Structurally diverse isoquinolines

The quinolines, isoquinolines, and pyridines are structurally diverse with a large number of alkyl-substituted isomers. Direct isotopic measurements have not been made on nitrogen heterocycles. 

The Papaveraceae family is the most inq>ortant source of the QBA. This femily is known as a taxonomic group very rich in isoquinoline alkaloids of great structural diversity [3,4,7] which are biogenetically derived from phenylalanine and tyrosine. The QBA are distributed almost throughout the whole family in a number of genera and species [7] in both the subfamilies Hypecoideae (sometimes considered as an independent family Hypecoaceae) and Papaveroideae Papaveraceae s.str.) with only a few exceptions. In the papaveraceous plants, the alkaloids are localized in lactiferous vessels. 

The Rutaceae are known as a large plant frunUy with approximately ISO genera and 1,000 to 2,000 swedes, chemically characterized by numerous alkaloids of extensive structural diversity. Some isoquinoline alkaloids are known in this family of which especially aporphines, protopines, protoberberines, and benzo[c]phenanthridines are common in the Papave-... 

Ketenes are mostly used as common starting materials for structurally diverse mono-spiro- and fused six-membered heterocycles such as lactones, pyrans, pyronones, pyridines, quinolines, isoquinolines, oxazine, quinoxalines, thiazines, oxathines, etc. 

Cyclization of oximes and diazo compounds via Rh(III)-catalyzed C-H activation provided substituted isoquinoline and pyridine Af-oxides (Scheme 63) (13JA12204). A number of ketones (including those with some steric hindrance) were transformed into oximes that would undergo cyclization. Also, structural diversity, including both electron-donating and... 

The Pictet-Spengler reaction has been carried out on various solid support materials " and with microwave irradiation activation.Diverse structural analogues of (-)-Saframycin A have been prepared by carrying out the Pictet-Spengler isoquinoline synthesis on substrates attached to a polystyrene support. Amine 20 was condensed with aldehyde 21 followed by cyclization to give predominantly the cis isomer tetrahydroisoquinoline 22 which was further elaborated to (-)-Saframycin A analogues. 

As a result of research over the past 20 years (Facchini, 2001 Ziegler et al, 2006 Sato et al, 2007 Zenk and Juenger, 2007 Liscombe and Facchini, 2008 Ziegler and Facchini, 2008), it is now clear that the first committed step in the biosynthesis of isoquinoline is the formation of (S)-norcoclaurine (Fig. 2.5). This alkaloid is an important precursor of a variety of pathways that lead to a series of diverse structures within this alkaloid group. 

The thesis results have already inspired further work in progress on efficient synthesis of indoles and isoquinolines, and his findings would contribute to the diversity-oriented synthesis for the drug discovery and facUe synthesis of biologically active natural products containing complex structure. 1 hope his outstanding thesis will contribute to synthetic research of many readers. 

---