synthesis and catalytic functionalization of biologically active indoles

1 Palladium-catalyzed Coupling Reactions of Indoles 2
Clearly, the development of novel methods for the synthesis of indoles is
stimulated by their widespread utility in life science. [2] Over the last century the
preparation and functionalization of indoles continued to be an important object of
research. Today, a range of well-established “classical” methods are available.
Typical examples include the Fischer indole synthesis, the Gassman synthesis,
the Madelung cyclization, the Bischler indole synthesis and the Batcho-Leimgruber
synthesis. [3]
Table 1. Selected indole drugs and their medical indication.
Name Domain Drug
a Sumatriptan migraine headaches, hypertonia Imigran ®
b Melatonin hormone, primary insomnia Circadin ®
c Tryptophan epilepsy, depression L-Tryptophanratiopharm
®,
Ardeydorm ®
d Pergolid Parkinson’s disease Parkotil ®
e Lisurid Parkinson’s disease,
migraine headaches
Dopergin ®
f Reserpin hypertension Briserin ®
g Vincristine cancer chemotherapy Oncovin ®
h Ergotamin migraine headaches Ergo-Kranit ®
I Ajmalin cardiac arrhythmia Gilurytmal ®
j Yohimbin hypertension, aphrodisiac Yocon-Glenwood ®
Yocon ® ,
Yohimbin Spiegel ®
In addition, a variety of more modern transition metal-based syntheses and
domino reactions have been developed. In general, the availability of starting
materials and the functional group tolerance defines the suitability of the
respective indole synthesis. [4]
In the last two decades transition metal-catalyzed coupling reactions have
dramatically improved the synthesis of biologically active molecules. [5]