8,9,10-tetrahydrotetracene-5,12-dione which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 45.0%

4-demethoxy-9-deoxydaunomycinone-6,7-acetonide (134665-41-1) → (+/-)-9-acetyl-6,7,9,11-tetrahydroxy-7,8,9,10-tetrahydronaphthacen-5,12-dione (60660-75-5,60733-78-0,63268-39-3,65877-42-1,70005-90-2,70005-91-3,74606-73-8,84773-46-6,58924-49-5) + 8-Acetyl-6,11-dihydroxy-naphthacene-5,12-dione (84499-12-7)

Guidance literature:

With potassium tert-butylate; oxygen; triethyl phosphite; In N,N-dimethyl-formamide; tert-butyl alcohol; at -20 ℃; for 0.416667h;

Reference yield: 9.0%

Acetic acid 2,4,12-triacetoxy-2-acetyl-6,11-dioxo-1,2,3,4,6,11-hexahydro-naphthacen-5-yl ester (84499-10-5,84499-11-6) → (+/-)-9-acetyl-6,7,9,11-tetrahydroxy-7,8,9,10-tetrahydronaphthacen-5,12-dione (60660-75-5,60733-78-0,63268-39-3,65877-42-1,70005-90-2,70005-91-3,74606-73-8,84773-46-6,58924-49-5) + 9-acetyl-5,7,9,11-tetrahydroxy-7,8,9,10-tetrahydronaphthacene-5,12-dione (65877-42-1) + 8-Acetyl-6,11-dihydroxy-naphthacene-5,12-dione (84499-12-7)

Guidance literature:

With hydrogenchloride; sodium hydrogencarbonate; 1.) MeOH-H₂O, reflux, 3 d, 2.) MeOH-THF, RT, 15 min;

DOI:10.1021/ja00344a031

Reference yield: 0.59%

idarubicin hydrochloride (57852-57-0,60660-73-3) → (7S,9S)-idarubicinone (60660-75-5) + 8-Acetyl-6,11-dihydroxy-naphthacene-5,12-dione (84499-12-7)

Guidance literature:

With ammonia; In water; at 4 - 20 ℃; for 25 - 149h; pH=6.56 - 6.69; Product distribution / selectivity;

upstream raw materials:

idarubicin hydrochloride

4-demethoxy-9-deoxydaunomycinone-6,7-acetonide

9-acetoxy-9-acetyl-7-bromo-7,8,9,10-tetrahydro-6,11-diacetoxy-5,12-naphthacenedione

Acetic acid 2,4,12-triacetoxy-2-acetyl-6,11-dioxo-1,2,3,4,6,11-hexahydro-naphthacen-5-yl ester

Downstream raw materials:

3-acetyl-3,5,12-trihydroxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-1-naphthacenyl 2-(acetyloxy)-2-phenyl ethanoate

3-acetyl-3,5,12-trihydroxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-1-naphthacenyl 2-(acetyloxy)-2-phenylethanoate

(7S,9S)-9-acetyl-7-<(3'-amino-2',3',6'-trideoxy-α-L-arabinohexopyranosyl)oxy>-7,8,9,10-tetrahydro-6,9,11-trihydroxy-5,12-naphthacenedione

idarubicin hydrochloride

Refernces

An improved route to 4 demethoxydaunomycinone. A-ring functionalization and resolution studies of tetracyclic precursors

10.1021/ja00344a031

The research focuses on the development of an improved synthetic route to 4-demethoxydaunomycinone (24), a significant intermediate in the synthesis of the antineoplastic drug 4-demethoxydaunomycin. The study explores the functionalization of the A-ring of tetracyclic precursors, particularly the introduction of the cis-7,9-diol functionality and the resolution of racemic 4-demethoxy-7-deoxydaunomycinone (16) into its enantiomers using Enders' hydrazine reagent. Key chemicals involved in the research include 4-demethoxy-7,9-dideoxydaunomycinone (4), its dimethyl ether (5), various reagents such as perchloric acid, acetic anhydride, m-chloroperbenzoic acid, and sodium hydroxide for the functionalization steps, and Enders' hydrazine reagent for the resolution process. The research also involves the synthesis and characterization of several intermediate compounds, such as enol acetate 7, epoxy acetate 12, hydroxy ketones 16 and 19, and the 7-bromo derivatives 21 and 22, which are crucial for achieving the desired functionalization and resolution. The study provides detailed procedures and conditions for the synthesis of these compounds, contributing to the development of a practical and efficient route for the preparation of 4-demethoxydaunomycinone in multigram quantities.

Facile total syntheses of idarubicinone-7-β-D-glucuronide: Convenient preparations of AB-ring synthon using some carboxylic acid derivatives

10.1081/SCC-120030758

The study presents a facile total synthesis of idarubicinone-7-β-D-glucuronide, an anthracycline antibiotic analog, using a series of carboxylic acid derivatives as key intermediates. The researchers employed polyphosphoric acid (PPA) and AlCl3 as catalysts to cyclize dimethoxybenzene with various carboxylic acid derivatives, yielding naphthalenones, which were further transformed into (+)-idarubicinone 3b. Esterification with (S)-(+)-O-acetylmandelic acid and subsequent separation and deprotection steps led to the isolation of (+)-3b and (2)-3b. These compounds were then glycosylated with acetobromo-α-D-glucuronic acid methyl ester, using ZnBr2 as a catalyst, to produce two kinds of idarubicinone-7-β-D-glucuronide (20 and 21). The synthesized compounds were intended to enhance drug efficacy, potentially improving the pharmacological profile of idarubicinone by attaching glucuronic acid moieties. The study also detailed the synthetic method for an AB-ring synthon necessary for the synthesis of the aglycone and provided a comprehensive analysis of the synthesized compounds using various analytical techniques.