The total synthesis of (+ +)-neooxazolomycin was achieved from the amino-acid d-serine.T he efficiency of this approach is derived from the use of principles of memory of chirality and dynamic kinetic resolution in the intramolecular aldol reaction of as erine derivative to build the densely functionalizedl actam framework and to install three contiguous stereocenters.T he key intermediate was readily elaborated to the target natural product.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Persistently activated STAT3 is a promising target for a new class of anticancer drug development and cancer therapy, as it is associated with tumor initiation, progression, malignancy, drug resistance, cancer stem cell properties, and recurrence. Here, we discovered 3-(2,4-dichloro-phenoxymethyl)-5-trichloromethyl-[1,2,4]oxadiazole (ODZ10117) as a small-molecule inhibitor of STAT3 to be used in STAT3-targeted cancer therapy. ODZ10117 targeted the SH2 domain of STAT3 regardless of other STAT family proteins and upstream regulators of STAT3, leading to inhibition of the tyrosine phosphorylation, dimerization, nuclear translocation, and transcriptional activity of STAT3. The inhibitory effect of ODZ10117 on STAT3 was stronger than the known STAT3 inhibitors such as S3I-201, STA-21, and nifuroxazide. ODZ10117 suppressed the migration and invasion, induced apoptosis, reduced tumor growth and lung metastasis, and extended the survival rate in both in vitro and in vivo models of breast cancer. Overall, we demonstrated that ODZ10117 is a novel STAT3 inhibitor and may be a promising agent for the development of anticancer drugs.

Herein, we report the asymmetric total syntheses of inthomycin antibiotics containing a methylene-interrupted oxazolyl-triene motif. Utilizing the α,β-unsaturated aldehyde as a common intermediate, all three inthomycins A−C were divergently synthesized. The asymmetric ynone reduction provided an R-configured secondary alcohol as in the natural products with high enantioselectivity. The geometrically different triene units for each inthomycin were stereoselectively established via methyl cuprate conjugate addition, isomerization of the α,β-unsaturated aldehyde intermediate, and stereoretentive cross-coupling reactions.

The total synthesis of (+ +)-neooxazolomycin was achieved from the amino-acid d-serine.T he efficiency of this approach is derived from the use of principles of memory of chirality and dynamic kinetic resolution in the intramolecular aldol reaction of as erine derivative to build the densely functionalizedl actam framework and to install three contiguous stereocenters.T he key intermediate was readily elaborated to the target natural product.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

A one pot, three‐step cascade reaction to provide functionalized proline derivatives was developed. The Michael addition reaction of N‐allylated proline and activated alkyne forms a zwitterionic intermediate that further undergoes cyclization and [2,3]‐rearrangement to provide Cα‐alkylated proline bicyclic derivatives. This transformation was highly stereoselective and the chirality of the N‐allylated prolines was completely transferred to the product via a C−N−C chirality transfer process. The developed reaction is operationally simple and does not require any reagents other than the substrates.magnified image