23668-11-3

Basic information

• Product Name: Pactamycin
• Synonyms: A 80856F30;NSC52947;Pactamycin;2-Hydroxy-6-methylbenzoic acid [(1S)-5α-[(3-acetylphenyl)amino]-4β-amino-3β-[[(dimethylamino)carbonyl]amino]-1β,2α-dihydroxy-3-[(S)-1-hydroxyethyl]-2-methylcyclopentyl]methyl ester;2-Hydroxy-6-methylbenzoic acid [[(1S)-5α-(3-acetylphenylamino)-4β-amino-3β-(3,3-dimethylureido)-1β,2α-dihydroxy-3-[(S)-1-hydroxyethyl]-2-methylcyclopentan-1α-yl]methyl] ester;2-Hydroxy-6-methylbenzoic acid [(1S,2R,3R,4S,5S)-5-[(3-acetylphenyl)amino]-4-amino-3-[[(dimethylamino)carbonyl]amino]-1,2-dihydroxy-3-[(1S)-1-hydroxyethyl]-2-methylcyclopentyl]methyl ester;PNU-0015800;U-15800
• CAS NO: 23668-11-3
• Molecular Formula: C₂₈H₃₈N₄O₈
• Molecular Weight: 558.628
• Mol File: 23668-11-3.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 626.7°C (rough estimate)
• Flash Point: 428.1°C
• Appearance: white to tan/
• Density: 1.2608 (rough estimate)
• Vapor Pressure: 6.66E-26mmHg at 25°C
• Refractive Index: 1.5500 (estimate)
• Storage Temp.: 2-8°C
• Solubility: DMSO: ≥12mg/mL
• CAS DataBase Reference: Pactamycin(CAS DataBase Reference)
• NIST Chemistry Reference: Pactamycin(23668-11-3)
• EPA Substance Registry System: Pactamycin(23668-11-3)

Safety Data

• Hazard Codes: T+
• Statements: 28-36/37/38
• Safety Statements: 26-28-36/37-45
• RIDADR: UN 2811 6.1 / PGII
• Hazardous Substances Data: 23668-11-3(Hazardous Substances Data)

Usage

Safety Profile

Poison by ingestion, intravenous, and intraperitoneal routes. Mutation data reported. When heated to decomposition it emits toxic fumes of NOx.

Enzyme inhibitor

This universal translation inhibitor (FW = 558.63 g/mol; CAS 23668-11-3; soluble in ethanol and benzene; Abbreviation: Pct) from Streptomyces pactum, previously known as NSC 52947 and named systematically as benzoic acid, 2-hydroxy-6-methyl-[(1S,2R,3R,4S,5S)-5-[(3-acetylphenyl) amino]-4-amino-3-[[(dimethylamino)carbonyl]amino]-1,2-dihydroxy-3- [(1S)-1-hydroxyethyl]-2-methylcyclopentyl]methyl ester, inhibits protein synthesis and exhibits antitumor activity. Because the optical rotation of dissolved pactamycin changes upon standing, some as-yet undefined chemical rearrangement must take place. Solutions should be freshly prepared. Primary Mode of Inhibitory Action: Pct restricts structural transitions in ribosomal RNA, preventing the ribosome blocks the binding of initiator tRNA to the initiator complex, preventing formation of the 80S ribosomal complex and arresting protein biosynthesis immediately after the initial dipeptide is formed. Binding Interactions: Pct binds in a single site on the 30S ribosome subunit in the upper part of the platform, very close to the cleft in the subunit that is responsible for binding of the three tRNA molecules. It interacts primarily with residues at the tips of the stem loops H23b and H24a in the central domain of 16S RNA, where it folds up to mimic an RNA dinucleotide. The interaction between N6 of A694 and Pct is crucial for binding of the drug since this is the only interaction with that particular base. N-methylation of this residue causes resistance, most likely from distortions of the local structure

InChI:InChI=1/C28H38N4O8/c1-15-9-7-12-20(35)21(15)24(36)40-14-27(39)23(30-19-11-8-10-18(13-19)16(2)33)22(29)28(17(3)34,26(27,4)38)31-25(37)32(5)6/h7-13,17,22-23,30,34-35,38-39H,14,29H2,1-6H3,(H,31,37)/t17-,22-,23-,26-,27+,28-/m0/s1

Upstream product

• 123-54-6 acetylacetone 
• 1449329-24-1 benzyl ((1S,2R,3R,4S,5S)-5-((3-acetylphenyl)amino)-2-(3,3-dimethylureido)-3,4-dihydroxy-2-((S)-1-hydroxyethyl)-4-(hydroxymethyl)-3-methylcyclopentyl)carbamate 
• 438187-09-8 2-hydroxy-6-methyl-benzoic acid cyanomethyl ester 
• 29397-21-5 Diacetyldiazomethan 
• 99-03-6 1-(3-aminophenyl)ethanone 
• 1449329-20-7 benzyl ((1R,2R,3R,5R)-3-((S)-1-((tert-butyldimethylsilyl)oxy)ethyl)-3-(3,3-dimethylureido)-5-(hydroxymethyl)-4-oxo-6-oxabicyclo[3.1.0]hexan-2-yl)carbamate 
• 1449329-18-3 C₂₅H₄₁N₃O₇Si 
• 1449329-12-7 3-(2,4-dioxopentan-3-yl)-1,1-dimethylurea 
• 1449329-25-2 ((1S,2R,3R,4S,5S)-5-((3-acetylphenyl)amino)-4-(((benzyloxy)carbonyl)amino)-3-(3,3-dimethylureido)-1,2-dihydroxy-3-((S)-1-hydroxyethyl)-2-methylcyclopentyl)methyl 2-hydroxy-6-methylbenzoate 
• 1449329-23-0 benzyl ((1S,2R,3R,4S,5S)-5-((3-acetylphenyl)amino)-2-((S)-1-((tert-butyldimethylsilyl)oxy)ethyl)-4-(((tert-butyldiphenylsilyl)oxy)methyl)-2-(3,3 dimethylureido)-3,4-dihydroxy-3-methylcyclopentyl)carbamate 
• 1449329-22-9 benzyl ((1R,2R,3R,4R,5R)-3-((S)-1-((tert-butyldimethylsilyl)oxy)ethyl)-5-(((tert-butyldiphenylsilyl)oxy)methyl)-3-(3,3-dimethylureido)-4-hydroxy-4-methyl-6-oxabicyclo[3.1.0]hexan-2-yl)carbamate 
• 1449329-21-8 benzyl ((1R,2R,3R,5R)-3-((S)-1-((tert-butyldimethylsilyl)oxy)ethyl)-5-(((tert-butyldiphenylsilyl)oxy)methyl)-3-(3,3-dimethylureido)-4-oxo-6-oxabicyclo[3.1.0] hexan2-yl)carbamate 

Downstream Products

• 69313-72-0 Pactamycin-Aceton-Addukt 
• 23754-55-4 pactamycate 

Relevant articles and documents

Preparation and biological evaluation of synthetic and polymer-encapsulated congeners of the antitumor agent pactamycin: Insight into functional group effects and biological activity

The synthesis and biological analysis of a number of novel congeners of the aminocyclopentitol pactamycin is described. Specific attention was paid to the preparation of derivatives at crucial synthetic branch points of the parent structure, and biological assays revealed a number of insights into the source of pactamycin's biological activity. Additionally, the encapsulation of pactamycin and select derivatives into the PRINT

Asymmetric synthesis of the aminocyclitol pactamycin, a universal translocation inhibitor

An asymmetric total synthesis of the aminocyclopentitol pactamycin is described. The title compound is delivered in 15 steps from 2,4-pentanedione. Critical to this approach was the exploitation of a complex symmetry-breaking reduction strategy to assemble the C1, C2, and C7 relative stereochemistry within the first four steps of the synthesis. Multiple iterations of this reduction strategy are described, and a thorough analysis of stereochemical outcomes is detailed. In the final case, an asymmetric Mannich reaction was developed to install a protected amine directly at the C2 position. Symmetry-breaking reduction of this material gave way to a remarkable series of stereochemical outcomes leading to the title compound without recourse to nonstrategic downstream manipulations. This synthesis is immediately accommodating to the preparation of structural analogs.

Total synthesis of pactamycin and pactamycate: A detailed account

This article describes synthetic studies that culminated in the first total synthesis of pactamycin and pactamycate and, in parallel, the two known congeners, de-6-MSA-pactamycin and de-6-MSA-pactamycate, lacking the 6-methylsalicylyl moiety. Starting with l-threonine as a chiron, a series of stereocontrolled condensations led to a key cyclopentenone harboring a spirocyclic oxazoline. A series of systematic functionalizations led initially to the incorrect cyclopentanone epoxide, which was "inverted" under solvolytic conditions. Installation of the remaining groups and manipulation of the oxazoline eventually led to pactamycin, pactamycate, and their desalicylyl analogues.