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Synthesis of L ‐Furanomycin and Its Analogues via Furoisoxazolines
Author(s) -
Zimmermann Peter J.,
Lee Ja Young,
Hlobilova née Blanarikova Iva,
Endermann Rainer,
Häbich Dieter,
Jäger Volker
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.200500148
Subject(s) - chemistry , nitrile , epoxide , dimethyldioxirane , hydroboration , bicyclic molecule , stereoselectivity , epimer , nucleophile , stereochemistry , cycloaddition , enantioselective synthesis , nucleophilic addition , derivative (finance) , organic chemistry , catalysis , financial economics , economics
The 1,3‐dipolar cycloaddition of nitrile oxides and 2‐methylfuran has provided suitable precursors for α‐amino acids such as L ‐furanomycin ( 1 ) that contain a dihydrofuran ring. By using a chiral nitrile oxide derived from D ‐glyceraldehyde, the enantiomerically pure furoisoxazolines 9 and 10 were obtained. Owing to the bicyclic, bowl‐shaped structure of furoisoxazoline 9 highly stereoselective additions were feasible, in particular, the epoxidation of 9 with dimethyldioxirane provided the required (5' S ) configuration in 1 after epoxide reduction. Hydroboration of 9 led to the (5' R ) epimer 2 and nucleophilic addition of a methyl Grignard reagent to epoxyfuroisoxazoline 11 gave rise to 5'‐methylfuranomycin ( 3 ). Further, catalytic hydrogenation of the dihydrofuran intermediate 22 , derived from 11 , afforded the tetrahydrofuranyl derivative 31 from which dihydrofuranomycin ( 4 ) was obtained in enantiomerically pure form. The biological activities of these α‐amino acids showed an extremely narrow structure–activity profile, the natural product being the only compound of this series with high activities. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)