Total Synthesis of Erythronolide BSlide Number 2Slide Number 3Retrosynthetic Analysis and Strategy Retrosynthetic Analysis (Continued) Retrosynthetic Analysis (Continued) Total SynthesisSynthesis of compound 17Synthesis of intermediate 11Slide Number 10Slide Number 11Slide Number 12Slide Number 13Slide Number 14Total Synthesis of Erythronolide B Slide Number 16Slide Number 17Slide Number 18Slide Number 19Total Synthesis of Erythronolide BBy Damith PereraCEM 852 Spring 2011Introduction• Erythronolide B is the biosynthetic precursor of all of the Erythromycins.• The land mark total synthesis was performed by E.J Corey and his co-workers at Harvard in the 1970s. • Erythronolide B : 14-membered lactone10 asymmetric carbon atomsCorey-Nicolaou Macrolactonization StrategyRetrosynthetic Analysis and StrategyRetrosynthetic Analysis (Continued)Retrosynthetic Analysis (Continued)Total SynthesisSynthesis of compound 17Synthesis of intermediate 11Synthesis of intermediate 11 (Continued)Synthesis of intermediate (+) - 12Synthesis of intermediate (+) - 12 (Continued)Synthesis of intermediate 8Synthesis of intermediate 8 (Continued)Total Synthesis of Erythronolide BTotal Synthesis of Erythronolide B (Continued)• Bromolactonization : create asymmetric carbons • Corey-Nicolaou double activation method: form large-ring lactone• Mukaiyama’s ketone synthesis: coordinated tetrahedral intermediateConclusionReferences :1. Corey, E.J.; Nicolaou, K.C.; J. Am. Chem. Soc. 1974, 96, 5614.2. Nicolaou, K.C.; Sorenson, E. J. (1996). Classics in Total Synthesis; VCH Publishers. 167-184.Thank you
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