20316-18-1Relevant academic research and scientific papers
One-Carbon Insertion and Polarity Inversion Enabled a Pyrrole Strategy to the Total Syntheses of Pyridine-Containing Lycopodium Alkaloids: Complanadine A and Lycodine
Ma, Donghui,Martin, Brandon S.,Gallagher, Katelyn S.,Saito, Takeru,Dai, Mingji
supporting information, p. 16383 - 16387 (2021/10/20)
Complanadine A and lycodine are representative members of the Lycopodium alkaloids with a characteristic pyridine-containing tetracyclic skeleton. Complanadine A has demonstrated promising neurotrophic activity and potential for persistent pain management. Herein we report a pyrrole strategy enabled by one-carbon insertion and polarity inversion for concise total syntheses of complanadine A and lycodine. The use of a pyrrole as the pyridine precursor allowed the rapid construction of their tetracyclic skeleton via a one-pot Staudinger reduction, amine-ketone condensation, and Mannich-type cyclization. The pyrrole group was then converted to the desired pyridine by the Ciamician-Dennstedt rearrangement via a one-carbon insertion process, which also simultaneously introduced a chloride at C3 for the next C-H arylation. Other key steps include a direct anti-Markovnikov hydroazidation, a Mukaiyama-Michael addition, and a Paal-Knorr pyrrole synthesis. Lycodine and complanadine A were prepared in 8 and 11 steps, respectively, from a readily available known compound.
Competent Route to Unsymmetric Dimer Architectures: Total Syntheses of (?)-Lycodine and (?)-Complanadines A and B, and Evaluation of Their Neurite Outgrowth Activities
Zhao, Le,Tsukano, Chihiro,Kwon, Eunsang,Shirakawa, Hisashi,Kaneko, Shuji,Takemoto, Yoshiji,Hirama, Masahiro
, p. 802 - 812 (2017/02/05)
Valuable synthetic routes to the Lycopodium alkaloid lycodine (1) and its unsymmetric dimers, complanadines A (4) and B (5), have been developed. Regioselective construction of the bicyclo[3.3.1]nonane core structure of lycodine was achieved by a remote functionality-controlled Diels–Alder reaction and subsequent intramolecular Mizoroki–Heck reaction. A key coupling reaction of the lycodine units, pyridine N-oxide (66) and aryl bromide (65), through C?H arylation at the C1 position of 66 provided the unsymmetric dimer structure at a late stage of the synthesis. This strategy greatly simplified the construction of the dimeric architecture and functionalization. Complanadines A (4) and B (5) were synthesized by adjusting the oxidation level of the bipyridine mono-N-oxide (67). The diverse utility of this common intermediate (67) suggests a possible biosynthetic pathway of complanadines in Nature. Both enantiomers of lycodine (1) and complanadines A (4) and B (5) were prepared in sufficient quantities for biological evaluation. The effect on neuron differentiation of PC-12 cells upon treatment with culture medium, in which human astrocytoma cells had been cultured in the presence of 1, 4, or 5 was evaluated.
Complanadine A, a selective agonist for the Mas-related G protein-coupled receptor X2
Johnson, Trevor,Siegel, Dionicio
, p. 3512 - 3515 (2014/07/22)
The first biological target for the natural product complanadine A has been determined. The pseudosymmetric alkaloid functions as a selective agonist for the Mas-related G protein-coupled receptor X2 (MrgprX2), a G protein-coupled receptor that is highly expressed in neurons. Given the potential of MrgprX2 to function as a modulator of pain, complanadine A represents a new chemical probe to selectively interrogate the physiological function of MrgprX2 as well as a potential lead for the development of antihyperalgesics for the treatment of persistent pain. While complanadine A possess agonistic activity the related natural product lycodine, representing half of complanadine A, lacks activity providing a cursory description of the structural requirements for agonistic activity.
Biogenetically inspired total syntheses of lycopodium alkaloids, (+)-flabellidine and (-)-lycodine
Azuma, Masayuki,Yoshikawa, Tetsuya,Kogure, Noriyuki,Kitajima, Mariko,Takayama, Hiromitsu
supporting information, p. 11618 - 11621 (2014/11/08)
The first asymmetric total synthesis of (+)-flabellidine (2) and the shortest total synthesis of (-)-lycodine (3) were accomplished by a strategy featuring the one-pot construction of a tetracyclic lycodine skeleton from a linear precursor, which was insp
Syntheses of (+)-complanadine A and lycodine derivatives by regioselective [2 + 2 + 2] cycloadditions
Yuan, Changxia,Chang, Chih-Tsung,Siegel, Dionicio
, p. 5647 - 5668 (2013/07/26)
The dimeric alkaloid complanadine A has shown promise in regenerative science, promoting neuronal growth by inducing the secretion of growth factors from glial cells. Through the use of tandem, cobalt-mediated [2 + 2 + 2] cycloaddition reactions, two synthetic routes have been developed with different sequences for the formation of the unsymmetric bipyridyl core. The regioselective formation of each of the pyridines was achieved based on the inherent selectivity of the molecules or by reversing the regioselectivity through the addition of Lewis bases. This strategy has been successfully employed to provide laboratory access to complanadine A as well as structurally related compounds possessing the lycodine core.
Total syntheses of complanadines A and B
Zhao, Le,Tsukano, Chihiro,Kwon, Eunsang,Takemoto, Yoshiji,Hirama, Masahiro
supporting information, p. 1722 - 1725 (2013/04/10)
Twice as nice: Total syntheses of dimeric alkaloids, (-)-complanadines A (1) and B (2), were achieved from (-)-lycodine. The unsymmetrical motif was assembled through direct arylation of the pyridine N-oxide. The absolute configuration and specific rotations of complanadines A and B were identified. Cbz=Benzyloxycarbonyl. Copyright
