Hyogo University of

Norcembranolide diterpenes, isolated from the soft corals of the genus Sinularia, are important compounds for the development of new drugs, owing to their diverse biological activities. However, total synthesis methods for these compounds are scarce. Now, a team of researchers has achieved the total synthesis of scabrolide F, a norcembranolide diterpene. They also revealed its non-toxic antifouling properties. This novel method can lead to the development of new drugs and antifouling agents. Marine organisms produce many organic compounds with diverse chemical structures and biological activities. These natural marine products are regarded as potential starting points for the discovery and development of new drugs. Among these are norcembranolide diterpenes isolated from the soft corals of the genus Sinularia. These compounds exhibit diverse biological activities, and many of them have anti-cancer and anti-inflammatory properties. Consequently, many studies have investigated the properties of norcembranolide diterpenes and their synthesis methods. Given their potential in drug discovery, developing a synthetic method to produce these compounds is essential. However, reports on the total synthesis of norcembranolide diterpenes are limited. In a recent study, a team of researchers from Japan led by Associate Professor Hiroyoshi Takamura and including Yuki Sugitani, Ryohei Morishita, and Isao Kadota, all from the Department of Chemistry, Graduate School of Natural Science and Technology at Okayama University, achieved the total synthesis of a norcembranolide diterpene. "In this research, we succeeded in the chemical synthesis of scabrolide F, a natural product that was isolated from a soft coral Sinularia scabra. Moreover, we found that synthetic scabrolide F and its related compounds exhibited antifouling activity without toxicity, which can potentially prevent the damage caused by biofouling, namely, the accumulation of microorganisms, plants, and algae," explains Dr. Takamura. The study, published in the journal Organic & Biomolecular Chemistry on May 23, 2024, included contributions from Takefumi Yorisue from the Institute of Natural and Environmental Sciences, University of Hyogo, as well as the Division of Nature and Environmental Management, Museum of Nature and Human Activities. To synthesize scabrolide F, the researchers designed a hydrocarboxylic acid compound as the key intermediate. They initially attempted to synthesize the intermediate through the coupling of the tetrahydrofuran and the dithiane fragments. The coupling product could then be transformed into the intermediate through an allylation reaction. However, their model study for testing the allylation reaction failed to yield the desired product, prompting the team to pursue an alternative method. In the second approach, they successfully fabricated the intermediate through a reaction called fragment coupling between an alkyl iodide and an aldehyde. The intermediate was then transformed to the desired scabrolide F, through two key transformations, namely, macrolactonization, which refers to the intramolecular reaction between the hydroxyl group and carboxylic group of the intermediate, and transannular ring-closing metathesis, which forms a ring within an existing macrocyclic ring. This innovative method represents the total synthesis of scabrolide F. Furthermore, the researchers evaluated the antifouling activity and toxicity of this compound and its five key synthetic intermediates against the cypris larvae of the barnacle Amphibalanus amphitrite. All six compounds were found to have antifouling activity with 50% effective concentration or EC50 values ranging from 2.65-9.46 μg/mL and were non-toxic with 50% lethal concentration or LC50 toxicity level greater than 50 μg/mL. Additionally, one of the intermediates was identified as suitable for the preparation of non-toxic antifouling agents. The synthesis method present in the study will also be useful for the synthesis of other norcembranolide diterpenes. Highlighting the practical applications of the study, Dr. Takamura says "Preventing damage caused by biofouling is a key global issue. It is expected that organic compounds synthesized in this research can be used to create new antifouling agents and paints." Overall, the strategy for the total synthesis of norcembranolide diterpenes proposed in this study can aid in the development of antifouling agents and the discovery of new drugs.

Scientists have investigated lamprey embryos using cutting-edge microscopic techniques to reveal interesting insights about vertebrate head evolution, clarifying an unresolved mystery in basic science. Since the 18th century, several theories regarding the origin of the vertebrate head have been proposed. However, owing to the lack of molecular and morphological studies, the question of whether the vertebrate head evolved as a modified embryonic segment or originated as an independent unsegmented head remains unanswered. Now, scientists from Japan have investigated lamprey embryos using cutting-edge microscopic techniques to reveal interesting insights about vertebrate head evolution, clarifying an unresolved mystery in basic science. The origin of the vertebrate skull is a topic of much debate among evolutionary biologists. Some believe that the vertebrate head has developed as a result of modification of the segmental elements of the trunk, such as the vertebrae and somites. On the other hand, others believe that the vertebrate head has evolved as a new, unsegment body part, unrelated to other widely observed embryonic segments somites. Interestingly, previous studies on embryos have revealed the presence of some vestiges of somites in the head mesoderm (e.g., head cavities and somitomeres). However, homology between trunk somites and such head segments has been controversial. The failure to understand the evolutionary origins of the vertebrate head is also attributable to the lack of studies on extant species such as lampreys, which are known to share several traits with fossil jawless vertebrates and retain primitive traits related to the head mesoderm. While some studies have focused on the embryonic morphology of lampreys, they have often fallen short because of challenges like tissue destruction and acidic fixation during examination, making it difficult to observe the formation of head mesoderm and trunk somites. Now, however, a research team led by Assistant Professor Takayuki Onai from the University of Fukui, Japan, has utilized advanced techniques like transmission electron microscopy and serial block-face scanning electron microscopy (SBF-SEM) to understand the development of the head mesoderm and somites in lamprey embryos. The researchers also analyzed the morphology and gene expression patterns of cephalochordate and hemichordate (both being invertebrates) to understand the origins of somites and head mesoderm from an evolutionary perspective. This paper was made available online in iScience on November 13, 2023, and is co-authored by Dr. Noritaka Adachi from Aix-Marseille Université, Dr. Hidetoshi Urakubo from the National Institute for Physiological Sciences (NIPS), Dr. Fumiaki Sugahara from Hyogo Medical University, Dr. Toshihiro Aramaki from Osaka University, Dr. Mami Matsumoto from NIPS and Nagoya City University, and Dr. Nobuhiko Ohno from NIPS and Jichi Medical University. To clarify the presence or absence of somites in the head mesoderm during early stages of diversification, the researchers focused on rosettes, which are major somite patterns and are important for the subsequent development of vertebrae. Their initial observations of lamprey embryos showed that the tissue closely related to the formation of facial muscles and other elements of the skull, known as the head mesoderm, did have cell clusters with features similar to somite rosettes. To clarify if these cell clusters were indeed rosettes, they conducted ultrastructural experiments, including the SBF-SEM and gene expression analysis. This examination of the cellular morphology and gene expression revealed that the cell clusters were clearly distinct from rosettes. "The cell clusters we observed are likely lamprey-specific features, as they are not recognizable in the head mesoderm of both hagfish and shark embryos," explains Dr. Onai. Furthermore, gene expression analysis also revealed the absence of segmental expression of somitogenesis-related genes, indicating their distinctiveness from somites. These findings indicate that the rosette pattern typically seen in somites is not necessarily the essential or most basic feature that defines the process of bodily segmentation. Moreover, the experiments provide evidence that the vertebrate head mesoderm diverged during the early phases of vertebrate evolution. Furthermore, comparison of embryos of hemichordates (a basal deuterostome), amphioxus (a basal chordate), and vertebrates revealed that the somites likely arose from the "endomesoderm" tissue of an ancient deuterostome ancestor. The evolutionary origin of somites has been the central question in zoology for more than 150 years, and in this study, Onai et al., revealed the enigma. Regarding the evolutionary mechanism for the emergence of head mesoderm, they found that the head mesoderm emerged upon the segregation of mesodermal genes between the front and back parts (rostro-caudal axis) of organisms. "Taken together, our findings revealed a different evolutionary origin for the vertebrate head mesoderm, suggesting that it evolved from the repatterning of an ancient mesoderm and diversified even before the emergence of jawed vertebrates," concludes Dr. Onai. In summary, the finding that the cell clusters present in the head mesoderm are distinct morphologically and molecularly from somites, favors a new model where the vertebrate head mesoderm diverged during early evolution. This sheds more light on the age-old debate on the evolution of the vertebrate head and can help us advance the understanding of our own origins.

Scientists investigating a compound called 'Y-ball' -- which belongs to a mysterious class of 'strange metals' viewed as centrally important to next-generation quantum materials -- have found new ways to probe and understand its behavior. Scientists investigating a compound called "Y-ball" - which belongs to a mysterious class of "strange metals" viewed as centrally important to next-generation quantum materials - have found new ways to probe and understand its behavior. The results of the experiments, aided by the insights of theoretical physicists at Rutgers, could play a role in the development of revolutionary technologies and devices. "It's likely that that quantum materials will drive the next generation of technology and that strange metals will be part of that story," said Piers Coleman, a Distinguished Professor at the Rutgers Center for Materials Theory in the Department of Physics and Astronomy at the Rutgers School of Arts and Sciences and one of the theoreticians involved in the study. "We know that strange metals like Y-ball exhibit properties that need to be understood to develop these future applications. We're pretty sure that understanding this strange metal will give us new ideas and will help us design and discover new materials." Reporting in the journal Science, an international team of researchers from Rutgers, the University of Hyogo and the University of Tokyo in Japan, the University of Cincinnati and Johns Hopkins University described details of electron motion that provide new insight into the unusual electrical properties of Y-ball. The material, technically known as the compound YbAlB4, contains the elements ytterbium, aluminum and boron. It was nicknamed "Y-ball" by the late Elihu Abrahams, founding director of the Rutgers Center for Materials Theory. The experiment revealed unusual fluctuations in the strange metal's electrical charge. The work is groundbreaking, the researchers said, because of the novel way the experimenters examined Y-ball, firing gamma rays at it using a synchrotron, a type of particle accelerator. The Rutgers team -- including Coleman, fellow physics professor Premala Chandra and former postdoctoral fellow Yashar Komijani (now an assistant professor at the University of Cincinnati) -- have spent years exploring the mysteries of strange metals. They do so through the framework of quantum mechanics, the physical laws governing the realm of the ultra-small, home of the building blocks of nature such as electrons. Analyzing the material using a technique known as Mossbauer spectroscopy, the scientists probed Y-ball with gamma rays, measuring the rate at which the strange metal's electrical charge fluctuates. In a conventional metal, as they move, electrons hop in and out of the atoms, causing their electrical charge to fluctuate, but at a rate that is thousands of times too fast to be seen by Mossbauer spectroscopy. In this case, the change happened in a nanosecond, a billionth of a second. "In the quantum world, a nanosecond is an eternity," said Komijani. "For a long time, we have been wondering why these fluctuations are actually so slow." "We reasoned," continued Chandra, "that each time an electron hops into an ytterbium atom, it stays there long enough to attract the surrounding atoms, causing them to move in and out. This synchronized dance of the electrons and atoms slows the whole process so that it can be seen by the Mossbauer." They moved to the next step. "We asked the experimentalists to look for these vibrations," said Komijani, "and to our delight, they detected them." Coleman explained that when an electrical current flows through conventional metals, such as copper, random atomic motion scatters the electrons causing friction called resistance. As the temperature is raised, the resistance increases in a complex fashion and at some point it reaches a plateau. In strange metals such as Y-ball, however, resistance increases linearly with temperature, a much simpler behavior. In addition, further contributing to their "strangeness," when Y-ball and other strange metals are cooled to low temperatures, they often become superconductors, exhibiting no resistance at all. The materials with the highest superconducting temperatures fall into this strange family. These metals are thus very important because they provide the canvas for new forms of electronic matter -- especially exotic and high temperature superconductivity. Superconducting materials are expected to be central to the next generation of quantum technologies because, in eliminating all electrical resistance, they allow an electric current to flow in a quantum mechanically synchronized fashion. The researchers see their work as opening a door to future, perhaps unimaginable possibilities. "In the 19th century, when people were trying to figure out electricity and magnetism, they couldn't have imagined the next century, which was entirely driven by that understanding," Coleman said. "And so, it's also true today, that when we use the vague phrase 'quantum materials,' we can't really envisage how it will transform the lives of our grandchildren."