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Volumn 46, Issue 7, 2007, Pages 1066-1070

The total synthesis of the oxopolyene macrolide RK-397

Author keywords

Asymmetric synthesis; Macrocycles; Macrolides; Metathesis; Total synthesis

Indexed keywords

ALCOHOLS; CHAIN LENGTH; OLEFINS; REACTION KINETICS; SYNTHESIS (CHEMICAL);

EID: 34247264848     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.200602601     Document Type: Article
Times cited : (63)

References (44)
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    • For partial syntheses of RK-397, see: a S. A. Burova, F. E. McDonald, J. Am. Chem. Soc. 2002, 124, 8188-8189;
    • For partial syntheses of RK-397, see: a) S. A. Burova, F. E. McDonald, J. Am. Chem. Soc. 2002, 124, 8188-8189;
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    • For related macrolactonization approaches to oxopolyene macrolides, see: a
    • For related macrolactonization approaches to oxopolyene macrolides, see: a) Y. Mori, M. Asai, J-i. Kawade, A. Okumura, H. Furukawa, Tetrahedron Lett. 1994, 35, 6503-6506;
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    • for syntheses utilizing these methods, see: c
    • for syntheses utilizing these methods, see: c) Ref. [9b];
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    • Ref, 8];
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    • 3N, see Ref. [10a]) on similar substrates provided lower selectivity (<2:1).
    • 3N, see Ref. [10a]) on similar substrates provided lower selectivity (<2:1).
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    • K. M. Chen, G. E. Hardtmann, K. Prasad, O. Repic, M. J. Shapiro, Tetrahedron Lett. 1987, 28, 155-158. Reduction of hydroxyenone 11 using conditions reported in the reference above (Et 2BOMe, NaBH4) gave the 1,3-syn diol as a single diastereomer on a small scale. On larger scales, this transformation was accompanied by partial cleavage of the C23 and C31 protecting groups during workup. Fortunately, both of these groups must be removed in the next step to give our desired C22-C33 ketone intermediate 2. In practice, treatment of the mixture of partially deprotected compounds with FeCl3 in dry acetone containing desispheres resulted in complete desilylation, benzodioxepine removal, and acetonide installation to afford 2 in good yield 68, 2 steps
    • 3 in dry acetone containing desispheres resulted in complete desilylation, benzodioxepine removal, and acetonide installation to afford 2 in good yield (68%, 2 steps).
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    • Compound 13 is prone to hydration and polymerization. We have found this polymerization to be reversible and that the bisaldehyde can be obtained by dehydration see the Supporting Information for details, For a similar observation and transformation, reported while this work was in progress, see: J. N. Shepherd, D. C. Myles, Org. Lett. 2003, 5, 1027-1030
    • Compound 13 is prone to hydration and polymerization. We have found this polymerization to be reversible and that the bisaldehyde can be obtained by dehydration (see the Supporting Information for details). For a similar observation and transformation, reported while this work was in progress, see: J. N. Shepherd, D. C. Myles, Org. Lett. 2003, 5, 1027-1030.
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    • For other reagent-controlled asymmetric allylations and crotylations, see:, and references therein
    • For other reagent-controlled asymmetric allylations and crotylations, see: C. H. Burgos, E. Canales, K. Matos, J. A. Soderquist, J. Am. Chem. Soc. 2005, 127, 8044-8049, and references therein.
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    • See Ref. [10a]. In this case, the Paterson conditions proved superior to the Evans conditions because of a greater preference for enolization at C22.
    • See Ref. [10a]. In this case, the Paterson conditions proved superior to the Evans conditions because of a greater preference for enolization at C22.
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    • Ed, R. H. Grubbs Wiley-VCH, Weinheim
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    • This material was purified by reverse-phase HPLC to provide a sample for characterization see the Supporting Information for details
    • This material was purified by reverse-phase HPLC to provide a sample for characterization (see the Supporting Information for details).


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