Total Synthesis of 7-Hydroxymurrayazolinine, Murrayamine D, and Mahanine via m-Nitro Group Activated Pyran Annulation

Abstract

The facile total synthesis of the natural product (±)-mahanine was obtained in eight steps with an overall 52% yield from readily accessible known nitrophenol derivative 6. After a one-step, acid-catalyzed annulation, two additional natural products were formed including 7-hydroxymurrayazolinine, representing its first reported total synthesis. In the whole process, the introduction of the m-nitro group significantly enhanced the key pyran annulation reaction through inductive effects.

Influence of Geographical and Seasonal Variations on Carbazole Alkaloids Distribution in Murraya koenigii: Deciding Factor of Its In Vitro and In Vivo Efficacies against Cancer Cells

“…Here, we have isolated the mahanine and mahanimbine using the reference compounds, and purity was confirmed by HPLC ( Figure S1). ESI-MS ( Figure S2), 1 H ( Figure S3), and 13 C NMR spectral data analyses established their structures as mahanine and mahanimbine (Figure 1(b)). During this process, we have also isolated another carbazole alkaloid, koenimbine, and characterization was again confirmed by HPLC, ESI-MS, NMR, and compared with the available literature (PubChem CID: 97487).…”

“…Mahanine and mahanimbine were further purified by preparative TLC and HPLC using a reverse-phase C18 column to get ≥95% purity. Purification was confirmed by thin layer chromatography (TLC), high pressure liquuid chromatography (HPLC), and mass spectrometry (ESI-Q TOF instrument), and the structure was confirmed by 1 H Nuclear magnetic resonance (NMR) and 13 C NMR (Bruker 600 MHz and JEOL 400 MHz instruments) [4]. Koenimbine-containing fraction was washed thrice with methanol to yield pure compound and characterized similarly.…”

“…Even after two decades of the discovery of mahanine, the synthesis of this alkaloid is very difficult even today. Very recently, Hou et al reported the synthesis of (±) mahanine involving eight steps with lesser yield [13]. is synthetic mahanine is expected to be less active as it is a mixer of two enantiomers.…”

Molecules targeting the androgen receptor (AR) signaling axis beyond the AR‐Ligand binding domain

“…While these data do not indicate the inhibition of AR signaling by mahanine is exclusively dependent on a CDK1‐mediated pathway, it is noteworthy since CDK1 activity is commonly elevated in CRPC . Given the ready natural availability and the possibility to devise an efficient total synthesis, mahanine and its derivatives hold some promise to be developed further . Its effects on multiple signaling pathways, however, raise questions about specificity and underlying mechanism(s) of action.…”

Microwave Assisted One-Pot Three-Component Synthesis of Novel Pyranocarbazole Derivatives as Antiproliferative Agents and Molecular Docking Studies

“…Methods using domino aldol type/6π-electrocyclization, palladium catalyzed intramolecular C-O and C-C cross-coupling reaction [20] and iron-mediated oxidative cyclization [21] are common. Palladium(II)-catalyzed carbazole construction followed by pyran ring annulations [23,[25][26][27][28], hexahydro-Diels-Alder reaction [32] and other methods have also been used [33][34][35][36][37]. Recently, we have developed a simple and efficient one-pot synthetic approach to pyrano [3,2-c]carbazole derivatives [38].…”