Trapoxin synthesized

Identification of Molecular Target From a comparison with chlamydocin (3), Taunton et al. speculated that the benzyl side chain was not required for detransformation activity, and synthesized a bioactive trapoxin-Uke molecule, K-trap... 

Trichostatin A (35) is structurally related to suberoylanilide hydroxamic acid (SAHA), a molecule that has reached the market as a therapy for the treatment of cutaneous T-cell lymphoma (CTCL), marketed as vorinostat. ° Hybrid derivatives have been synthesized combining features of trichostatin A and fungal-derived cyclic tetrapeptides such as trapoxin and apicidin, which show subnanomolar activities/ ... 

The synthesis of 3,4-0-isopropylidene-L- and -o-erythrulose from L-ascorbic-and D-isoascorbic acids, respectively, proceeding through the corresponding protected tetritols, is covered in Chapter 2. The syntheses of natural and modified trapoxins and (+)-lanomycin by way of suitably protected tetritol derivatives, and... 

The potent biological activity of the cyclic tetrapeptides coupled with their unusual structures has sparked extensive synthetic investigation into these compounds to establish SAR and identify analogues with improved biological profiles. Typically, these syntheses are carried out in solution-phase as in Schreiber s approach to trapoxin (Scheme 4.1). An exception is the total synthesis of microsporin A by Silverman using a solid-phase approach (Scheme 4.2). The Kenner safety-catch sulfonamide resin was used to assemble the linear tetrapeptide 17, followed by resin activation towards nucleophilic attack by alleviation of the sulfonamide with iodoacetonitrile. Boc deprotection of the N-terminus then induced macrocyclization to cleave the natural product from the resin. 

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