Total Syntheses of (+)- and (−)-Pestalotiopsin A

• Published in: Journal of organic chemistry Vol. 74; no. 17; pp. 6452 - 6461
• Main Authors: Takao, Ken-ichi, Hayakawa, Nobuhiko, Yamada, Reo, Yamaguchi, Taro, Saegusa, Hiroshi, Uchida, Masatoshi, Samejima, Suguru, Tadano, Kin-ichi
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 04.09.2009; Amer Chemical Soc
• Subjects: Aldehydes - chemistry; Alicyclic compounds, terpenoids, prostaglandins, steroids; Catalysis; Chemistry; Chemistry, Organic; Chemistry, Organic - methods; Cyclization; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Inhibitory Concentration 50; Lactones - chemistry; Models, Chemical; Molecular Structure; Organic chemistry; Palladium - chemistry; Physical Sciences; Preparations and properties; Science & Technology; Sesquiterpenes - chemical synthesis; Sesquiterpenes - chemistry; Stereoisomerism; Terpenoids; X-Ray Diffraction; SECONDARY ALCOHOLS; DESS-MARTIN PERIODINANE; ORGANIC-SYNTHESIS; CYCLOBUTANE DERIVATIVES; ENDOPHYTIC FUNGUS; STEREOCONTROLLED APPROACH; TRIMETHYLSILYL ACETALS; SAMARIUM(II)-MEDIATED 4-EXO-TRIG CYCLIZATION; RING CONTRACTION; PESTALOTIOPSIN-A; Enantioselectivity; Palladium complex; Hydrides; Oxygen heterocycle; Allylic compound; Ketenes; Aldol condensation; Chemical reduction; Stereoselectivity; Acetal; Functionalization; Enantiomer; Sesquiterpenes; Chemical synthesis; Intramolecular reaction; Sulfur nitrogen heterocycle; Terpenoid; Catalytic reaction; Hydrocarbon; Lactone; Aldehyde; Total synthesis; Cycloaddition; Sultam; Absolute configuration; Protonation; Nozaki-Hiyama coupling
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo9012546

An enantioselective total synthesis of both enantiomers of caryophyllene-type sesquiterpenoid pestalotiopsin A has been achieved, thereby establishing the absolute stereochemistry of natural (+)-pestalotiopsin A. Highlights of the synthesis include a [2 + 2] cycloaddition of N-propioloyl Oppolzer’s camphorsultam and ketene dialkyl acetal and subsequent highly stereoselective 1,4-hydride addition/protonation, an aldol reaction of functionalized bicyclic lactone with aldehyde, an efficient intramolecular Nozaki−Hiyama−Kishi (NHK) reaction for the construction of the highly strained (E)-cyclononene ring, and a palladium-catalyzed reduction of allylic mesylate with retention of the E configuration.