Improved total synthesis of incednam

Abstract

An alternative and improved total synthesis of incednam, the aglycon of the 24-membered macrolactam glycoside antibiotic incednine, was accomplished. The synthesis was realized via construction of the 24-membered macrocycle using intramolecular ring-closing olefin metathesis reaction as a key step.

Stereodivergent Diversity‐Oriented Synthesis: Exploiting the Versatility of 2‐Piperidine Ethanol

“…With compounds 3a-d in our hands, a Mitsunobu reaction in the presence of diphenylphosphoryl azide (DPPA) was performed, [18] followed by a Staudinger reduction of the obtained azide. [19] In this way, the interconversion of compounds 3a-d into the corresponding amines (4a-d) was achieved with inversion of configuration. The amines were treated with acryloyl chloride (5a-d), affording the amides, which were converted into lactams (6a-d) through a ring-closing metathesis (RCM).…”

Asymmetric Total Synthesis of Heronamides A–C: Stereochemical Confirmation and Impact of Long‐Range Stereochemical Communication on the Biological Activity

“…In previous studies, we and others successfully utilized ring‐closing metathesis (RCM) reactions during the total synthesis of polyene macrocyclic natural products such as vicenistatin, FD‐891, and incednam . We therefore attempted to construct a 20‐membered polyene macrolactam skeleton by using RCM as shown in Scheme .…”

“…In previouss tudies, we and others successfully utilized ringclosing metathesis (RCM) reactions during the total synthesis of polyene macrocyclic naturalp roducts such as vicenistatin, [21] FD-891, [22] and incednam. [23] We therefore attempted to construct a2 0-membered polyenem acrolactams keleton by using RCM as shown in Scheme 6. The retrosynthetic disconnection between C10-C11 was chosen because 1) the RCM precursor would be easily accessible from our synthetic intermediate, and 2) we expected that C9-oxygen functionality of intermediate F could be used to modulate the reactivity of the vinyl group at C10, [24] which was sequesteredi nt he intramolecular pinacolcoupling reaction(see above).…”

Nitro and Other Electron Withdrawing Group Activated Ruthenium Catalysts for Olefin Metathesis Reactions

“…Theg roup from Keio University reported an improved total synthesis of incednam (2), the aglycon of the 24membered macrolactam glycoside antibiotic Incednine. [43] Theretrosynthetic analysis of 2 was based on the construction of the 24-membered macrocycle by ac hallenging intramolecular macrocyclization of the fragile polyunsaturated substrate 1 (Scheme 3). Conditions for the RCM were rigorously explored, such as screening of anumber of catalysts,including first-and second-generation Grubbs and Hoveyda-Grubbs catalysts,a sw ell as nitro catalyst Ru12.T hese tests revealed that the best conditions consist of using Ru12 in the presence of p-methoxyphenol (PMP) [44] and 3 molecular sieves.…”