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Total Synthesis of Lingzhiol and its Analogues through the Wittig Reaction of an Oxocyclopentane Carboxylate
Author(s) -
Rengarasu Rathikrishnan,
Maier Martin E.
Publication year - 2017
Publication title -
asian journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.846
H-Index - 44
eISSN - 2193-5815
pISSN - 2193-5807
DOI - 10.1002/ajoc.201600455
Subject(s) - chemistry , wittig reaction , carboxylate , total synthesis , stereochemistry , organic chemistry , combinatorial chemistry
The biosynthesis of polycyclic natural product lingzhiol ( 1 ) through an intramolecular Friedel–Crafts alkylation reaction of an aryl‐substituted cyclopentane epoxide ( 22 ) was attempted. The synthesis of this endocyclic epoxide involved the alkylation of cyclopentane carboxylate 14 with alkyl iodide 25 to afford ketoester 26 . Subsequent Wittig olefination led to exocyclic alkene exo ‐ 15 in good yield. Epoxidation, opening of the epoxide to generate allyl alcohol 29 , and a second epoxidation reaction afforded compounds 22 and 31 . However, presumably owing to stereoelectronic effects, the cyclization of these substrates into polycycles 17 and 32 , respectively, was unsuccessful. Nevertheless, the Wittig reaction to afford exo ‐ 15 allowed us to converge with the previously reported route of Qin et al., which featured the cyclization of spiro epoxide 16 . Thus, lingzhiol is now available in only nine steps. Various analogues of lingzhiol were also prepared, including desoxy derivative 37 , quinone 38 , mono‐methoxy‐deoxy derivative 39 , and ketone 40 .