New syntheses of (±)-tashiromine and (±)-epitashiromine via enaminone intermediates

• Darren L. Riley,
• Joseph P. Michael and
• Charles B. de Koning

Beilstein J. Org. Chem. 2016, 12, 2609–2613, doi:10.3762/bjoc.12.256

• of the naturally occurring indolizidine alkaloid (±)-tashiromine and its unnatural epimer (±)-epitashiromine are demonstrated through the use of enaminone chemistry. The impact of various electron-withdrawing substituents at the C-8 position of the indolizidine core on the preparation of the bicyclic

• system is described. Keywords: alkaloid; enaminone; epitashiromine; indolizidine; tashiromine; Introduction Tashiromine (1) is a monosubstituted indolizidine alkaloid originally isolated from the Asian deciduous shrub Maackia tashiroi [1] and subsequently from the genera Poecilanthe [2] and Crotalaria

• /C-8 bond. In this article we describe further extensions to our route to substituted indolizidines, and an application to the synthesis of racemic tashiromine (1) and epitashiromine (2). Results and Discussion One of the most versatile methods for preparing the enaminones of interest is the

Novel stereocontrolled syntheses of tashiromine and epitashiromine

• Loránd Kiss,
• Enikő Forró and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2015, 11, 596–603, doi:10.3762/bjoc.11.66

• stereocontrolled approach has been developed for the syntheses of tashiromine and epitashiromine alkaloids from cyclooctene β-amino acids. The synthetic concept is based on the azetidinone opening of a bicyclic β-lactam, followed by oxidative ring opening through ring C–C double bond and reductive ring-closure

• –cyclization [27], or electrophilic pyrolidinone alkylation followed by ring closure [28][29]. Pyrrolidine alkylation and nucleophilic ring closure followed by C–C double bond hydroboration [30] leads to racemic epitashiromine, as does the N-alkylated succinimide transformation through the corresponding

• indolizidinone [31]. Several synthetic procedures have also been developed for the preparation of tashiromine or epitashiromine enantiomers. (+)-Tashiromine has been synthetized from a pyrrolidinone derivative through chiral Lewis acid-catalysed cyclization to substituted pyrrolidinones [17], by the