ChemInform Abstract: Total Synthesis of the Proposed Structure of Heronamide C.

Abstract

Total Synthesis of the Proposed Structure of Heronamide C. -Based on the physical data of the target compound a reinvestigation of the proposed structure of Heronamide C is suggested. -(SAKANISHI, K.; ITOH, S.; SUGIYAMA, R.; NISHIMURA, S.; KAKEYA, H.; IWABUCHI, Y.; KANOH*, N.; Eur. J. Org. Chem. 2014, 7, 1376-1380, http://dx.

Toward the Creation of Induced Pluripotent Small (iPS) Molecules: Establishment of a Modular Synthetic Strategy for the Heronamide C-type Polyene Macrolactams and Their Conformational and Reactivity Analysis

“…To synthesize the originally proposed structure 3 (Figure 1b), intermolecular Stille coupling between C11 iodide and C12 tributylstannane was first chosen as a key reaction (Figure 2a). However, the reaction gave the coupling product only in 8% yield 29 and the resulting unstable nonaene intermediate could not be used further. On the other hand, its intramolecular version, i.e., intramolecular Stille coupling, worked to give the corresponding macrocycle in 48% yield (Figure 2b), which could be used for the total synthesis of 3.…”

“…On the other hand, its intramolecular version, i.e., intramolecular Stille coupling, worked to give the corresponding macrocycle in 48% yield (Figure 2b), which could be used for the total synthesis of 3. 29 Unfortunately, the same strategy did not work for the substrate designed for the total synthesis of 1 (Figure 2c). 25 After many attempts, a ring-closing metathesis strategy using diacetate substrate was found to be effective in 11% but reproduceable yield (Figure 2d), culminating in the total synthesis of 1.…”

“…As described earlier, we previously had to adopt different strategies for the synthesis of different macrocyclic structures (Figure 2), 25,29 presumably because the macrocycles take different stable conformations depending on the substitution pattern and/or relative stereochemistry of substituents. Thus, the next question is whether the developed strategy described herein could be applied to the synthesis of macrolactams having different substitution patterns.…”

“…11 Moreover, 1 and 8-deoxyheronamide C (2), a biogenetic precursor of heronamides A-C, have been shown to bind to lipid membranes made up of phospholipids with saturated hydrocarbon chains and to exhibit growth inhibition against fission yeast with an asyet-unrevealed mode of action. Intrigued by the chemistry and biological activity of heronamides, we have been undertaking 3) 29 (Figure 1b), structure revision of heronamide C, and the synthesis of the revised structure of heronamide C (1). 25 However, to synthesize each of these structures, we had to develop different tactics, as shown in Figure 2 and discussed in detail later.…”

“…25 However, to synthesize each of these structures, we had to develop different tactics, as shown in Figure 2 and discussed in detail later. Moreover, our previous synthetic strategies to the polyene fragments relied on classical Wittig-type homologation sequences 29 and Ti-mediated alkyne-alkyne coupling, 25 which has low functional group compatibility, so that we were forced to take longer synthetic steps. Therefore, we decided to develop general synthetic tactics to synthesize not only natural products and molecular probes for the mode-of-action analysis, but also heronamide-like "induced pluripotent small" (iPS) molecules, that were named after iPS cells 30 and would differentiate into diverse molecular entities having different biological activity in response to external stimuli, such as heat and light, as heronamide C (1) does.…”