38966-21-1

Basic information

• Product Name: APHIDICOLIN
• Synonyms: (3-ALPHA,4-ALPHA,5-ALPHA,17-ALPHA)-3,17-DIHYDROXY-4-METHYL-9,15-CYCLO-C,18-DINOR-14,15-SECOANDROSTANE-4,17-DIMETHANOL;(+)-APHIDICOLIN;APHIDICOLIN;(+)-APHIDICOLIN, NIGROSPORA ORYZAE;APC;,11a-beta,11b-beta))-;9-dimethanol,tetradecahydro-3,9-11a-methano-11ah-cyclohepta(a)naphthalene-4;dihydroxy-4,11b-dimethyl-,(3r-(3-alpha,4-alpha,4a-alpha,6a-beta,8-beta,9-beta
• CAS NO: 38966-21-1
• Molecular Formula: C20H34O4
• Molecular Weight: 338.48
• EINECS: 200-664-3
• Product Categories: Di-Terpenoids;antibiotic
• Mol File: 38966-21-1.mol

Chemical Properties

• Melting Point: 218-220°C
• Boiling Point: 394.61°C (rough estimate)
• Flash Point: 87℃
• Appearance: colorless/
• Density: 1.0057 (rough estimate)
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.4434 (estimate)
• Storage Temp.: 2-8°C
• Solubility: ethanol: soluble1mg/mL (stable at least a week at 4°C.)
• PKA: 14.24±0.70(Predicted)
• Water Solubility: Soluble in DMSO or methanol. Insoluble in water. Store solutions at -20°
• Stability: Stable for 2 years from date of purchase from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 1 month.
• Merck: 13,734
• BRN: 4689958
• CAS DataBase Reference: APHIDICOLIN(CAS DataBase Reference)
• NIST Chemistry Reference: APHIDICOLIN(38966-21-1)
• EPA Substance Registry System: APHIDICOLIN(38966-21-1)

Safety Data

• Safety Statements: 22-24
• RIDADR: NA 1993 / PGIII
• WGK Germany: 3
• RTECS: PB9185000
• F: 10-21
• Hazardous Substances Data: 38966-21-1(Hazardous Substances Data)

Usage

Uses

Used in Antiviral Applications:
APHIDICOLIN is used as an antiviral agent for its activity against herpes simplex and other viruses. It inhibits viral replication by blocking the activity of specific DNA polymerases, making it a valuable tool in the study and treatment of viral infections.
Used in Antimitotic Applications:
APHIDICOLIN is used as an antimitotic agent for its ability to block the cell cycle at the early S-phase. This property makes it useful in synchronizing cell division and as a research tool in cell differentiation studies.
Used in Apoptosis Induction:
APHIDICOLIN is used as an apoptosis inducer in leukemia cell lines and HeLaS3 cells. It potentiates apoptosis induced by arabinosyl nucleosides and has been shown to act synergistically with antitumor agents such as vincristine and doxorubicin.
Used in DNA Polymerase Inhibition:
APHIDICOLIN is used as a specific inhibitor of DNA polymerase α and δ in eukaryotic cells. It blocks the cell cycle at the early S-phase, making it a valuable tool in the study of DNA replication and cell cycle regulation.
Used in Parasitic Infections:
APHIDICOLIN is used as an active agent against Leishmania parasites, providing a potential therapeutic option for the treatment of leishmaniasis.
Used in Cancer Research:
APHIDICOLIN is used as a research tool in cancer studies due to its ability to arrest cells in the G1/S phase and increase gene amplification frequency. This property aids in understanding the mechanisms of cell cycle regulation and the development of targeted cancer therapies.
Used in Pharmaceutical Industry:
APHIDICOLIN is used as a cell synchronization agent in the pharmaceutical industry for its ability to block the cell cycle at the early S-phase, facilitating the study of cell division and differentiation.
Used in Research and Development:
APHIDICOLIN is used as a research tool in various scientific fields, including virology, cell biology, and cancer research, due to its diverse biological activities and potential applications in the development of new therapeutic strategies.

Biochem/physiol Actions

Cell permeable: yes

References

1) Syvaoja et al. (1990), DNA polymerases alpha, delta, and epsilon: three distinct enzymes from HeLa cells; Proc. Natl. Acad. Sci. USA, 87 6664 2) Urbani et al. (1995), Dissociation of nuclear and cytoplasmic cell cycle progression by drugs employed in cell synchronization; Exp. Cell Res., 219 159 3) Kuwakado et al. (1993), Aphidicolin potentiates apoptosis induced by arabinosyl nucleosides in human myeloid leukemia cell lines; Biochem. Pharmacol., 46 1909 4) Yin and Schimke (1996), Inhibition of apoptosis by overexpressing Bcl-2 enhances gene amplification by a mechanism independent of aphidicolin pretreatment; Proc. Natl. Acad. Sci. USA, 93 3394

InChI:InChI=1/C20H34O4/c1-17(11-21)15-4-3-13-9-14-10-19(13,7-8-20(14,24)12-22)18(15,2)6-5-16(17)23/h13-16,21-24H,3-12H2,1-2H3/t13-,14+,15-,16+,17-,18-,19-,20-/m0/s1

Upstream product

• 116446-56-1 <17-14C>-3α,16β,18-trihydroxyaphidicolane 
• 489-41-8 (-)-globulol 
• 88728-58-9 1,1,4,7-tetramethyldecahydro-1H-cyclopropa[e]azulen-4-ol 
• 92803-91-3 C₂₀H₃₂O₄ 
• 73697-01-5 C₂₃H₃₄O₄ 
• 92803-96-8 16β,17β-epoxyaphidicolane-3α,18-diol 
• 145656-42-4 methyl 16β-hydroxy-3-oxo-19-noraphidicolan-17-oate 
• 123252-58-4 19-noraphidicolan-3β,16β,17-triol 
• 52592-12-8 17,18-diacetoxyaphidicol-3α,16β-diol 
• 92681-41-9 17,18-diacetoxy-3α-mesyloxyaphidicol-16β-ol 
• 94789-99-8 16-epiaphidicolane-3α,16β,18-triol 
• 139559-81-2 3α,18-dihydroxyaphidicolane 
• 145656-44-6 19-norapidicolan-16β-ol 
• 52592-32-2 aphidicol-16-ene-3α,18-diol 

Downstream Products

• 52592-29-7 aphidicol-16-en 
• 52645-90-6 aphidicol-15-ene 
• 101143-85-5 aphidicolan-16β-ol 
• 85483-00-7 3-deoxyaphidicolin 
• 240409-71-6 18-phenylthioaphidicol-2-en-16β-ol 
• 240409-86-3 [17-2H]-18-phenylthioaphidicol-2-en-16β-ol 
• 38966-21-1 (+/-)-aphidicolin 
• 51103-57-2 (+)-aphidicolin 17-acetate 
• 52592-26-4 18-Phenylthio-17-noraphidicol-2-en-16-on 
• 145656-46-8 3β,17-di(p-toluenesulfonyloxy)-19-noraphidicolan-16β-ol 
• 38966-22-2 3α,18;16β,17-bisisopropylidenedioxyaphidicolane 
• 110386-56-6 3α,18-isopropylidenedioxyaphidicolane-16β,17-diol 
• 78310-60-8 16β,17-isopropylidenedioxyaphidicolane-3α,18-diol 
• 144343-34-0 3α,16β-dihydroxy-17,18-ditoluene-p-sulphonoxyaphidicolane 

Relevant articles and documents

A New End Game for Aphidicolin

A highly efficient, stereocontrolled synthesis of aphidicolin from its degradation product, 3α,18-isopropylidenedioxy-17-noraphidicolan-16-one, has been achieved.

Biosynthesis of diterpenoid aphidicolin: Isolation of intermediates from P-450 inhibitor treated mycelia of Phoma betae

Treatment of Phoma betae with P-450 inhibitors caused accumulation of biosynthetic precursors 2, 3 and 4 of aphidicolin (1). Their structures were elucidated by spectroscopic analysis and they were confirmed by chemical transformations from 1. Isotopicall

The hydroxylation at C-17 in the biosynthesis of the diterpenoid aphidicolin

The hydroxylation at C-17 in aphidicolin biosynthesis is inhibited by a 17-thiol. A metabolite hydroxylated at C-17 and retaining the cyclopropane ring was obtained from 3α,18-dihydroxy-15β,16β-methanoaphidicolane whilst aphidicolin itself was obtained from 3α,18-dihydroxyaphidicolane when these substrates were incubated with the fungus, Cephalosporium aphidicola.

THE HYDROXYLATION OF GLOBULOL AND 7-EPIGLOBULOL BY CEPHALOSPORIUM APHIDICOLA

Globulol and 7-epiglobulol were shown to be hydroxylated by Cephalosporium aphidicola on one (C-14) of the methyl groups geminal to the cyclopropane ring in 48.5 and 56percent yield, respectively.The significance of this hydroxylation adjacent to a cyclopropane ring is noted. - Key words: Cephalosporium aphidicola; globulol; 7-epiglobulol; sesquiterpenoid; microbiological hydroxylation.

Rearrangements of the C/D Ring System of the Tetracyclic Diterpenoid, Aphidicolin

The generation of a C-16 carbocation in the aphidicolane series by the hydrolysis of a 15β,16β- or a 16β,17-epoxide is shown to lead, inter alia, to skeletal rearrangement products arising from the migration of the C(12)-C(13) bond to C-16.

Oxidation of Aphidicolin and Its Conversion into 19-Noraphidicolan-16β-ol

The preparation of the 3α,18-monoacetonide of aphidicolin and its selective oxidation at C-17, is described.Catalytic oxidation of aphidicolin affords 16β-hydroxy-3-oxo-19-noraphidicolan-17-oic acid.The conversion of this into 19-noraphidicolan-16β-ol and its biotransformation by the fungus, Cephalosporium aphidicola, to a 19-noraphidicolin, is reported.

Aphidicolin Synthetic Studies: A Stereocontrolled End Game

A highly efficient, stereocontrolled synthesis of (+)-aphidicolin 1 from the well-known degradation product, acetonide 17-nor ketone 2a, has been achieved.Key steps included palladium(0)-catalysed carbonylation of the enol triflate derived from 2a and stereoselective epoxidation of the resultant α,β-unsaturated ester.Hydride reduction then furnished the C(16,17) vicinal diol moiety of 1.Similarly transformed to aphidicolin were the Corey 2,2-dimethylpropylidenedioxy synthetic intermediate 2b and the bis-tert-butyldimethylsilyl ether 2c.The latter further served as synthetic precursor to the naturally occurring derivative (+)-aphidicolin 17-acetate 26.The preparation and biological evaluation of the unnatural 16-methoxycarbonyl congeners 28 and 29 are also discussed.

Studies in Terpenoid Biosynthesis. Part 35. Biosynthetic Sequences leading to the Diterpenoid Aphidicolin in Cephalosporium aphidicola

-Labelled samples of 18-hydroxyaphidicol-16-ene, 3α,18-dihydroxyaphidicol-16-ene, 16β,17- and 16β,18-dihydroxyaphidicolane, and 3α,16β,18- and 16β,17,18-triyhdroxyaphidicolane have been prepared from aphidicolin and shown to be incorporated into aphidicolin by Cephalosporium aphidicola to the extent of 0.86, 16.4, 3.5, 20.5, 52.6, and 16,9 percent , respectively.These results suggest that although the major pathway of aphidicolin biosynthesis involves the 16β-alcohols , the 16-enes may also utilized whilst a metabolic grid relationship may exist between the variously hydroxylated 16β-alcohols.

Studies in Terpenoid Biosynthesis. Part 38. The Role of an 16β,17-Epoxyaphidicolane in the Minor Biosynthetic Pathway Leading to Aphidicolin

The hydroxylation of 2H, 17-2H3>aphidicolane-3α,16β,18-triol at C-17 in the biosynthesis of aphidicolin is shown to involve an isotope effect whilst there is no effect in the incorporation of 2H, 17-2H2>aphidicol-16-ene-3α,18-diol suggesting that the transformation of the 16-ene involves epoxidation and hydrolysis rather than hydration and hydroxylation.Feeding experiments suggest that the 16β,17-epoxyaphidicolane-3α,18-diol is involved in this transformation.