Pneumocandin B0
[CAS# 135575-42-7]

Identification

• Classification: API >> Other chemicals
• Name: Pneumocandin B0
• Synonyms: (10R,12S)-N-[(3S,6S,9S,11R,15S,18S,20R,21R,24S,25S)-3-[(1R)-3-amino-1-hydroxy-3-oxopropyl]-6-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-11,20,21,25-tetrahydroxy-15-[(1R)-1-hydroxyethyl]-2,5,8,14,17,23-hexaoxo-1,4,7,13,16,22-hexazatricyclo[22.3.0.09,13]heptacosan-18-yl]-10,12-dimethyltetradecanamide
• Molecular Formula: C₅₀H₈₀N₈O₁₇
• Molecular Weight: 1065.21
• CAS Registry Number: 135575-42-7
• EC Number: 629-746-0
• SMILES: CC[C@H](C)C[C@H](C)CCCCCCCCC(=O)N[C@H]1C[C@H]([C@H](NC(=O)[C@@H]2[C@H](CCN2C(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@@H](NC1=O)[C@@H](C)O)O)[C@@H]([C@H](C4=CC=C(C=C4)O)O)O)[C@@H](CC(=O)N)O)O)O)O

Properties

• Density: 1.4±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.630, Calc.^*
• Boiling Point: 1442.9±65.0 °C (760 mmHg), Calc.^*
• Flash Point: 826.5±34.3 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS05;GHS07;GHS08 Danger
• Risk Statements: H315-H317-H318-H334-H335-H400
• Safety Statements: P233-P260-P261-P264-P264+P265-P271-P272-P273-P280-P284-P302+P352-P304+P340-P305+P354+P338-P317-P319-P321-P332+P317-P333+P317-P342+P316-P362+P364-P391-P403-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Skin irritation	Skin Irrit.	2	H315
Serious eye damage	Eye Dam.	1	H318
Skin sensitization	Skin Sens.	1	H317
Respiratory sensitization	Resp. Sens.	1	H334
Specific target organ toxicity - single exposure	STOT SE	3	H335
Reproductive toxicity	Repr.	2	H361

Discovery and Applications

Pneumocandin B0, a potent antifungal agent, was discovered in the 1970s by researchers at Merck & Co., Inc. The discovery originated from soil samples collected from a diverse range of environments, including forest floors and agricultural fields. Through a rigorous screening process, scientists identified a strain of fungus, Glarea lozoyensis, as the producer of pneumocandin B0. This natural compound exhibited remarkable antifungal activity against a broad spectrum of fungal pathogens, particularly those resistant to existing antifungal agents.

Pneumocandin B0 and its derivatives, collectively known as echinocandins, are used for the treatment of invasive fungal infections, particularly those caused by Candida species and Aspergillus species. These infections pose significant risks to immunocompromised patients, such as those undergoing chemotherapy or organ transplantation. Pneumocandin B0 inhibits the synthesis of ß-(1,3)-D-glucan, a key component of the fungal cell wall, leading to cell lysis and fungal death. Pneumocandin B0 is indicated for the treatment of candidemia and invasive candidiasis, serious fungal infections associated with high morbidity and mortality rates. Candidemia occurs when Candida species enter the bloodstream, leading to systemic infection, while invasive candidiasis involves the invasion of Candida into deep tissues and organs. Pneumocandin B0's efficacy in these life-threatening infections has made it a first-line treatment option in many clinical settings. Pneumocandin B0 may be used prophylactically in high-risk patients to prevent invasive fungal infections. This includes individuals undergoing hematopoietic stem cell transplantation, solid organ transplantation, or those with prolonged neutropenia. Pneumocandin B0 is generally well-tolerated, with a favorable safety profile compared to other antifungal agents. It has minimal nephrotoxicity and hepatotoxicity, making it suitable for use in patients with renal or hepatic impairment.

References

1992. Pneumocandins from Zalerion arboricola. I. Discovery and isolation. The Journal of Antibiotics, 45(12).
DOI: 10.7164/antibiotics.45.1853

2021. Glyap1 regulates pneumocandin B0 synthesis by controlling the intracellular redox balance in Glarea lozoyensis. Applied Microbiology and Biotechnology, 105(18).
DOI: 10.1007/s00253-021-11522-5

2024. Exploration of the pneumocandin biosynthetic gene cluster based on efficient CRISPR/Cas9 gene editing strategy in Glarea lozoyensis. International Journal of Biological Macromolecules, 279.
DOI: 10.1016/j.ijbiomac.2024.135220