29477-83-6

Usage

Uses

Used in Pharmaceutical Industry:
Narciclasine is used as an antiproliferative and pro-apoptotic inducer for its potential anticancer properties. It has been shown to induce apoptosis-mediated cytotoxicity in human cancer cells in vitro, specifically targeting cancer cells while sparing normal fibroblasts. This selective action makes it a promising candidate for cancer treatment.
Used in Chemical Synthesis:
Narciclasine is used as a valuable intermediate in the synthetic conversion of (+)-pancratistatin, a natural product with potential therapeutic applications. Its unique structure and properties make it a useful starting point for the development of new pharmaceutical compounds.
Used in Plant Biology Research:
As a plant growth inhibitor, narciclasine is used in research to study the regulation of the Rho/Rho kinase/LIM kinase/cofilin signaling pathway. It has been shown to increase GTPase RhoA activity and induce actin stress fiber formation in a RhoA-dependent manner, providing insights into the molecular mechanisms of plant growth and development.
Used in Analytical Chemistry:
Narciclasine's distinct optical activity and fluorescence properties make it a useful compound for analytical purposes. Its interaction with FeCl3, resulting in a violet color, can be utilized for identification and quantification in various analytical techniques.

References

Ceriotti., Nature, 213,595 (1967)Piozzi et al., Tetrahedron, 24, 1119 (1968)Revised structure: Mondon, Krohn., Tetrahedron Lett., 2123 (1970)Savona, Piozzi, Marino., Chern. Cornrnun., 1006 (1970)Absolute configuration: Fuganti, Mazza.,J. Chern. Soc., Chern. Cornrnun., 239 (1972)Crystal structure: Immirzi, Fuganti., J. Chern. Soc., Chern. Cornrnun., 240 (1972)Stereochemistry: Mondon, Krohn., Tetrahedron Lett., 2085 (1972)

InChI:InChI=1/C14H13NO7/c16-6-1-5-4-2-7-13(22-3-21-7)11(18)8(4)14(20)15-9(5)12(19)10(6)17/h1-2,6,9-10,12,16-19H,3H2,(H,15,20)/t6-,9+,10+,12-/m0/s1

Upstream product

• 40041-97-2 (2S,5aS,2aR,5bR)-2,8-dihydroxy-4,4-dimethyl-2,6,2a,5a,5b-pentahydro-10H-1,3-dioxolano<4,5-c>1,3-dioxoleno<4,5-j>phenanthridin-7-one 
• 28245-31-0 (2S,3R,4S,4aR)-2,3,4-trihydroxy-7-methoxy-3,4,4a,5-tetrahydro-[1,3]dioxolo[4,5-j]phenanthridin-6(2H)-one 
• 474526-63-1 (2S,3S,4R,4aR)-5-(t-butoxycarbonyl)-2-((t-butyldimethylsilyl)oxy)-7-(o-carbamoyloxypiperonyl)-3,4-(isopropylidenedioxy)-8,9-(methylenedioxy)-2,3,4,4a-tetrahydrophenanthridone 
• 474526-55-1 (1S,2S,3S,6R)-3-((t-butyldimethylsilyl)oxy)-1,2-O-isopropylidene-6-(N-(p-nitrobenzenesulfonyl)amino)cyclohexene-1,2-diol 
• 7797-83-3 2H-benzo[d]1,3-dioxolane-4-carbaldehyde 
• 228242-67-9 7-aminocarbomethoxy-2,2-dimethyl-6-(7-methoxybenzo[d][1,3]dioxol-5-yl)-(3aS,7R,7aS)-4,7-dihydro[d][1,3]dioxol-4-one 
• 55623-92-2 (3aS)-12c-hydroxy-6-methoxy-2,2-dimethyl-(3ar,3bt,12ac)-3b,4,12,12a-tetrahydro-3aH-bis[1,3]dioxolo[4,5-c;4',5'-j]phenanthridin-5-one 
• 228242-68-0 methyl ((3aS,4R,7R,7aR)-7-hydroxy-7'-methoxy-2,2-dimethyl-3a,4,7,7a-tetrahydro-[5,5'-bibenzo[d][1,3]dioxol]-4-yl)carbamate 
• 228242-62-4 1,8-dibromo-11-carbomethoxy-4,4-dimethyl-(1R,2S,6S,7S)-3,5,10,11-trioxaazatricyclo[5.2.2.0^2,6]-8-undecene 
• 460731-66-2 4,6-dibromo-2,2-dimethyl-(3aS,7aS)-benzo[d](1,3)-dioxole 
• 228242-61-3 3,5-dibromo-(1S,2S)-3,5-cyclohexadiene-1,2-diol 
• 29477-83-6 narciclasine 

Downstream Products

• 28245-31-0 (2S,3R,4S,4aR)-2,3,4-trihydroxy-7-methoxy-3,4,4a,5-tetrahydro-[1,3]dioxolo[4,5-j]phenanthridin-6(2H)-one 
• 55623-84-2 (4aR)-2t,4c-dihydroxy-3c,7-dimethoxy-(4ar)-3,4,4a,5-tetrahydro-2H-[1,3]dioxolo[4,5-j]phenanthridin-6-one 
• 55623-96-6 (3aS)-6,12c-dihydroxy-(3ar,3bt,12ac)-3b,4,12,12a-tetrahydro-3aH-spiro[bis[1,3]dioxolo[4,5-c;4',5'-j]phenanthridine-2,1'-cyclohexan]-5-one 
• 28526-38-7 acetic acid 2,4-diacetoxy-7-hydroxy-6-oxo-2,3,4,4a,5,6-hexahydro[1,3]dioxolo[4,5-j]phenanthridin-3-yl ester 
• 35596-02-2 2,3,4,7-tetra-O-acetylnarciclasine 
• 40042-06-6 2,3,4,7-tetraacetoxy-cis-dihydronarciclasine 
• 40042-07-7 2,3,4,7-tetraacetoxy-trans-dihydronarciclasine 
• 1019642-48-8 sodium sulfate mono-(2,3,7-trihydroxy-6-oxo-2,3,4,4a,5,6-hexahydro-[1,3]dioxolo[4,5-j]phenanthridin-4-yl) ester 
• 40041-97-2 (2S,5aS,2aR,5bR)-2,8-dihydroxy-4,4-dimethyl-2,6,2a,5a,5b-pentahydro-10H-1,3-dioxolano<4,5-c>1,3-dioxoleno<4,5-j>phenanthridin-7-one 
• 29477-83-6 (2R,3R,4S,4aR)-2,3,4,7-tetrahydroxy-3,4,4a,5-tetrahydro-[1,3]dioxolo[4,5-j]phenanthridin-6(2H)-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 

Relevant academic research and scientific papers

ISOCARBOSTYRIL ALKALOIDS AND FUNCTIONALIZATION THEREOF

Enantioselective total syntheses of the anticancer isocarbostyril alkaloids (+)-7-deoxypancratistatin, (+)-pancratistatin, (+)-lycoricidine, and (+)-narciclasine are described. Our strategy for accessing this unique class of natural products is based on the development of a Ni-catalyzed dearomative trans-1,2-carboamination of benzene. The effectiveness of this dearomatization approach is notable, as only two additional olefin functionalizations are needed to construct the fully decorated aminocyclitol cores of these alkaloids. Installation of the lactam ring has been achieved through several pathways and a direct interconversion between natural products was established via a late-stage C-7 cupration. Using this synthetic blueprint, we were able to produce natural products on a gram scale and provide tailored analogs with improved activity, solubility, and metabolic stability.

Enantioselective Synthesis of Isocarbostyril Alkaloids and Analogs Using Catalytic Dearomative Functionalization of Benzene

Enantioselective total syntheses of the anticancer isocarbostyril alkaloids (+)-7-deoxypancratistatin, (+)-pancratistatin, (+)-lycoricidine, and (+)-narciclasine are described. Our strategy for accessing this unique class of natural products is based on the development of a Ni-catalyzed dearomative trans-1,2-carboamination of benzene. The effectiveness of this dearomatization approach is notable, as only two additional olefin functionalizations are needed to construct the fully decorated aminocyclitol cores of these alkaloids. Installation of the lactam ring has been achieved through several pathways and a direct interconversion between natural products was established via a late-stage C-7 cupration. Using this synthetic blueprint, we were able to produce natural products on a gram scale and provide tailored analogs with improved activity, solubility, and metabolic stability.

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.

A short synthesis of (+)-narciclasine via a strategy derived from stereocontrolled epoxide formation and SnCl4-catalyzed arene-epoxide coupling

A facile construction of the typical framework of narcissus alkaloids has been realized by virtue of the development of a practical route involving stereocontrolled epoxide formation and SnCl4-catalyzed arene-epoxide coupling. To achieve this goal, it proved to be necessary to devise a strategy that would enable chemical transformations to install an epoxy moiety in a congested environment. The successful preparation of a hindered epoxide from O-isopropylidene-protected 4-aminocyclohexenol required three steps consisting principally of controlled bromohydration and base-promoted closure and N-alkylation. It was found that a catalytic amount of SnCl4 not only maintained the catalytic cycle but also effected clean arylation to form a fused BC ring system. Several tactics that ultimately proved to be unsatisfactory are also discussed in an effort to set important boundary limits on arene-epoxide coupling. The requisite enantiopure 4-aminocyclohexenol was available via an asymmetric cycloaddition of diene to camphor-based chloronitroso. The total synthesis of (+)-narciclasine was realized in nine steps with an overall yield of 19%.

Total synthesis and biological evaluation of Amaryllidaceae alkaloids: narciclasine, ent-7-deoxypancratistatin, regioisomer of 7-deoxypancratistatin, 10b-epi-deoxypancratistatin, and truncated derivatives.

Biocatalytic approaches have yielded efficient total syntheses of the major Amaryllidaceae alkaloids, all based on the key enzymatic dioxygenation of suitable aromatic precursors. This paper discusses the logic of general synthetic design for lycoricidine, narciclasine, pancratistatin, and 7-deoxypancratistatin. Experimental details are provided for the recently accomplished syntheses of narciclasine, ent-7-deoxypancratistatin, and 10b-epi-deoxypancratistatin via a new and selective opening of a cyclic sulfate over aziridines followed by aza-Payne rearrangement. The structural core of 7-deoxypancratistatin has also been degraded to a series of intermediates in which the amino inositol unit is cleaved and deoxygenated in a homologous fashion. These truncated derivatives and the compounds from the synthesis of the unnatural derivatives have been tested against six important human cancer cell lines in an effort to further develop the understanding of the mode of action for the most active congener in this group, pancratistatin. The results of the biological activity testing as well as experimental, spectral, and analytical data are provided in this manuscript for all relevant compounds.

Studies on the narciclasine alkaloids: Total synthesis of (+)- narciclasine and (+)-pancratistatin

Enantioselective total syntheses of the antimmor alkaloids, (+)- narciclasine and (+)-pancratistatin, are reported. These syntheses feature a stereo- and regiocontrolled aryl enamide photocyclization to construct a common, advanced intermediate possessing a transfused BC substructure. Differential functional group interchange in the C-ring of this phenanthridone core structure allows for the production of the two target natural products in enantiomerically pure form.

A short chemoenzymatic synthesis of (+)-narciclasine

The title alkaloid has been synthesized in eight operations from dibromobenzene and ovanillin, via enzymatic oxidation of the former compound, Suzuki coupling and a Bischler-Napieralski type cyclization as the key transformations.

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.