Heronamides are biosynthetically related metabolites isolated from marine-derived actinomycetes. Heronamide C shows potent antifungal activity by targeting membrane phospholipids possessing saturated hydrocarbon chains with as-yet-unrevealed modes of action. In spite of their curious hypothesized biosynthesis and fascinating biological activities, there have been conflicts in regard to the reported stereochemistries of heronamides. Here, we describe the asymmetric total synthesis of the originally proposed and revised structures of heronamide C, which unambiguously confirmed the chemical structure of this molecule. We also demonstrated nonenzymatic synthesis of heronamides A and B from heronamide C, which not only proved the postulated biosynthesis, but also confirmed the correct structures of heronamides A and B. Investigation of the structure-activity relationship of synthetic and natural heronamides revealed the importance of both long-range stereochemical communication and the 20-membered macrolactam ring for the biological activity of these compounds.

The total synthesis of the proposed structure of heronamide C was accomplished through a Sato–Micalizio reductive alkyne–alkyne coupling strategy and remote‐amine controlled stannylcupration. However, the physical data for the synthetic and natural samples differ from each other, which suggests that the proposed structure should be reinvestigated.

These results affirm the importance of the ipsilateral masseter muscle and quantitatively demonstrate the important contribution of the ipsilateral medial pterygoid and contralateral lateral pterygoid muscles during unilateral mastication.

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.

The primary mechanosensitive neurons innervating the temporomandibular joint (TMJ neurons) may play an important role in controlling mandibular movement and position. The purpose of the study was to investigate the neurophysiological properties of TMJ neurons during passive movement of the isolated condyle in 55 rabbits and the intact condyle in 29 rabbits. Discharges of TMJ neurons from the trigeminal ganglion were recorded with a microelectrode as the isolated condyle was moved manually and by a computer-regulated mechanostimulator and as the intact condyle was manually stimulated. A total of 237 TMJ neurons were recorded rostrocaudally from the mandibular nerve area lateral to the maxillary region in the dorsal half of the trigeminal ganglion. Of the recorded TMJ units, 97% were slowly adapting (SA) and 67% of the SA units had an accompanying ongoing discharge. The proportion of adaptation types and appearance of ongoing discharges for the isolated condyle did not differ significantly from those for the intact condyle. Most of the TMJ units (89%) responded multidirectionally to the rostral and ventral movements of the isolated condyle. The discharge frequencies of the TMJ units increased as the condylar displacement and velocity increased within a 5-mm anterior displacement of the isolated condyle. Displacement of the isolated condyle influenced the discharge frequency of the units to a greater extent than the velocity of the condyle movement. No responses of TMJ units were observed during the descending ramp. Based on these results, we conclude that sensory information is transmitted by TMJ neurons encoding joint position, displacement and velocity in a physiological range of mandibular displacement.