Premium
Total Synthesis of the Tolypothrix Pentaether via A Bis(γ‐butyrolactone) → 1,3,7,9‐Tetraol Route
Author(s) -
Allerheiligen Swen,
Brückner Reinhard
Publication year - 1997
Publication title -
liebigs annalen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0947-3440
DOI - 10.1002/jlac.199719970807
Subject(s) - chemistry , acetonide , stereocenter , epoxide , total synthesis , lactone , olefin fiber , ether , stereochemistry , bromide , alcohol , organic chemistry , enantioselective synthesis , catalysis , medicine , surgery , triamcinolone acetonide
Abstract A total synthesis of the permethylether 1 from Tolypothrix conglutinata via a bis (γ‐lactone) intermediate was achieved. It constitutes a methodological complement of our previous syntheses (summarized in Scheme 7) of the same ether via mono (γ‐lactones) as key intermediates. The readily available γ‐lactone 4 and the allyl‐bromide containing lactone cis ‐ 13 derived from 4 as shown in Scheme 3 were combined by a cis ‐selective alkylation to the bislactone cis,trans ‐ 14 (Scheme 4). From this bislactone, we removed both carboxylic centers and replaced each of them by a hydroxy group to obtain a single 1,3,7,9‐tetraol. Without purification, this tetraol was protected as bis‐acetonide 15 (Scheme 4; 43% yield over the two steps). In the next three steps the bis‐acetonide olefin 15 was transformed into the bis‐acetonide alcohol 19 (Scheme 5). Compound 19 gave epoxide 21 (Scheme 6) with concomitant inversion of the configuration at the hitherto incorrectly configured stereocenter. Opening the epoxide 21 at the less hindered side with a higher‐order lithium vinyl cyanocuprate, acetonide cleavage, and permethylation of the obtained pentaol finished the synthesis of the target ether 1 (Scheme 6).