Total synthesis of tubulysin U and N¹⁴-desacetoxytubulysin H

Abstract

<p>A concise and efficient procedure for the total synthesis of tubulysin U and N¹⁴-desacetoxytubulysin H has been developed with high stereoselectivity on a gram scale.</p>

Formal synthesis of cyclotheonellazole A

“…18 The desired thiazole 15 was successfully prepared in 75% yield through a cascade one-pot process under mild conditions by following the procedure of Du et al with modifications. 19 The potential of this method was also demonstrated through the total synthesis of linear tetrapeptides tubulysin U and N 14 -desacetoxytubulysin H 16 previously reported by our group.…”

“…In addition, total synthesis provides materials for biological testing towards pharmaceutical development. Although the total synthesis of CA has recently been reported, 11 considering our previous work on the synthesis of marine peptides [12][13][14][15][16] and particularly those containing thiazole, 16 the unique structure and extremely potent protease inhibitor activities of CA have received much attention as an attractive target for total synthesis.…”

Applications of ultrasound in total synthesis of bioactive natural products: A promising green tool

“…The tubulysins, the most potent anticancer molecules ever discovered from Nature [144] , [145] , [146] , are a family of architecturally complex tetrapeptides which were isolated from the myxobacteria Archangium gephyra and Angiococus disciformis [147] . Tubulysins are structurally linked to the marine natural product; the complex molecular architecture of it contains four uncommon amino acid fragments, N -methylpipecolic acid (Mep), isoleucine (Ile), tubuvaline (Tuv), and tubuphenylalanine (Tup) or Tubutyrosine (Tut) [148] . Biologically, they show potent cytotoxic activities and many members of this family surpass the well-known chemotherapeutic agents such as taxol, epothilones, and vinblastine by a factor of 20–1000 concerning growth inhibition potential [149] .…”