35596-02-2

Basic information

• Product Name: 2,3,4,7-tetra-O-acetylnarciclasine
• Synonyms: 2,3,4,7-tetra-O-acetylnarciclasine
• CAS NO: 35596-02-2
• Molecular Weight: 475.409
• Mol File: 35596-02-2.mol

Chemical Properties

• CAS DataBase Reference: 2,3,4,7-tetra-O-acetylnarciclasine(CAS DataBase Reference)
• NIST Chemistry Reference: 2,3,4,7-tetra-O-acetylnarciclasine(35596-02-2)
• EPA Substance Registry System: 2,3,4,7-tetra-O-acetylnarciclasine(35596-02-2)

Safety Data

• Hazardous Substances Data: 35596-02-2(Hazardous Substances Data)

Upstream product

• 108-24-7 acetic anhydride 
• 29477-83-6 narciclasine 

Relevant articles and documents

Human cytochrome P450 liability studies of trans-dihydronarciclasine: A readily available, potent, and selective cancer cell growth inhibitor

The cytochrome P45O activities of the naturally occurring Amaryllidaceae alkaloid narciclasine (3), isolated from Narcissus pseudonarcissus, and synthetic derivative trans-dihydronarciclasine (5) are reported. While narciclasine was found to possess potent inhibitory activity to human CYP3A4, its dihydro analogue was inactive. This study revealed that the C1-C10b double bond is required for inhibition of this crucial metabolizing enzyme. Compound 5 also demonstrated no inhibition of the related human cytochromes CYP19 and CYP1A1. This study elevates the status of trans-dihydronarciclasine (5) as a highly privileged, readily available molecule, with potent and selective anticancer activity.

Antineoplastic agents. 454. Synthesis of the strong cancer cell growth inhibitors trans-dihydronarciclasine and 7-deoxy-trans-dihydronarciclasine

To further pursue the antineoplastic leads offered by our isolation of trans-dihydronarciclasine (1a) and 7-deoxy-transdihydronarciclasine (1c) from two medicinal plant species of the Amaryllidaceae family, a practical palladium-catalyzed hydrogenation procedure was developed for the synthesis of these isocarbostyrils from narciclasine (2a) and 7-deoxynarciclasine (2c).

Structure-activity relationship analysis of novel derivatives of narciclasine (an Amaryllidaceae isocarbostyril derivative) as potential anticancer agents

Narciclasine (1) is a plant growth regulator that has been previously demonstrated to be proapoptotic to cancer cells at high concentrations (≥ 1 μM). Data generated in the present study show that narciclasine displays potent antitumor effects in apoptosis-resistant as well as in apoptosis-sensitive cancer cells by impairing the organization of the actin cytoskeleton in cancer cells at concentrations that are not cytotoxic (IC 50 values of 30-90 nM). The current study further revealed that any chemical modification to the narciclasine backbone generally led to compounds of variable stability, weaker activity, or even the complete loss of antiproliferative effects in vitro. However, one hemisynthetic derivative of narciclasine, compound 7k, demonstrated by both the intravenous and oral routes higher in vivo antitumor activity in human orthotopic glioma models in mice when compared to narciclasine at nontoxic doses. Narciclasine and compound 7k may therefore be of potential use to combat brain tumors.

SYNTHESIS OF SODIUM NARCISTATIN AND RELATED COMPOUNDS

The present invention involves use of the compounds narciclasine (2a) and 7-deoxy-narciclasine (2c), which are obtained via isolation from the medicinal plant species Narcissus (Amaryllidaceae), as precursors in a novel synthesis method in which each of these compounds are selectively hydrogenated to produce trans-dihydronarciclasine (1a) and 7-deoxy-trans-dihydronarciclasine (1c). Also described herein is a novel synthesis method for producing sodium narcistatin (11) from narciclasine (2a). Further described herein are certain novel 3,4-cyclic phosphate prodrugs, including sodium-7-deoxynarcistatin (8), sodium-7-deoxy-transdihydronarcistatin (9), and sodium transdihydronarcistatin (10).

Synthesis of 10b(R)-hydroxypancratistatin, 10b(S)-hydroxy-1-epipancratistatin, 10b(S)-hydroxy-1,2-diepipancratistatin and related isocarbostyrils

Narciclasine (2) was transformed by a series of reactions where Sharpless asymmetric hydroxylations served as the stereochemical controlling step to 10b(R)-hydroxypancratistatin (3), 10b(S)-hydroxy-1-epipancratistatin (13) and 10b(S)-hydroxy-1,2-diepipancratistatin (16). Synthesis of 10b(S)-hydroxy-1,2-diepipancratistatin (16) proceeded from α-triol (11) via cyclic sulfate (14) and inversion of C-2 with cesium benzoate followed by saponification and treatment with a catalytic amount of acid. Compared to pancratistatin (1), these structural modifications led to decreased cancer cell growth inhibition against a minipanel of human cancer cell lines. Narciclasine (2) inhibited the pathogenic yeast Cryptococcus neoformans, and modifications (4, 14 and 15) inhibited growth of the pathogenic bacterium Neisseria gonorrhoeae.