Addition of Indole to Methyl 2‐Chloro‐2‐cyclopropylideneacetate en Route to Spirocyclopropanated Analogues of Demethoxyfumitremorgine C and Tadalafil | Zendy

Limbach Michael | Zendy; Dalai Suryakanta | Zendy; Janssen André | Zendy; EsSayed Mazen | Zendy; Magull Jörg | Zendy; de Meijere Armin | Zendy

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Addition of Indole to Methyl 2‐Chloro‐2‐cyclopropylideneacetate en Route to Spirocyclopropanated Analogues of Demethoxyfumitremorgine C and Tadalafil

Author(s) -

Limbach Michael,

Dalai Suryakanta,

Janssen André,

EsSayed Mazen,

Magull Jörg,

de Meijere Armin

Publication year - 2005

Publication title -

european journal of organic chemistry

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.825

H-Index - 155

eISSN - 1099-0690

pISSN - 1434-193X

DOI - 10.1002/ejoc.200400617

Subject(s) - chemistry , yield (engineering) , indole test , tadalafil , condensation , hydantoin , stereochemistry , condensation reaction , natural product , tryptophan , medicinal chemistry , organic chemistry , catalysis , amino acid , materials science , medicine , biochemistry , physics , sildenafil , metallurgy , thermodynamics

Indole readily added across the double bond of the highly reactive Michael acceptor methyl 2‐chloro‐2‐cyclopropylideneacetate ( 4 ) to yield 2‐chloro‐2‐(3′‐indolylcyclopropyl)acetate 5 (85%) which was converted in two steps into the racemic tryptophan analogue 7 in 90% yield. This in turn was transformed by a condensation and Pictet−Spengler sequence into the spirocyclopropane analogues, 11 , 13 and 15 , of both the natural product (demethoxy)fumitremorgine C ( 3b , 3 steps, 11% yield) and the potent PDE‐5 inhibitor Tadalafil ( 2 , 3 steps, 71% yield) as well as the original lead structure with a hydantoin backbone ( 1 , 2 steps, 79% yield). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

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