29477-83-6Relevant articles and documents
ISOCARBOSTYRIL ALKALOIDS AND FUNCTIONALIZATION THEREOF
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Page/Page column 82; 87; 88, (2020/07/04)
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
Borra, Suresh,Lapinskaite, Ringaile,Kempthorne, Christine,Liscombe, David,McNulty, James,Hudlicky, Tomas
, p. 1451 - 1459 (2018/07/13)
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
Elango, Shanmugham,Yan, Tu-Hsin
, p. 6954 - 6959 (2007/10/03)
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%.
