40041-97-2

Upstream product

• 558-18-9 2,2-dimethoxypropane 
• 29477-83-6 narciclasine 
• 77-76-9 2,2-dimethoxy-propane 
• 235757-42-3 methyl 6-<(3aS,4R,7R,7aR)-7-hydroxy-2,2-dimethyl-4-<(phenylmethoxy)amino>-6-phenylthio-2,3,4,7,3a,7a-hexahydro-1,3-dioxainden-5-yl>-4-methoxy-2H-benzo1,3-dioxolene-5-carboxylate 
• 67-64-1 acetone 

Downstream Products

• 29477-83-6 narciclasine 
• 28233-43-4 4,7-dihydroxy-[1,3]dioxolo[4,5-j]phenanthridin-6(5H)-one 
• 40042-02-2 (3aS)-6-hydroxy-2,2-dimethyl-(3ar,12ac)-3a,4,11,12a-tetrahydro-bis[1,3]dioxolo[4,5-c;4',5'-j]phenanthridine-5,12-dione 
• 1019642-59-1 C₂₄H₂₁NO₈ 
• 1019643-17-4 C₃₁H₂₅NO₉ 
• 412911-17-2 2-benzoyl-10b(S)-1,2-diepipancratistatin 

Relevant academic research and scientific papers

Isolation, Synthesis, and Semisynthesis of Amaryllidaceae Constituents from Narcissus and Galanthus sp.: De Novo Total Synthesis of 2-epi-Narciclasine

An efficient protocol for the isolation of narciclasine from common Amaryllidaceae bulbs, separation from haemanthamine, and the occurrence of a trace alkaloid, 2-epi-narciclasine, are reported. Attempts to convert natural narciclasine to its C-2 epimer by Mitsunobu inversion or oxidation/reduction sequences were compromised by rearrangement and aromatization processes, through which a synthesis of the alkaloid narciprimine was achieved. The methylation of the 7-hydroxy group of natural narciclasine followed by protection of the 3,4-diol function and oxidation/reduction sequence provided the target C-2 epimer. A de novo chemoenzymatic synthesis of 2-epi-narciclasine from m-dibromobenzene is also described. Haemanthamine and narciprimine were readily detected in the crude extracts of Narcissus and Galanthus bulbs containing narciclasine, and the occurrence of 2-epi-narciclasine as a trace natural product in Galanthus sp. is reported for the first time.

Narciclasine derivative, and preparation and application thereof in preparation of antitumor drugs

The invention provides a narciclasine derivative represented by the following structural formula I, wherein R1 is alkyl, cycloalkyl, benzyl or substituted benzyl, R2 is alkyl, cycloalkyl, benzyl or substituted benzyl, and n is an integer from 1 to 10. The narciclasine derivative is subjected to a tumor cell toxicity killing effect test, and results prove that the narciclasine derivative has strong toxicity killing effects on lung gland tumor cells, intestinal tumor cells, breast tumor cells, liver tumor cells, prostate tumor cells, melanoma tumor cells, endometrial tumor cells and neuroglia tumor cells, so the narciclasine derivative can be used for preparation of antitumor drugs. The invention provides a preparation method of the narciclasine derivative. The narciclasine derivative has a novel side-chain structure, shows excellent inhibitory activity on a variety of tumor cell strains, has drug efficacy better than that of narciclasine, allows toxic and side effects of the compound to be improved, provides new drugs for treatment of malignant tumors, and is of great clinical application value.

NOVEL ANTI-CANCER ISOCARBOSTYRIL ALKALOID CONJUGATES

The present application is directed to covalent conjugates between an isocarbostyril alkaloid and a lipophilic biomolecule, to pharmaceutical compositions comprising the conjugates and to therapeutic uses thereof, in particular for treating cancer.

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 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.

Antineoplastic agents. 450. Synthesis of (+)-pancratistatin from (+)-narciclasine as relay

(+)-Narciclasine (2) available in quantity from certain Amaryllidaceae species or by total synthesis was employed as a precursor for a 10-step synthetic conversion (3.6% overall yield) to natural (+)-pancratistatin (1a). The key procedures involved epoxidation of natural (+)-narciclasine (2) to epoxide 6, reduction to diol 8, and formation of cyclic sulfate 12 and its ring opening with cesium benzoate followed by saponification of the benzoate to afford (+)-pancratistatin (1a).

Total syntheses of (-)-lycoricidine, (+)-lycoricidine, and (+)- narciclasine via 6-exo cyclizations of substituted vinyl radicals with oxime ethers

The development of an approach to the total synthesis of the title alkaloids is described. The approach utilizes as the key strategic element a stereoselective 6-exo radical cyclization of a vinyl radical to an O- benzyloxime radical acceptor group. The vinyl radical was itself generated by regioselective addition of phenylthiyl radical to a disubstituted alkyne. The regiochemical issues of such additions, which result in different outcomes with tri-n-butylstannyl radicals and phenylthiyl radicals, are discussed. The first such synthesis described, that of (-)-lycoricidine, proceeded in 14 steps and 11% overall yield from 10 and served to develop the radical chemistry required. A second-generation synthesis, this time of the natural (+) enantiomer, was developed using insights gleaned from the first study and proved much more efficient, providing the target alkaloid in nine steps and 44% overall yield. This approach was then employed in the more demanding case of (+)-narciclasine. Several problems arising due to the more electron rich aromatic moiety present in this structure are described. The synthesis developed to deal with these aspects afforded (+)-narciclasine in 12 steps and 26% overall yield.