Enantioselective Synthesis of Xanthatin

• Published in: Chemistry : a European journal Vol. 20; no. 25; pp. 7613 - 7615
• Main Authors: Bergmann, Andreas, Reiser, Oliver
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 16.06.2014; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: allylic oxidation; Antibiotics; Carbonyl compounds; Carbonyls; Chemistry; Chemistry, Multidisciplinary; Derivatives; Enantiomers; exo-methylene group; Furans - chemical synthesis; Furans - chemistry; Furoic acid; Masking; Olefins; Oxidation-Reduction; Physical Sciences; Science & Technology; Sesquiterpenes; Stereoisomerism; Strategy; Synthesis; synthetic methods; total synthesis; xanthanolides; ASYMMETRIC-SYNTHESIS; allylic oxidation; exo-methylene group; total synthesis; xanthanolides; EXTRACTS; DERIVATIVES; synthetic methods
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201402735

The enantioselective synthesis of cytostatic and antibiotic xanthatin (1 a) is reported. As a key intermediate, a bicyclic compound 2 was identified, which can be readily synthesized from methyl‐2‐furoic acid in diastereo‐ and enantiomerically pure form. Compound 2 can be functionalized regio‐ and stereoselectively at C‐6 and C‐7, allowing the facile introduction of the functionalities found in xanthatin, as well as the synthesis of derivatives thereof. Moreover, a robust strategy for the introduction of the exo‐methylene group at C‐3, commonly found in many sesquiterpenes, was developed that makes use of masking the alkene in the α,β‐unsaturated carbonyl system by O‐pivaoyl, which is stable under acidic and mild basic conditions but eliminated upon treatment with strong bases. Organic hardcore: The enantioselective synthesis of cytostatic and antibiotic xanthatin is reported. As a key intermediate, the bicyclic compound A was identified (see scheme), which can be readily synthesized from 2‐furoic acid in diastereo‐ and enantiomerically pure form. Moreover, a new strategy for the introduction of the exo‐methylene group at C‐3, commonly found in many sesquiterpenes, was developed.