Macrocyclic cytochalasans synthesis

Thomas E. J. Cytochalasan Synthesis Macrocycle Formation Via Intramolecular Diels-Alder Reactions Acc. Chem. Res. 1991 24 229 235... 

Thomas, EJ (1991) Cytochalasan Synthesis Macrocycle Formation vm Intramolecular Alder Reactions. Acc Chem Res 24 229... 

Finally, a thia Diels-Alder reaction representing a less common cycloaddition type in natural product synthesis shall be discussed. Thus, Vedejs et al. have included such a cycloaddition into an elegant strategy aimed at the synthesis of macrocyclic [ll]-cytochalasans such as zygosporin E 7-76 [536-538]. Thus, release of the thioaldehyde 7-73 from its phenacyl sulfide precursor in the presence of the silyloxydiene 7-74 yielded 7-75 as 2 1 mixture with its C20 epimer. Fortunately, equilibration of this mixture raised the ratio up to 10 1. Several subsequent steps yielded the tetracyclic intermediate 7-77 cleavage of its thioether moiety then liberated the 11-membered macrocycle present e.g. in zygosporin E 7-76 (Fig. 7-16). 

Intramolecular Diels-Alder reaction can be used as a macrocyclization means. Thomas and Whitehead [167] apphed this approach to the synthesis of the 13-membered cytochalasan proxiphomin (280). As shown in Scheme 94, the long chain precursor 278 was heated in toluene at 100 °C for 5 h to give the 13-membered skeleton 279 and the endo adduct (52 48) in 52% yield. There are several other examples of the application of intramolecular Diels-Alder reaction to the synthesis of macrocyclic natural products [168]. 

Cytochalasin B (1088) belongs to the [14]cytochalasan group and was isolated from Helminthosporium dematioideum (696) and Phoma S298 (695). Its first total synthesis was accomplished by Stork et al. in 1978 (740). Later, this group published a more simplified synthesis, utilizing an intramolecular Diels-Alder reaction as the key step, forming both perhydroisoindolone and the macrocyclic moiety in a single reaction (741). 

In 2004, Myers and Haidle reported a convergent and modular total synthesis of cytochalasin B (1088) and the [lljcytochalasan L-696,474 (1139) (742), using a late-stage macrocyclization step involving an intramolecular Horner-Wadsworth-Emmons olefination. Their strategy is applicable for the synthesis of cytochalasans of different ring sizes, as exemplified by these two total syntheses. Both macrolactone and macrocarbocyclic cytochalasans can lead back retrosyntheticaUy to the same precursors. The synthesis of the tricyclic isoindolone precursor to cytochalasin B (1088) and L-696,474 (1139) is shown in Scheme 14.1. 

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See also in sourсe #XX -- [ , , , , , ]

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