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Zaragozic Acids: Synthesis of Core, Side Chains and Total Synthesis of the Zaragozic Acid A and C Literature Meeting Presented by Kimberly-Ann Laberge April 17, 2007
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Zaragozic Acids -Characterized by a 4,6,7-trihydroxy-2,8-dioxabicyclo[3,2,1]octane-3,4,5-tricarboxylic acid core with an array of six stereogenic centers including contiguous quaterny ones, with various C1 alkyl and the C6 O-acyl side chains. -Zaragozic Acid A was extracted from an unidentified sterile fungal culture, Sporormiella intermedia, and Zaragozic Acid B and C from a fungal strain, Leptodontium elatius. -Class of Natural Products that have been shown to be potent inhibitor of both squalene synthase, an enzyme found in the cholestrol biosynthetic pathway, and farnesyl-protein transferase(FPTase), a potential target enzyme in the treatment of cancer. Sooty Blotch = Leptodontium elastius
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Family of Zaragozic Acids.Nicolaou (Dihydroxylation Strategy).Carreira (Carbonyladdition Strategy).Evans (Tartrate-Derived Aldol Strategy)
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Outline -Total Synthesis of Zaragozic Acid:.A: Nicolaou -Synthesis of the Side Chains.C. Carreira -Synthesis of the Side Chains.C: Evans
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Nicolaou’s Retrosynthesis Addition of the C6 O-Acyl Side Chain Addition of the C1 Akyl Side Chain Yue, E. W.; La Greca, S.; Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De Riccardis, F.; Nicolaou, K.C. Chem. Eur. J. 1995, 1, 467-494. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Nicolaou’s Retrosynthesis Dihydroxylation Stille Coupling Yue, E. W.; La Greca, S.; Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De Riccardis, F.; Nicolaou, K.C. Chem. Eur. J. 1995, 1, 467-494. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Synthesis of the C1 Akyl Side Chain Yue, E. W.; La Greca, S.; Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De Riccardis, F.; Nicolaou, K.C. Chem. Eur. J. 1995, 1, 467-494. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Synthesis of the C1 Akyl Side Chain Yue, E. W.; La Greca, S.; Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De Riccardis, F.; Nicolaou, K.C. Chem. Eur. J. 1995, 1, 467-494. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656. >95:5
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Synthesis of the C1 Akyl Side Chain Yue, E. W.; La Greca, S.; Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De Riccardis, F.; Nicolaou, K.C. Chem. Eur. J. 1995, 1, 467-494. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Synthesis of the C1 Akyl Side Chain Yue, E. W.; La Greca, S.; Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De Riccardis, F.; Nicolaou, K.C. Chem. Eur. J. 1995, 1, 467-494. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656. C1 Alkyl Side Chain 8% overall yield in 10 steps from 4 (allylic alcohol) Recrystallisation for cyclohexane to give 95% ee
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Synthesis of C6 O-Acyl Side Chain Yue, E. W.; La Greca, S.; Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De Riccardis, F.; Nicolaou, K.C. Chem. Eur. J. 1995, 1, 467-494. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656. C6 O-Acyl Side Chain 92% de
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Stille Coupling Organostannate R-Halide Yue, E. W.; La Greca, S.; Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De Riccardis, F.; Nicolaou, K.C. Chem. Eur. J. 1995, 1, 467-494. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Stille Coupling Yue, E. W.; La Greca, S.; Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De Riccardis, F.; Nicolaou, K.C. Chem. Eur. J. 1995, 1, 467-494. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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1 st Assymetric Dihydroxylation β-face α-face Yue, E. W.; La Greca, S.; Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De Riccardis, F.; Nicolaou, K.C. Chem. Eur. J. 1995, 1, 467-494. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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2 nd Assymetric Dihydroxylation Yue, E. W.; La Greca, S.; Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De Riccardis, F.; Nicolaou, K.C. Chem. Eur. J. 1995, 1, 467-494. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Functionalization Yue, E. W.; La Greca, S.; Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De Riccardis, F.; Nicolaou, K.C. Chem. Eur. J. 1995, 1, 467-494. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Functionalization Yue, E. W.; La Greca, S.; Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De Riccardis, F.; Nicolaou, K.C. Chem. Eur. J. 1995, 1, 467-494. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Dithiane Addition – 1 st Attempt Yue, E. W.; La Greca, S.; Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De Riccardis, F.; Nicolaou, K.C. Chem. Eur. J. 1995, 1, 467-494. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656. Undesired Product
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Dithiane Addition – 2 nd Attempt Yue, E. W.; La Greca, S.; Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De Riccardis, F.; Nicolaou, K.C. Chem. Eur. J. 1995, 1, 467-494. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Rearrangement Cascade Yue, E. W.; La Greca, S.; Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De Riccardis, F.; Nicolaou, K.C. Chem. Eur. J. 1995, 1, 467-494. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Dithiane Addition – 3 rd Attempt Yue, E. W.; La Greca, S.; Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De Riccardis, F.; Nicolaou, K.C. Chem. Eur. J. 1995, 1, 467-494. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Rearrangement Cascade Yue, E. W.; La Greca, S.; Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De Riccardis, F.; Nicolaou, K.C. Chem. Eur. J. 1995, 1, 467-494. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Coupling of the Side Chain Yue, E. W.; La Greca, S.; Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De Riccardis, F.; Nicolaou, K.C. Chem. Eur. J. 1995, 1, 467-494. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Completion of the Total Synthesis Yue, E. W.; La Greca, S.; Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De Riccardis, F.; Nicolaou, K.C. Chem. Eur. J. 1995, 1, 467-494. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656. Zaragozic Acid A
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Nicolaou’s Total Synthesis Summary Yue, E. W.; La Greca, S.; Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De Riccardis, F.; Nicolaou, K.C. Chem. Eur. J. 1995, 1, 467-494. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Carreira’s Retrosythesis Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1994, 116, 10825-10826., Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 8106-8125. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656. Addition of C6 side chain Ketalisation Addition of C1 side chain
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Synthesis of the C1 Akyl Side Chain Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1994, 116, 10825-10826., Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 8106-8125. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Synthesis of the C1 akyl chain C1 Akyl Chain Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1994, 116, 10825-10826., Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 8106-8125. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Synthesis of C6 O-Acyl Side Chain Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1994, 116, 10825-10826., Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 8106-8125. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656. >95% ee 60:40 mixture
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Synthesis of C6 O-Acyl Side Chain C6 O-Acyl Side Chain Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1994, 116, 10825-10826., Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 8106-8125. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Carbonyl Addition 20:1 Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1994, 116, 10825-10826., Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 8106-8125. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Addition of the C1 Alkyl Chain Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1994, 116, 10825-10826., Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 8106-8125. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Functionalization Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1994, 116, 10825-10826., Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 8106-8125. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Ketalizaton Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1994, 116, 10825-10826., Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 8106-8125. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Functionalization Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1994, 116, 10825-10826., Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 8106-8125. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Towards Zaragozic Acid C Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1994, 116, 10825-10826., Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 8106-8125. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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1 st Method Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1994, 116, 10825-10826., Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 8106-8125. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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1 st Method Cont’d Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1994, 116, 10825-10826., Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 8106-8125. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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1 st Method Cont’d Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1994, 116, 10825-10826., Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 8106-8125. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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2 nd Method Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1994, 116, 10825-10826., Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 8106-8125. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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2 nd Method Cont’d Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1994, 116, 10825-10826., Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 8106-8125. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Towards Zaragozic Acid C Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1994, 116, 10825-10826., Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 8106-8125. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1994, 116, 10825-10826., Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 8106-8125. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656. Addition of the C6 O-Acyl Side Chain (+)-Zaragozic Acid C If coupling of the C6 side chain was done on 50, the hydroxyl groups free at C6 and C7 position, a 1:3 mixture of C6:C7
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Carreira’s Total Synthesis Summary Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1994, 116, 10825-10826., Du Bois, J.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 8106-8125. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656. -Highly diastereoselective addition of the Grignard to an unsaturated ketone: + effect of Cosolvant and additive -Use of [Cr(OAc) 2.H 2 O] 2 for stereoselective reduction -Regiselective protection of the C7 carbinol vs the C6 OH -Installation of 3 aldehydes simultaneously (more efficient)
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Evans’s Retrosynthesis Esterification Ketalisation Addition Zaragozic Acid C Barrow, J. C.; Leighton, J. L.; Robichaud, A. J.; Sefkow, M.; Evans, D. A. J. Am. Chem. Soc. 1994, 116, 12111-12112. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Evans’s Retrosynthesis Mukaiyama Aldol Reaction Evan’s Aldol Reaction Barrow, J. C.; Leighton, J. L.; Robichaud, A. J.; Sefkow, M.; Evans, D. A. J. Am. Chem. Soc. 1994, 116, 12111-12112. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Evans Aldol Reaction Barrow, J. C.; Leighton, J. L.; Robichaud, A. J.; Sefkow, M.; Evans, D. A. J. Am. Chem. Soc. 1994, 116, 12111-12112. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Mukaiyama Aldol Reaction Barrow, J. C.; Leighton, J. L.; Robichaud, A. J.; Sefkow, M.; Evans, D. A. J. Am. Chem. Soc. 1994, 116, 12111-12112. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Functionalization Correct C5 Dia Barrow, J. C.; Leighton, J. L.; Robichaud, A. J.; Sefkow, M.; Evans, D. A. J. Am. Chem. Soc. 1994, 116, 12111-12112. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656. >10:1
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Functionalization Barrow, J. C.; Leighton, J. L.; Robichaud, A. J.; Sefkow, M.; Evans, D. A. J. Am. Chem. Soc. 1994, 116, 12111-12112. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Coupling of the Side Chain Barrow, J. C.; Leighton, J. L.; Robichaud, A. J.; Sefkow, M.; Evans, D. A. J. Am. Chem. Soc. 1994, 116, 12111-12112. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Completion of the Total Synthesis (+)-Zaragozic Acid C Barrow, J. C.; Leighton, J. L.; Robichaud, A. J.; Sefkow, M.; Evans, D. A. J. Am. Chem. Soc. 1994, 116, 12111-12112. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656.
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Evan’s Total Synthesis Summary Barrow, J. C.; Leighton, J. L.; Robichaud, A. J.; Sefkow, M.; Evans, D. A. J. Am. Chem. Soc. 1994, 116, 12111-12112. Koert, U. Angew. Chem. Int. Ed. Engli. 1995, 34, 773-778., Nadin, A.; Nicolaou, K.C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1622-1656. - Efficient Total Synthesis:.Convergent.Late coupling of the 2 side chains - Complete control exerted over each newly formed chiral center
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Total Synthesis Summary Carreira (Carbonyladdition Strategy) Nicolaou (Dihydroxylation Strategy) Evans (Tartrate-Derived Aldol Strategy)
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Retrosynthetic Analysis
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