One-Pot Synthesis of Chromone-Fused Pyrrolo[2,1-a]isoquinolines and Indolizino[8,7-b]indoles: Iodine-Promoted Oxidative [2 + 2 + 1] Annulation of O-Acetylphenoxyacrylates with Tetrahydroisoquinolines and Noreleagnines

2区 · 化学

Article

作者: Qin, Lu-Ying ; Zhang, Hui-Ru ; Wu, An-Xin ; Li, Yi-Ming ; Wu, Rui-Xue ; Zhu, Yan-Ping ; Shang, Zhi-Hao ; Zhang, Xiang-Jin ; Yan, Yu ; Ni, Xue

An iodine-promoted one-pot cascade oxidative annulation reaction has been developed for the synthesis of chromone-fused-pyrrolo[2,1-a]isoquinolines and indolizino[8,7-b]indoles from o-acetylphenoxyacrylates, tetrahydroisoquinolines, and noreleagnines. This process underwent a logical approach to both chromone-fused-pyrrolo[2,1-a]isoquinolines and chromone-fused-indolizino[8,7-b]indoles isolamellarin derivatives. Manipulations of l-menthol and dl-α-tocopherol demonstrate the applications of this strategy.

2020-07-24·Journal of Natural Products

Natural Product-Derived Chiral Pyrrolidine-2,5-diones, Their Molecular Structures and Conversion to Pharmacologically Important Skeletons

Article

作者: Mohan, Chithra ; Habel, Deenamma ; Puente, Andrew R. ; Fritz, Matthew ; Nair, Rani R. ; Abdul, Rinshad V. ; Ibnusaud, Ibrahim ; Nair, Divya S. ; Johnson, Jordan L. ; Haleema, Simimole ; Pillai, Sarath M. ; Gopinath, Chithra ; Kallingathodi, Zabeera ; Polavarapu, Prasad L. ; Thomas, Grace

The versatility of the natural products (2S,3S)- and (2S,3R)-3-hydroxy-5-oxotetrahydrofuran-2,3-dicarboxylic acids (1 and 2), isolated in large amounts from tropical plant sources, has been demonstrated by the construction of 3-substituted and 3,4-disubstituted chiral pyrrolidine-2,5-diones. The absolute configurations of chiral pyrrolidine-2,5-diones have been ascertained using chiroptical spectroscopic methods and/or single-crystal XRD data. A combination of different reaction strategies delivering a diverse matrix of fused heterocyclic ring systems is presented. The pyrrolo[2,1-a]isoquinoline alkaloid (+)-crispine A possesses a wide range of pharmacological activities including antidepressant, antiplatelet, antileukemic, and anticancer activities. The analogues of indolizino[8,7-b]indole alkaloids (+)- and (-)-harmicine show strong antileishmanial, antinociceptive, PDE5-inhibitory, antimalarial, and antiviral activities. The bicyclic furo[2,3-b]pyrrolo skeleton is present in many natural products. Thus, the uniqueness of relatively cheap, naturally occurring chiral 2-hydroxycitric acid lactones as chirons has been demonstrated by the construction of some important molecular skeletons that are otherwise difficult to synthesize.

2017-02-01·European Journal of Medicinal Chemistry1区 · 医学

Novel indolizino[8,7-b]indole hybrids as anti-small cell lung cancer agents: Regioselective modulation of topoisomerase II inhibitory and DNA crosslinking activities

1区 · 医学

Article

作者: Tsann-Long Su ; Anamik Shah ; Ming-Jing Hwang ; Te-Chang Lee ; Yi-Wen Lin ; Tai-Lin Chen ; Dilip Detroja ; Ching-Shu Suen ; Sue-Ming Chang ; Hima Bindu Pidugu ; Ming-Hsi Wu ; Wilson Christian

A novel series of bis(hydroxymethyl)indolizino[8,7-b]indole hybrids composed of β-carboline (topoisomerase I/II inhibition) and bis(hydroxymethyl)pyrrole (DNA cross-linking) are synthesized for antitumor evaluation. Of tumor cell lines tested, small cell lung cancer (SCLC) cell lines are the most sensitive to the newly synthesized compounds. These hybrids induce cell cycle arrest at the G2/M phase, trigger tumor cell apoptotic death, and display diverse mechanisms of action involving topoisomerase II (Topo II) inhibition and induction of DNA cross-linking. Intriguingly, the substituent at N¹¹ (H or Me) plays a critical role in modulating Topo II inhibition and DNA cross-linking activities. N¹¹-Me derivatives predispose to induce DNA crosslinks, whereas N¹¹-H derivatives potently inhibit Topo II. Computational analysis implicates that N¹¹-Me restrict the torsion angles of the two adjacent OH on pyrrole resulting in a favorable of DNA cross-linking. Among these hybrids, compound 17a with N¹¹-H is more effective than cisplatin and etoposide, but as potent as irinotecan, against the growth of SCLC H526 cells in xenograft model.

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