82-89-3

Basic information

• Product Name: PRODIGIOSIN
• Synonyms: PRODIGIOSIN;3-Methoxy-2-(5-methyl-4-pentyl-2H-pyrrol-2-ylidene)methyl-5-(1H-pyrrol-2-yl)-1H-pyrrole;4-Methoxy-5-(4-pentyl-5-methyl-2H-pyrrole-2-ylidenemethyl)-2,2'-bi[1H-pyrrole];4-Methoxy-5-[(5-methyl-4-pentyl-2H-pyrrol-2-ylidene)methyl]-2,2'-bi[1H-pyrrol];4-Methoxy-5-[(5-methyl-4-pentyl-2H-pyrrol-2-ylidene)methyl]-2,2'-bi[1H-pyrrole];Prodigiosine;4-Methoxy-5-[(5-methyl-4-pentyl-2H-pyrrol-2-ylidene)methyl], 2,2'bipyrrole;Aids010622
• CAS NO: 82-89-3
• Molecular Formula: C₂₀H₂₅N₃O
• Molecular Weight: 323.43
• Mol File: 82-89-3.mol
• Article Data: 6

Chemical Properties

• Melting Point: 151-152°
• Boiling Point: 542.4oC at 760 mmHg
• Flash Point: 281.8oC
• Appearance: /
• Density: 1.12g/cm3
• Storage Temp.: -20C
• PKA: 17.09±0.50(Predicted)
• CAS DataBase Reference: PRODIGIOSIN(CAS DataBase Reference)
• NIST Chemistry Reference: PRODIGIOSIN(82-89-3)
• EPA Substance Registry System: PRODIGIOSIN(82-89-3)

Safety Data

• Hazardous Substances Data: 82-89-3(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 82-89-3 differently. You can refer to the following data:
1. Prodigiosin is an intensely red, pyrrole pigment produced by several bacteria, most notably Serratia marcescens. Prodigiosin has a broad biological profile with activity against fungi, tumour cell lines and malaria. It was shown to be an immunosuppressant in 2007. Prodigiosin acts via caspase inhibition to induce of apoptosis in human primary cancer cells. Prodigiosin also acts as an inducer of p21WAF1/CIP1 expression via transforming growth factor-β receptor pathway, and activates NAG-1 via glycogen synthase kinase-3β.
2. Prodigiosin is an intensely red pyrrole pigment produced by several bacteria, most notably Serratia marcescens. Prodigiosin has a broad biological profile with activity against fungi, tumor cell lines and malaria. It was shown to be an immunosuppressant in 2007. Prodigiosin acts via caspase inhibition to induce of apoptosis in human primary cancer cells. Prodigiosin also acts as an inducer of p21WAF1/CIP1 expression via transforming growth factor-β receptor pathway, and activates NAG-1 via glycogen synthase kinase-3β.
3. Prodigiosin is a naturally occurring pigment which occurs as a product of Serratia marcescens. Pink colored pigment.

Definition

ChEBI: A member of the class of tripyrroles that is a red-coloured pigment with antibiotic properties produced by Serratia marcescens.

General Description

A cell-permeable tripyrrole alkaloid compound that displays immunosuppressive and anti-tumor properties irrespective of p53 status and multidrug resistance. Shown to selectively upregulate p21WAF/CIP1 and NAG-1 (nonsteroidal anti-inflammatory drug-activated gene 1) and downregulate survivin expression levels, induce mitochondria-mediated apoptosis and cell cycle arrest in tumor cells. Prevents FADD phosphorylation (IC50 = 2.0 μM in A549-FKR cells) through inhibition of FADD-kinase CK1α (IC50 ~ 6.0 μM in SW620-BGCR cells) and augments cisplatin (Cat. No. 232120)-induced apoptosis. Blocks NF-κB activation by decreasing pIκBα (by 63% at 3 μM) and IκBα levels in A549 cells, and shrinks tumor growth in A549-FKR tumor xenograft mouse model (3 mg/kg, i.p., o.d.).

Enzyme inhibitor

This red bacterial pigment (FWfree-base = 323.44 g/mol; melting point = 151- 152°C) is an antibiotic produced by Serratia marcescens (formerly Chromobacterium prodigiosum). Prodigiosin is the parent member of a class of pyrrole-containing natural products that exhibit immunosuppressive, cytotoxic, and apoptotic activity and can facilitate copper-promoted oxidative double-strand DNA cleavage through reductive activation of Cu2+. They also uncouple lysosomal vacuolar-type ATPases by promoting H+/Cl– symport activity. The solid pigment is dark red and displays a green reflex. Acidic aqueous solutions are also red, but neutral or alkaline solutions are orange-yellow. Target(s): DNA topoisomerase I; DNA topoisomerase II; FoF1 ATPase, or H+-transporting two-sector ATPase, as an uncoupler; H+/K+-ATPase, as an uncoupler; proton translocation, as an uncoupler; and Serratia marcescens nuclease.

Synthetic route

2-methyl-3-pentyl-1H-pyrrole (18320-91-7) + 4-methoxy-2,2'-bipyrrole-5-carboxaldehyde (10476-41-2) → 4-methoxy-5-[(Z)-(5-methyl-4-pentyl-2H-pyrrol-2-ylidene)methyl]-1H,1'H-2,2'-bipyrrole (82-89-3)

Conditions	Yield
hydrogenchloride In methanol at 25℃; for 12h;	59%
With hydrogenchloride 1.) methanol, 100 deg C, 5 min, 2.) methanol, 25 deg C, 30 min; Yield given. Multistep reaction;

5-(ethoxycarbonyl)-2-methyl-3-valeroylpyrrole (92198-32-8) → 4-methoxy-5-[(Z)-(5-methyl-4-pentyl-2H-pyrrol-2-ylidene)methyl]-1H,1'H-2,2'-bipyrrole (82-89-3)

Conditions	Yield
Multi-step reaction with 2 steps 2: 2.) concd. HCl / 1.) methanol, 100 deg C, 5 min, 2.) methanol, 25 deg C, 30 min View Scheme

4-methoxy-5-(methoxycarbonyl)-2,2'-bipyrrole (112373-36-1) → 4-methoxy-5-[(Z)-(5-methyl-4-pentyl-2H-pyrrol-2-ylidene)methyl]-1H,1'H-2,2'-bipyrrole (82-89-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 98 percent / hydrazine / 4 h / 25 °C 2: 97 percent / pyridine / 0.25 h / 25 °C 3: 34 percent / Na2CO3 / ethane-1,2-diol / 0.08 h / 170 °C 4: 2.) concd. HCl / 1.) methanol, 100 deg C, 5 min, 2.) methanol, 25 deg C, 30 min View Scheme
Multi-step reaction with 4 steps 1: 98 percent / NH2NH2 / 4 h / 25 °C 2: 97 percent / pyridine / 0.25 h / 25 °C 3: 34 percent / Na2CO3 / ethane-1,2-diol / 0.08 h / 170 °C 4: 59 percent / HCl / methanol / 12 h / 25 °C View Scheme

4-Methoxy-1H,1'H-[2,2']bipyrrolyl-5-carboxylic acid hydrazide (112373-37-2) → 4-methoxy-5-[(Z)-(5-methyl-4-pentyl-2H-pyrrol-2-ylidene)methyl]-1H,1'H-2,2'-bipyrrole (82-89-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 97 percent / pyridine / 0.25 h / 25 °C 2: 34 percent / Na2CO3 / ethane-1,2-diol / 0.08 h / 170 °C 3: 2.) concd. HCl / 1.) methanol, 100 deg C, 5 min, 2.) methanol, 25 deg C, 30 min View Scheme
Multi-step reaction with 3 steps 1: 97 percent / pyridine / 0.25 h / 25 °C 2: 34 percent / Na2CO3 / ethane-1,2-diol / 0.08 h / 170 °C 3: 59 percent / HCl / methanol / 12 h / 25 °C View Scheme

3-methoxy-2-(methoxycarbonyl)-1,1'-carbonyldipyrrole (112373-18-9) → 4-methoxy-5-[(Z)-(5-methyl-4-pentyl-2H-pyrrol-2-ylidene)methyl]-1H,1'H-2,2'-bipyrrole (82-89-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: 96 percent / polymer bound palladium acetate (2.79percent Pd) / acetic acid / 12 h / 80 °C 2: 88 percent / lithium methoxide / methanol / 0.08 h / 25 °C 3: 98 percent / hydrazine / 4 h / 25 °C 4: 97 percent / pyridine / 0.25 h / 25 °C 5: 34 percent / Na2CO3 / ethane-1,2-diol / 0.08 h / 170 °C 6: 2.) concd. HCl / 1.) methanol, 100 deg C, 5 min, 2.) methanol, 25 deg C, 30 min View Scheme
Multi-step reaction with 6 steps 1: 96 percent / polymer-supported Pd(II) acetate / acetic acid / 80 °C / var. reag.: Pd(OAc)2 in CH3COOH, Pd(OOCCF3)2 in CF3COOH 2: 88 percent / LiOCH3 / methanol / 0.08 h / 25 °C 3: 98 percent / NH2NH2 / 4 h / 25 °C 4: 97 percent / pyridine / 0.25 h / 25 °C 5: 34 percent / Na2CO3 / ethane-1,2-diol / 0.08 h / 170 °C 6: 59 percent / HCl / methanol / 12 h / 25 °C View Scheme

4-methoxy-5-(methoxycarbonyl)-1,1'-carbonyl-2,2'-bipyrrole (112373-19-0) → 4-methoxy-5-[(Z)-(5-methyl-4-pentyl-2H-pyrrol-2-ylidene)methyl]-1H,1'H-2,2'-bipyrrole (82-89-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: 88 percent / lithium methoxide / methanol / 0.08 h / 25 °C 2: 98 percent / hydrazine / 4 h / 25 °C 3: 97 percent / pyridine / 0.25 h / 25 °C 4: 34 percent / Na2CO3 / ethane-1,2-diol / 0.08 h / 170 °C 5: 2.) concd. HCl / 1.) methanol, 100 deg C, 5 min, 2.) methanol, 25 deg C, 30 min View Scheme
Multi-step reaction with 5 steps 1: 88 percent / LiOCH3 / methanol / 0.08 h / 25 °C 2: 98 percent / NH2NH2 / 4 h / 25 °C 3: 97 percent / pyridine / 0.25 h / 25 °C 4: 34 percent / Na2CO3 / ethane-1,2-diol / 0.08 h / 170 °C 5: 59 percent / HCl / methanol / 12 h / 25 °C View Scheme

C17H18N4O4S (112373-38-3) → 4-methoxy-5-[(Z)-(5-methyl-4-pentyl-2H-pyrrol-2-ylidene)methyl]-1H,1'H-2,2'-bipyrrole (82-89-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 34 percent / Na2CO3 / ethane-1,2-diol / 0.08 h / 170 °C 2: 2.) concd. HCl / 1.) methanol, 100 deg C, 5 min, 2.) methanol, 25 deg C, 30 min View Scheme
Multi-step reaction with 2 steps 1: 34 percent / Na2CO3 / ethane-1,2-diol / 0.08 h / 170 °C 2: 59 percent / HCl / methanol / 12 h / 25 °C View Scheme

3-methoxy-2-(methoxycarbonyl)pyrrole (112373-17-8) → 4-methoxy-5-[(Z)-(5-methyl-4-pentyl-2H-pyrrol-2-ylidene)methyl]-1H,1'H-2,2'-bipyrrole (82-89-3)

Conditions

Yield

Multi-step reaction with 7 steps 1: 1.) NaH / 1.) THF, 65 deg C, 14 h, 2.) THF, 25 deg C, 15 min 2: 96 percent / polymer-supported Pd(II) acetate / acetic acid / 80 °C / var. reag.: Pd(OAc)2 in CH3COOH, Pd(OOCCF3)2 in CF3COOH 3: 88 percent / LiOCH3 / methanol / 0.08 h / 25 °C 4: 98 percent / NH2NH2 / 4 h / 25 °C 5: 97 percent / pyridine / 0.25 h / 25 °C 6: 34 percent / Na2CO3 / ethane-1,2-diol / 0.08 h / 170 °C 7: 59 percent / HCl / methanol / 12 h / 25 °C View Scheme

4,5-diiodo-3-methoxy-2-(methoxycarbonyl)pyrrole (112373-16-7) → 4-methoxy-5-[(Z)-(5-methyl-4-pentyl-2H-pyrrol-2-ylidene)methyl]-1H,1'H-2,2'-bipyrrole (82-89-3)

Conditions

Yield

Multi-step reaction with 8 steps 1: 96 percent / H2, K2CO3 / Pd/C / methanol / 3 h / 25 °C 2: 1.) NaH / 1.) THF, 65 deg C, 14 h, 2.) THF, 25 deg C, 15 min 3: 96 percent / polymer-supported Pd(II) acetate / acetic acid / 80 °C / var. reag.: Pd(OAc)2 in CH3COOH, Pd(OOCCF3)2 in CF3COOH 4: 88 percent / LiOCH3 / methanol / 0.08 h / 25 °C 5: 98 percent / NH2NH2 / 4 h / 25 °C 6: 97 percent / pyridine / 0.25 h / 25 °C 7: 34 percent / Na2CO3 / ethane-1,2-diol / 0.08 h / 170 °C 8: 59 percent / HCl / methanol / 12 h / 25 °C View Scheme

di(n-butyl)tin oxide (818-08-6) + 4-methoxy-5-[(Z)-(5-methyl-4-pentyl-2H-pyrrol-2-ylidene)methyl]-1H,1'H-2,2'-bipyrrole (82-89-3) → C28H41N3OSn

Conditions	Yield
In methanol at 65℃;	100%

Upstream product

• 18320-91-7 2-methyl-3-pentyl-1H-pyrrole 
• 10476-41-2 4-methoxy-2,2'-bipyrrole-5-carboxaldehyde 
• 92198-32-8 ethyl 5-methyl-4-pentanoyl-1H-pyrrole-2-carboxylate 
• 112373-36-1 4-methoxy-5-(methoxycarbonyl)-2,2'-bipyrrole 
• 112373-37-2 4-Methoxy-1H,1'H-[2,2']bipyrrolyl-5-carboxylic acid hydrazide 
• 112373-18-9 3-methoxy-2-(methoxycarbonyl)-1,1'-carbonyldipyrrole 
• 112373-19-0 4-methoxy-5-(methoxycarbonyl)-1,1'-carbonyl-2,2'-bipyrrole 
• 112373-38-3 C₁₇H₁₈N₄O₄S 
• 112373-17-8 3-methoxy-2-(methoxycarbonyl)pyrrole 
• 112373-16-7 4,5-diiodo-3-methoxy-2-(methoxycarbonyl)pyrrole 

Relevant articles and documents

Pyrrole-Type compounds, compositions, and methods for treating cancer or viral diseases

The present invention relates to novel Pyrrole-Type compounds, compositions comprising Pyrrole-Type compounds, and methods useful for treating or preventing cancer or a neoplastic disorder comprising administering a composition comprising a Pyrrole-Type compound. The compounds, compositions, and methods of the invention are also useful for inhibiting the growth of a cancer cell or neoplastic cell. The present invention also relates to novel Pyrrole-Type compounds, compositions, and methods useful for treating or preventing a viral infection. The compounds, compositions, and methods of the invention are also useful for inhibiting the replication and/or infectivity of a virus.

Process for the preparation of 2,2'-bipyrrolyl-pyrromethene (prodigiosins) derivatives

The present invention is related to a process for the preparation of 5-?2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole compounds and an intermediate compound.

Total Synthesis of Prodigiosin, Prodigiosene, and Desmethoxyprodigiosin: Diels-Adler Reactions of Heterocyclic Azadienes and Development of an Effective Palladium(II)-Promoted 2,2'-Bipyrrole Coupling Procedure

The total synthesis of prodigiosin (1), a red pigment first isolated from Serratia marcescens, possessing the characteristic pyrrolylpyrromethene skeleton of a class of naturally occurring polypyrroles exhibiting antimicrobial and cytotoxic properties, is detailed.The approach is based application of an inverse electron demand Diels-Adler reaction of dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate in a 1,2,4,5-tetrazine--->1,2-diazine--->pyrrole strategy for preparation of prodigiosin pyrrole ring B and the subsequent implementation of an effective intramolecular palladium(II)-promoted 2,2'-diaryl coupling for construction of the prodigiosin 2,2'-bipyrrole AB ring system.In situ generated activated ester derivatives of pyrrole-1-carboxylic acid or the use of pyrrole-1-carboxylic acid anhydride proved suitable for the generation of mixed 1,1'-carbonyldipyrrole compounds for use in the palladium(II)-promoted mixed, 2,2'-bipyrrole coupling.Extensions of this approach to the preparation of the naturally occurring parent pyrrolylpyrromethene, prodigiosene (2a), and 2-methyl-3-pentylprodigiosene (2e, desmethoxyprodigiosin) are detailed.A comparison of the in vitro cytotoxic properties of prodigiosin (1), prodigiosene (2a), and 2-methyl-3-pentylprodigiosene (2e) are reported and reveal exceptional cytotoxic potency (3.7*10-4 μg/mL = 3.7*10-10 g/mL) for prodigiosin against 9PS (P388) mouse leukemia which may be attributed to the presence of the prodigiosin C-6 methoxy substituent.