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Totalsynthese von Isokalafunginen und Isonanaomycinen
Author(s) -
Hoffmann Bernd,
Schönebaum Andreas,
Lackner Helmut
Publication year - 1993
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.199319930157
Subject(s) - chemistry , stereochemistry , diastereomer , ring (chemistry) , chirality (physics) , total synthesis , organic chemistry , chiral symmetry , physics , quantum mechanics , nambu–jona lasinio model , quark
Total Synthesis of Isokalafungins and Isonanaomycins The total synthesis of isokalafungins ( 2 ) and isonanaomycins ( 12 ), the first members of a nonnatural group of benzoisochromanquinone antibiotics hydroxylated only at C‐6, is described. Pathway A (Scheme 1) yields the separated (±)‐ cis and ‐ trans diastereomers of 2 and 12 and is especially suited for modifications of the dihydropyrane ring. On pathway B the chirality of C‐1 is preformed by using 3,4,6‐trideoxy‐α‐ L ‐glycero‐hex‐3‐enopyranosid‐2‐ulose ( 22 ) as a main building block, for the first time synthesized from L ‐fucose (Scheme 2). According to Scheme 3, condensation of 22 with the intermediate 23 gives the new 6‐hydroxylated variants (1 S ,3 S ,4 S )‐isonanaomycin D ( 30 ) and (1 R ,3 R ,4 R )‐isokalafungin ( 2 ). Pathway B favours modifications of the phenolic ring, which can strongly influence the spectrum of activity. Unexpectedly, the shifting of the hydroxy group from C‐9 to C‐6 changes the antibacterial properties unessentially.