Synthesis of 1‐Substituted Tetrahydroisoquinolines by Lithiation and Electrophilic Quenching Guided by In Situ IR and NMR Spectroscopy and Application to the Synthesis of Salsolidine,Carnegine and Laudanosine

The lithiation of N‐tert‐butoxycarbonyl (N‐Boc)‐1,2,3,4‐tetrahydroisoquinoline was optimized by in situ IR (ReactIR) spectroscopy. Optimum conditions were found by using n‐butyllithium in THF at ?50 °C for less than 5 min. The intermediate organolithium was quenched with electrophiles to give 1‐substituted 1,2,3,4‐tetrahydroisoquinolines. Monitoring the lithiation by IR or NMR spectroscopy showed that one rotamer reacts quickly and the barrier to rotation of the Boc group was determined by variable‐temperature NMR spectroscopy and found to be about 60.8 kJ mol^?1, equating to a half‐life for rotation of approximately 30 s at ?50 °C. The use of (?)‐sparteine as a ligand led to low levels of enantioselectivity after electrophilic quenching and the “poor man’s Hoffmann test” indicated that the organolithium was configurationally unstable. The chemistry was applied to N‐Boc‐6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline and led to the efficient synthesis of the racemic alkaloids salsolidine, carnegine, norlaudanosine and laudanosine.     

A Theoretical Investigation on the Strecker Reaction Catalyzed by a TiIV‐Complex Catalyst Generated from a Cinchona Alkaloid,Achiral Substituted 2,2′‐Biphenol,and Tetraisopropyl Titanate

The mechanism and the origin of selectivity of the asymmetric Strecker reaction catalyzed by a Ti^IV‐complex catalyst generated from a cinchona alkaloid, achiral substituted 2,2′‐biphenol, and tetraisopropyl titanate have been investigated by DFT and ONIOM methods. The calculations indicate that the reaction proceeds through a dual activation mechanism, in which Ti^IV acts as Lewis acid to activate the electrophile aldimine substrate, whereas the tertiary amine in cinchona alkaloid works as Lewis base to promote the activation and isomerization of HCN. The C? C bond formation step is predicted to be the selectivity‐controlling step in the reaction with an energy barrier of 9.3 kcal mol^?1. The “asymmetric activation” is achieved by the transfer of asymmetry from the chiral cinchonine ligand to the axially flexible achiral biphenol ligand through coordination interaction with the central metal Ti^IV. The large steric hindrance from the 3,3′‐position substitute of biphenol, combined with the quinoline fragment of cinchona alkaloid and the orientation of hydrogen bonding of iPrOH, play a key role in controlling the stereoselectivity, which is in good agreement with the experimental observations.     

Alkaloids from Stems of Ervatamia yunnanensis （Ⅱ）

Six indole alkaloids were isolated from the stems of Ervatamia yunnanensis. Among them, 10-hydroxy-19, 20-dihydroisositsirikine （I） is new. The other five are known alkaloids, namely： matrine （Ⅱ）, 19, 20-dihydroisositsirikine （Ⅲ）, 19-s-voacangarine （Ⅳ）, 1 l＇-methoxyl-19s- heyneanine （Ⅴ）, conodurine （Ⅵ）. The structural elucidation of the alkaloids was based on spectral means.     

Alkaloids of Delphinium poltoratskii

Roots ofDelphinium poltoratskiiyield the known alkaloids methyllycaconitine, lycoctonine, anthranoyllycoctonine, ajacine, karacoline, and a new alkaloid delpoline, the structure of which was proved by spectral data and a direct correlation with karacoline. It has been found that the roots and the aerial part of the plant can provide raw material for the production of methyllycaconitine.     

Cimicifine A: A Novel Triterpene Alkaloid from the Rhizomes of Cimicifuga foetida

Cimicifine A ( 1 ), the first cycloartane triterpene alkaloid, was isolated from the rhizomes of Cimicifuga foetida, together with the known compound cimicifugoside H‐1 ( 2 ). Their chemical structures were established by extensive NMR and MS analyses and by comparison with literature.     

Flabelliformides A and B,Two Novel Indole Alkaloids from Ervatamia flabelliformis

Flabelliformides A ( 1 ) and B ( 2 ), containing a novel C₂₀ indole core, have been isolated from the stems of Ervatamia flabelliformis. The structures of 1 and 2 were elucidated on the basis of spectral analysis and X‐ray crystallography.     

苦参生物成碱的二维核磁共振谱(2D-NMR)研究Ⅰ.中国东北产苦参中的N-甲基金雀儿碱与氧化槐根碱的2D-NMR研究

由我国东北产的苦参中分离出七种生物碱。由MS、IR及2D-NMR鉴定为:(+)-苦参碱、(+)-氧化苦参碱、5α-羟基苦参碱、N-甲基金雀儿碱、9α-羟基苦参碱及氧化槐根碱。另一个生物碱(6)的化学结构尚在鉴定之中。本课题采用了二种2D-NMR技术,H-H相关谱(300、400及500MHz)及C-H相关谱(H:300MHz;C:75MHz)。先发表其中两个生物碱的2D-NMR,其它将陆续发表。     

Synthesis of (+)-(1R,2S,9S,9aR)-octahydro-1H-pyrrolo[1,2-a]azepine-1,2,9-triol: a potential glycosidase inhibitor

The title compound was prepared as a potential glycosidase inhibitor. Key steps in the synthesis are vinyl epoxide aminolysis, ring-closing metathesis, cis-dihydroxylation and then ring closure.     

Syntheses of the antibiotic alkaloids renierone, mimocin, renierol, renierol acetate, renierol propionate, and 7-methoxy-1,6-dimethylisoquinoline-5,8-dione

The total synthesis of renierone, mimocin, renierol, renierol acetate, renierol propionate, and 7-methoxy-1,6-dimethylisoquinoline-5,8-dione was successfully achieved by the regioselective oxidation of 5-oxygenated isoquinoline. The synthetic method of the 5-oxygenated isoquinoline is based on the thermal electrocyclic reaction of 1-azahexatriene system involving the benzene 1,2-bond.