184535-17-9Relevant academic research and scientific papers
Strategies for the Asymmetric Construction of Pelletierine and its Use in the Synthesis of Sedridine, Myrtine, and Lasubine
Zaidan, Raed K.,Evans, Paul
, p. 5354 - 5367 (2019/06/25)
Three methods for the asymmetric synthesis of both enantiomers of pelletierine 6 are reported. Bella's proline-based Mannich process gave (R)- and (S)-Cbz-protected 6 in good yields from Δ1-piperideine 14 and in reasonable enantiomeric excess (74–80 % ee). An intramolecular aza-Michael, cinchona-based, organocatalytic method is also reported. With commercially available 9-amino quinine (24a) and quinidine (24b) catalysts, Cbz-protected α,β-unsaturated ketone 23 also gave (R)- and (S)-Cbz-protected 6 in good yields and enantiomeric excess (90–99 % ee). This material was used to synthesize both optically active forms of deoxyhalofuginone (26), an analogue of febrifugine which is of interest as an anti-fibrotic agent. Finally, a resolution of racemic pelletierine using (R)- and (S)-mandelic acid 27 is reported. This scalable method gave both enantiomers of Cbz- and Boc-protected 6 in excellent enantiomeric excess (≥ 99 %). Both highly enantioenriched forms of 6 (obtained from the resolution study) were used to synthesize several alkaloids. Firstly, (–)-(S)-Cbz-protected pelletierine 17 was used to prepare naturally occurring sedridine (32) and its epimer allosedridine (8). Then the preparation of both enantiomers of the quinolizidine myrtine (33) by an olefination-intramolecular aza-Michael sequence is reported. Finally, the synthesis of the epimeric quinolizidine alkaloids, lasubine I (34) and lasubine II (35), from (+)- and (–)-Boc-protected pelletierine (29) respectively, is discussed.
Asymmetric synthesis of (+)- and (-)-deoxyfebrifugine and deoxyhalofuginone
Zaidan, Raed K.,Smullen, Shaun,Evans, Paul
supporting information, p. 6433 - 6435 (2015/11/16)
Both enantiomers of deoxyfebrifugine (4) and deoxyhalofuginone (5), analogues of the quinazolinone-containing biologically active compounds febrifugine (1) and halofuginone (3), have been prepared in a six-step reaction sequence featuring an organocatalyzed Mannich reaction as the key stereo-inducing step. The compounds were isolated as their dihydrobromide salts in 29-42% overall yield and in 74-80% enantiomeric excess.
Henry-Nef reaction: A practical and versatile chiral pool route to 2-substituted pyrrolidine and piperidine alkaloids
Bhat, Chinmay,Tilve, Santosh G.
, p. 6129 - 6143 (2013/07/27)
The paper describes the synergistic protocol developed by combinatorial Henry and Nef reaction for the synthesis of 2-substituted pyrrolidine and piperidine alkaloids containing 1,3-aminoketone and 1,3-amino alcohol units. The utility of the protocol is demonstrated by asymmetric synthesis of 12 natural products of which asymmetric synthesis of (-)-N-methylpelletierine is presented for the first time. The one-carbon homologation described also provides an alternate route for the synthesis of key intermediates homoprolinol and homopipecolinol used as synthetic precursors for several alkaloids and construction of β-amino acids from α-amino acids.
Microwave-assisted organocatalytic enantioselective intramolecular aza-Michael reaction with α,β-unsaturated ketones
Fustero, Santos,Del Pozo, Carlos,Mulet, Cristina,Lazaro, Ruben,Sanchez-Rosello, Maria
supporting information; experimental part, p. 14267 - 14272 (2012/01/07)
An organocatalytic enantioselective intramolecular aza-Michael reaction of carbamates bearing conjugated ketones as Michael acceptors is described. By using 9-amino-9-deoxy-epi-hydroquinine as the catalyst and pentafluoropropionic acid as a co-catalyst, a series of piperidines, pyrrolidines, and the corresponding benzo-fused derivatives (indolines, isoindolines, tetrahydroquinolines, and tetrahydroisoquinolines) can be obtained in excellent yields and enantioselectivities. In addition, the use of microwave irradiation at 60 °C improves the efficiency of the process giving rise to the final products with comparable yields and enantiomeric excesses. Some mechanistic insights are also considered.
Asymmetric organocatalytic intramolecular aza-michael addition of enone carbamates: Catalytic enantioselective access to functionalized 2-substituted piperidines
Liu, Jian-Dong,Chen, Ying-Chun,Zhang, Guo-Biao,Li, Zhi-Qiang,Chen, Peng,Du, Ji-Yuan,Tu, Yong-Qiang,Fan, Chun-An
, p. 2721 - 2730 (2011/12/04)
The synthetically useful functionalized 2-substituted piperidines containing a lateral ketone group have been strategically accessed via an organocatalytic enantioselective intramolecular aza-Michael addition of enone carbamates, in which a novel internal substrate combination of the enone moiety as Michael acceptor and the carbamate moiety as Michael donor was revealed in asymmetric bifunctional organocatalysis. This heteroatom conjugate addition, which was realized by using a catalytic chiral Cinchona-based primary-tertiary diamine and an achiral Bronsted acid, mostly proceeded in high yield and good to excellent stereocontrol (up to 99% ee). This reaction provides an alternative catalytic asymmetric method for installing the stereogenic nitrogen-containing carbon center in functionalized 2-substituted piperidines, leading to the development of a straightforward and expeditious synthesis of some naturally occurring bioactive 2-substituted piperidine alkaloids. Copyright
