Sulfogriseofulvin derivatives. synthesis by [4 + 2]cycloaddition, structure, properties, crystal structure analysis, and antifungal activity of spiro[1,3-benzoxathiole-2,1'-cyclohex-2'-en]-4'-one 3,3-dioxides.
Syntheses of substituted, especially of fluoro substituted benzoxathiole 1,1-dioxides, are described. These derivatives were transformed via the Peterson olefination into substituted 2-alkylidene derivatives 27. Diels-Alder reactions of 27 with 1,1-dimethoxy- and 1-methoxy-3-trimethylsiloxy-1,3-butadiene (30, 32) gave sulfone analogues 31 of griseofulvin (named sulfogriseofulvins). From Z-27, a number of cis-isomers with the relative stereochemistry of griseofulvin (cis-31) was prepared, and from E-isomers of 27, compounds (trans-31) with relative stereochemistry of epigriseofulvin were obtained. Some related compounds (33, 38) are synthesized by slight modifications. The stereochemistry is established by spectroscopic methods and crystal structure analyses. The compounds 31 were tested against three species of dermatophytes. The biological activities were all significantly lower than that of griseofulvin.
Friedrich
M
M
Department of Chemistry and Pharmacy, LS Pharmaceutical Chemistry, University of Freiburg, Germany.
Meichle
W
W
Bernhard
H
H
Rihs
G
G
Otto
H H
HH
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013056:Spectrophotometry, Ultraviolet; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D001572:Benzofurans; D001583:Benzoxazoles; D013141:Spiro Compounds