Total synthesis and biological evaluation of spirotryprostatin A analogs

Abstract

Based on the spirotryprostatin A structure, a series of compounds belonging to spiro-indolyl diketopiperazine structural class were designed and synthesized, which embody an oxindole with an all-carbon quaternary stereocenter. The total synthesis can efficiently be accessed in a seven-step reaction sequence with 18-28% overall yield from commercially available materials, and a highly enantioselective 1,3-dipolar cycloaddition, N-acylation of the resulting stereochemically complex spiro[pyrrolidin-3,3'-oxindole]s core with Fmoc-L-pro-Cl and spontaneous ring closure upon N-deprotection were obtained. The synthesized compounds 13a-e and 15a-e were evaluated for their antibacterial activities. The result showed that compounds 13b and 15b were active only against Gram-positive bacteria, and selective antibacterial activity was exhibited by compounds 13d and 13e against Streptococcus lactis. Further, all the remaining compounds showed a certain degree of antibacterial activity. In addition, the structure-activity relationship is also discussed.

Synthesis, Antimicrobial Activity, Structure-Activity Relationship, and Molecular Docking Studies of Indole Diketopiperazine Alkaloids

“…In consideration of this failure, we turned our attention to developing another approach for the preparation of the spiro-pentacyclic scaffold via a 1,3-dipolar cycloaddition of N -unprotected 2-oxoindolin-3-ylidenes and azomethine ylides, followed by the above synthetic routes. Finally, spiro-pentacyclic compounds 5a−5e were obtained successfully, as shown in Scheme 3 (Ma et al, 2017).…”

“…The synthetic routes of indole DKPs 2a−2f , 3a−3d , 4a−4d , and 5a−5e are outlined in Scheme 2 and 3. General procedure for the synthesis of these compounds have been described in our previous research (Ma et al, 2013, 2014, 2017).…”

Spiro‐2‐oxindoles via 1,3‐dipolar cycloadditions. A decade update

“…Other approaches to spirotryprostatin A were provided by asymmetric azomethine ylide cycloadditions catalysed by silver(I) acetate [72,73] in the presence of triethylamine and the organic ligand ( S )‐TF‐BiphamPhos 26 (5 mol%). The reactions occurred at r.t. in 3–5 h. Cycloadduct structures and the proposed reactive complexes are depicted in Figure 4.…”

Design, Synthesis, Antifungal Evaluation, Structure–Activity Relationship (SAR) Study, and Molecular Docking of Novel Spirotryprostatin A Derivatives

“…Therefore, developing efficient and practical methodologies for synthesizing spirotryprostatin A scaffolds and observing their fungicidal activity are significant objectives. It is worth noting that our group was the first to discover the fungicidal activity of spirotryprostatin A derivatives [ 13 ]. However, the limited number of available compounds for managing fungal diseases means that developing effective and safe fungicides is a complex process that requires extensive research.…”