title: Asymmetric Total Syntheses of Two 3-Acyl-5,6- dihydro-2H-pyrones: (R)-Podoblastin-S and (R)- Lachnelluloic Acid with Verification of the Absolute Configuration of (-)-Lachnelluloic Acid.
abstract: Expedient asymmetric total syntheses of both (R)-podoblastin-S and (R)-lachnelluloic acid, representative of natural 3-acyl-5,6-dihydro-2H-pyran-2-ones, were performed. Compared with the reported total synthesis of (R)-podoblastin-S (14 steps, overall 5% yield), the present study was achieved in only five steps in an overall 40% yield and with 98% ee (HPLC analysis). In a similar strategy, the first asymmetric total synthesis of the relevant (R)-lachnelluloic acid was achieved in an overall 40% yield with 98% ee (HPLC analysis). The crucial step utilized readily accessible and reliable Soriente and Scettri's Ti(OiPr)₄/(S)-BINOL‒catalyzed asymmetric Mukaiyama aldol addition of 1,3-bis(trimethylsiloxy)diene, derived from ethyl acetoacetate with n-butanal for (R)- podoblastin-S and n-pentanal for (R)-lachnelluloic acid. With the comparison of the specific rotation values between the natural product and the synthetic specimen, the hitherto unknown absolute configuration at the C(6) position of (-)-lachnelluloic acid was unambiguously elucidated as 6R.
authors.affiliation: Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, Sanda, Hyogo 669- 1337, Japan. tt_fujiwara@jp.daicel.com.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fujiwara
authors.affiliation: Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, Sanda, Hyogo 669- 1337, Japan. dzx10859@kwansei.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsutsumi
authors.affiliation: Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, Sanda, Hyogo 669- 1337, Japan. dtp68975@kwansei.ac.jp.
authors.forename: Kohei
authors.initials: K
authors.lastname: Nakata
authors.affiliation: Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, Sanda, Hyogo 669- 1337, Japan. nakatsuji@kwansei.ac.jp.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Nakatsuji
authors.affiliation: Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, Sanda, Hyogo 669- 1337, Japan. tanabe@kwansei.ac.jp.
authors.forename: Yoo
authors.initials: Y
authors.lastname: Tanabe
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000447:Aldehydes; D001688:Biological Products; D011714:Pyrans; D011753:Pyrones; C116609:3-hydroxybutanal; C046012:pentanal
keywords: 1,3-bis(trimethylsiloxy)diene; 3- acyl-5,6-dihydro-2H-pyrones; alternaric acid; asymmetric Mukaiyama aldol reaction; asymmetric total synthesis; lachnelluloic acid; natural fungicide; podoblastin