β-Phenylethylamines and the isoquinoline alkaloids (July 1999 to June 2000)

Direct and Efficient C(sp3)–H Functionalization of N-Acyl/Sulfonyl Tetrahydroisoquinolines (THIQs) With Electron-Rich Nucleophiles via 2,3-Dichloro-5,6-Dicyano-1,4-Benzoquinone (DDQ) Oxidation

“…C(1)-Substituted 1,2,3,4-tetrahydroisoquinolines (THIQs) constitute an important family of biologically active alkaloids, and their derivatives are found as major structural motifs in a wide range of natural products as well as medicines such as (–)-ecteinascidin 743 (Yondelis®, 1 , anti-tumor activity) (Rinehart, 2000 ), (–)-emetine ( 2 , treatment of amoebiasis and amebic dysentery) (Akinboye and Bakare, 2011 ), and (–)-noscapine ( 3 ,anti-tussive agent) (Segal et al, 1957 ) ( Figure 1 ). Not surprisingly, natural and synthetic C(1)-substituted 1,2,3,4-THIQs have attracted much interest from synthetic organic as well as medicinal chemists due to their interesting structural features, in conjunction with a diverse range of biological activities (Bentley, 2001 ; Scott and Williams, 2002 ; Chrzanowska and Rozwadowska, 2004 ), and the development of a new and efficient strategy toward the construction of the C(1)-substituted 1,2,3,4-THIQs still remains imperative.…”

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

“…Pyridones and isoquinolones are relevant heterocyclic scaffolds present in numerous bioactive compounds and natural products [1–4]. Similarly, molecules containing a tetrazole ring exhibit a wide variety of pharmacological and antimicrobial properties [5–6], including analgesic, antihypertensive, anti-inflammatory, anticancer, antifungal and antimalarial activity (Fig.…”

Directed (R)‐ or (S)‐Selective Dynamic Kinetic Enzymatic Hydrolysis of 1,2,3,4‐Tetrahydroisoquinoline‐1‐carboxylic Esters

“…[6] The replacement of amino acids with conformationally constrained analogues allows elucidation of the minimum conformational requirements for biological activity and the selectivity for different targets can be increased. [7] Most isoquinoline alkaloids with broad therapeutic applications contain 6,7-dimethoxy or 6,7-methylenedioxy moieties (e.g., papaverine, noscapine, emetine, atracurium and mivacurium), [8] which make the molecules less hydrophobic and therefore more drug-like. 6,7-Dimethoxy-1-TIC has been applied in the synthesis of β-site amyloid precursor protein-cleaving enzyme inhibitors, which are useful in Alzheimer's disease.…”