Masaru Enomoto

Lupinacidin C, an Inhibitor of Tumor Cell Invasion from Micromonospora lupini

A new anthraquinone derivative, lupinacidin C (1), was isolated from the endophytic actinomycete Micromonospora lupini. The structure was elucidated on the basis of spectroscopic analyses, and the absolute configuration was determined by total synthesis. Lupinacidin C (1) exhibited the most potent inhibitory effects among the congeners on the invasion of murine colon carcinoma cells into the reconstituted basement membrane.

Enantioselective Syntheses of Pachastrissamine and Jaspine A via Hydroxylactonization of a Chiral Epoxy Ester

A new enantioselective total synthesis of pachastrissamine (jaspine B) was achieved from a known α,β-unsaturated aldehyde by utilizing Córdova’s asymmetric epoxidation as the chirality-inducing step. The 2,3-cis stereochemistry of pachastrissamine was established via intramolecular epoxide ring opening of a γ,δ-epoxy-α,β-unsaturated ester intermediate coupled with oxy-Michael cyclization. Treatment of pachastrissamine with tetrahydro-2-furanol under acidic conditions led to smooth oxazolidine ring formation, furnishing jaspine A in a high yield.

Total Synthesis of the Tremorgenic Indole Diterpene Paspalinine

other indole diterpenoids, paspalinine (1), which bears a hydroxy group at the C13 position, exhibits mammal toxicity and often causes tremorgenic neurological disorders called “paspalum staggers” in domestic animals when they graze the pasture grass Paspalum dilatatum infected with C. paspali ; however, its congener 2, which lacks the hydroxy function, induces no such symptoms. In addition to tremorgenicity, this family of natural products has a variety of intriguing biological properties, such as insecticidal, mitoinhibitory, and anti-MRSA activities. Owing to their impressive polycyclic ring system as well as the pharmacologically and agriculturally important biological profiles, indole diterpenoids have long become the subject of studies from various aspects including biosynthesis, structure– activity relationship, 6] biosynthetic genes, and action mechanism. The total synthesis of indole diterpenoids has also been addressed by many research groups, and a series of extensive studies by Smith and co-workers successfully led to the total syntheses of as many as seven indole diterpenes including 1 and 2, while synthetic efforts by other groups toward naturally occurring indole diterpenoids have, so far, not yet come to completion. 14] In their total synthesis of 1 and 2, the Smith research group achieved highly stereoselective construction of a trans-anti-trans CDE ring intermediate containing the C3/C4 contiguous quaternary stereocenters (one of the most challenging tasks for the total synthesis of indole diterpenoids), but required a considerably lengthy multistep sequence from a protected form of the Wieland–Miescher ketone to obtain the tricyclic fused ring system. We describe herein a novel total synthesis of paspalinine (1) together with a formal synthesis of paspalicine (2) that features not only a concise stereoselective formation of the CDE ring system but also a high-yielding convenient installation of the indole moiety and an efficient introduction of the C13 tertiary hydroxy group through allylic selenoxide rearrangement. Scheme 2 outlines our retrosynthetic analysis of 1 and 2. Paspalinine (1) possessing the C13 hydroxy group would be derived by oxidative migration of the C12/C13 double bond of

Total Synthesis of Bacilosarcins A and B

In the course of screening for plant growth regulators ofmicrobial origin, Igarashi and co-workers discovered twonovel herbicidal substances, bacilosarcins A and B, in theculture broth of the bacterium Bacillus subtilis TP-B0611isolated from intestinal contents of the sardine Sardinopsmelanostica. Extensive spectroscopic analyses and chemicalconversions allowed the elucidation of their structures as 1and 2, respectively (Scheme 1).

Concise synthesis of PM-94128 and Y-05460M-A

The enantioselective total synthesis of PM-94128, a potent cytotoxin of microbial origin, was accomplished by a concise nine-step sequence of reactions in 14% overall yield from N-Boc-l-leucine. The synthesis of Y-05460M-A, a one-carbon lower homologue of PM-94128, was also achieved from N-Boc-l-valine by the same approach, which enabled its stereochemical determination.

Expeditious Construction of the DEF Ring System of Thiersinine B

Construction of a DEF ring model of thiersinine B has been achieved from a Wieland-Miescher ketone derivative by a five-step sequence featuring a one-pot regioselective α-allylation of the starting α,β-unsaturated ketone via the Claisen rearrangement and a double dihydroxylation of a dienone intermediate.

Synthesis of (±)-terpendole E

The first synthesis of the racemate of terpendole E, a specific inhibitor of the mitotic kinesin Eg5, has been achieved from a known tricyclic dihydroxy ketone by a 13-step sequence that involves diastereoselective installation of its C3 quaternary stereocenter via a cyclopropyl ketone intermediate and Pd-mediated two-step construction of the indole ring moiety as the key transformations. Graphical Abstract The first synthesis of (±)-terpendole E has been accomplished via the Simmons–Smith cyclopropanation and an efficient two-step indole ring formation.

Total synthesis of aurachins C, D, and L, and a structurally simplified analog of aurachin C

The quinoline antibiotics aurachins C, D, and L, and a structurally simplified analog of aurachin C were synthesized from 1-(2-nitrophenyl)butane-1,3-dione via reductive cyclizations of δ-nitro ketone intermediates, with zinc or iron as key steps. The results of antimicrobial tests indicate that the N-hydroxyquinolone nucleus mimics the electron carrier in the respiratory chain more strongly than the quinoline N-oxide nucleus.

Substrate specificity of the aspartate:alanine antiporter (AspT) of Tetragenococcus halophilus in reconstituted liposomes

The aspartate:alanine antiporter (AspT) of the lactic acid bacterium Tetragenococcus halophilus is a member of the aspartate:alanine exchanger (AAEx) transporter family. T. halophilus AspT catalyzes the electrogenic exchange of l-aspartate1− with l-alanine0. Although physiological functions of AspT were well studied, l-aspartate1−:l-alanine0 antiport mechanisms are still unsolved. Here we report that the binding sites of l-aspartate and l-alanine are independently present in AspT by means of the kinetic studies. We purified His6-tagged T. halophilus AspT and characterized its kinetic properties when reconstituted in liposomes (Km = 0.35 ± 0.03 mm for l-aspartate, Km = 0.098 ± 0 mm for d-aspartate, Km = 26 ± 2 mm for l-alanine, Km = 3.3 ± 0.2 mm for d-alanine). Competitive inhibition by various amino acids of l-aspartate or l-alanine in self-exchange reactions revealed that l-cysteine selectively inhibited l-aspartate self-exchange but only weakly inhibited l-alanine self-exchange. Additionally, l-serine selectively inhibited l-alanine self-exchange but barely inhibited l-aspartate self-exchange. The aspartate analogs l-cysteine sulfinic acid, l-cysteic acid, and d-cysteic acid competitively and strongly inhibited l-aspartate self-exchange compared with l-alanine self-exchange. Taken together, these kinetic data suggest that the putative binding sites of l-aspartate and l-alanine are independently located in the substrate translocation pathway of AspT.

Partial Racemization Occurring in the Hydroxylactonization of a δ,ε-Epoxy Amide

Acid-promoted hydroxylactonization of a δ,ε-epoxy amide took place via both 6-exo-tet and 7-endo-tet processes, causing a considerable degree of racemization of the resulting δ-hydroxyalkyl-δ-lactone.