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Selektive Reaktionen an Cytochalasin D
Author(s) -
Chappuis Georges,
Tamm Christoph
Publication year - 1982
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19820650210
Subject(s) - chemistry , double bond , ozonolysis , allylic rearrangement , bond cleavage , sharpless epoxidation , stereochemistry , isomerization , acetic acid , triethylamine , medicinal chemistry , epoxide , organic chemistry , catalysis
In connection with the total synthesis of cytochalasans the cleavage of the macrocyclic system of cytochalasin D ( 3 ) was studied in order to gain useful relay compounds. Selective scission of the double bond in 19‐position was achieved by controlled ozonolysis leading to compound 7 ( Scheme 1 ). Treatment of 3 with OsO 4 and subsequent acetylation gave the tetraacetoxy‐ and diacetoxy derivatives 8 and 9 , respectively. Sharpless epoxidation of 3 yielded the mono‐, di‐ and the two epimeric triepoxides 10 , 11 , 12 , and 13 , respectively. Further studies concerned the isomerization of the 6(12)‐double bond to 6(7)‐double bond by an allylic rearrangement. Treatment of 3 with mesylchloride and triethylamine led to 12‐hydroxy‐, 12‐mesyloxy‐ and 12‐chlorozygosporin ( 14 , 16 , and 17 , resp.) (see Scheme 2 ). Epoxidation of 14 gave a mixture of the two epimeric 6,7‐epoxides 21 and 23. Zn‐reduction of 18 (the corresponding bromide of 17 ) led to zygosporin G ( 20 ). In order to convert a carbocyclic cytochalasan into a macrocyclic derivative, 3 was converted to 32 ( Scheme 2 ). Treatment of 32 with H 2 O 2 in acetic acid/chloroform or with phenylselenylperacid/H 2 O 2 yielded the enollactone 33 . Finally, 17,18‐secocytochalasin D derivatives were prepared for the synthesis of unnatural analogs of macrolidic cytochalasans. The diol 26 was converted into the ketoaldehydes 38 and 40 and to the corresponding keto‐acids 43 and 44 ( Scheme 3 ), which were reduced to the ω‐hydroxycarboxylic acids 45 – 48. Treatment of 47 with 2,2 / ‐dipyridyldisulfide/triphenylphosphine/xylene gave probably the lactone 50 .