Hiroyoshi Takamura

Total synthesis of brevenal

A total synthesis of brevenal is described. The pentacyclic ether core was constructed by the intramolecular allylation of alpha-acetoxy ether and subsequent ring-closing metathesis. Both of the diene side chains were introduced by Wittig olefination and a Horner-Wadsworth-Emmons reaction, respectively, in a highly stereoselective manner.

Syntheses of the AB and EFGH ring segments of gambierol

Abstract Stereocontrolled syntheses of the AB and EFGH ring systems of gambierol ( 1 ) are described. The two key intermediates 3 and 55 , representing the AB and EFGH ring frameworks, were prepared from 2-deoxy- d -ribose via linear sequences. Browns asymmetric allylboration and the intramolecular hetero-Michael reaction were successfully applied to the construction of the A ring moiety. Synthesis of the EFGH ring segment 55 was achieved by the SmI 2 mediated reductive cyclization, constructing the EF ring bearing two 1,3-diaxial methyl groups, and the palladium catalyzed coupling of enol triflate and zinc bishomoenolate, making the GH ring moiety. Attempted convergent approaches toward the EFGH ring framework are also described.

Synthesis of the J ring segment of gambieric acid

Abstract The J ring segment 2 of gambieric acid was synthesized stereoselectively by the coupling between the cyclic ether component 3 and the alkenyl iodide 4 . The tetrahydropyran 3 was stereoselectively synthesized by the 6- endo -cyclization of a hydroxyepoxide prepared from deoxy- d -ribose. The side chain moiety 4 was prepared by the stereoselective hydrostannation of an internal alkyne.

Synthesis and Structural Revision of Symbiodinolide C23-C34 Fragment

Stereoselective synthesis of the C23-C34 fragment of symbiodinolide, which possesses the originally proposed stereochemistry, and its diastereomers was achieved in 19 steps from L-aspartic acid, respectively. Comparison of spectroscopic data of the synthetic products with those of the degraded product of symbiodinolide led to a structural revision of the C23-C34 fragment.

Concise synthesis of cyclic ethers via the palladium-catalyzed coupling of ketene acetal triflates and a zinc homoenolate. Synthesis of the DE and GH ring segments of gambierol

Abstract Concise syntheses of the DE and GH ring segments of gambierol ( 1 ) were achieved by the palladium-catalyzed coupling of ketene acetal triflates and a zinc homoenolate, followed by the hydroboration of the resulting cyclic enol ethers and subsequent lactonization.

Stereoselective synthesis and absolute configuration of the C33–C42 fragment of symbiodinolide

Abstract Cross-metathesis of methyl ester which was prepared from symbiodinolide with ethylene was performed to give the C33–C42 degraded fragment. This fragment was estimated to be (36 S ,40 S )-diol by the modified Mosher method. Stereoselective synthesis of the (36 S ,40 S )-diol and its diastereomer (36 R ,40 S )-diol was achieved from l -aspartic acid. Synthetic bis-( S )- and ( R )-MTPA esters which were derivatized from the (36 S ,40 S )-diol exhibited spectroscopic data identical with those of bis-( S )- and ( R )-MTPA esters derived from the degraded product. Thus, the absolute stereochemistry of the C33–C42 fragment was elucidated to be (36 S ,40 S ).

Synthetic studies towards gambierol. Part 2: Synthesis of the EFGH ring segment

Abstract The EFGH ring segment of gambierol was synthesized from 2-deoxy- d -ribose in 40 steps. The present synthesis includes a SmI 2 -mediated reductive cyclization and a Pd-catalyzed coupling of enol triflate with a zinc bis-homoenolate as key steps.

Chemical control of xylem differentiation by thermospermine, xylemin, and auxin

The xylem conducts water and minerals from the root to the shoot and provides mechanical strength to the plant body. The vascular precursor cells of the procambium differentiate to form continuous vascular strands, from which xylem and phloem cells are generated in the proper spatiotemporal pattern. Procambium formation and xylem differentiation are directed by auxin. In angiosperms, thermospermine, a structural isomer of spermine, suppresses xylem differentiation by limiting auxin signalling. However, the process of auxin-inducible xylem differentiation has not been fully elucidated and remains difficult to manipulate. Here, we found that an antagonist of spermidine can act as an inhibitor of thermospermine biosynthesis and results in excessive xylem differentiation, which is a phenocopy of a thermospermine-deficient mutant acaulis5 in Arabidopsis thaliana. We named this compound xylemin owing to its xylem-inducing effect. Application of a combination of xylemin and thermospermine to wild-type seedlings negates the effect of xylemin, whereas co-treatment with xylemin and a synthetic proauxin, which undergoes hydrolysis to release active auxin, has a synergistic inductive effect on xylem differentiation. Thus, xylemin may serve as a useful transformative chemical tool not only for the study of thermospermine function in various plant species but also for the control of xylem induction and woody biomass production.

Total Synthesis of Two Possible Diastereomers of (+)-Sarcophytonolide C and Its Structural Elucidation

Stereoselective and parallel total syntheses of two possible diastereomers of (+)-sarcophytonolide C have been accomplished. Macrolactonization and transannular ring-closing metathesis (RCM) were the key transformations. Detailed comparisons of their (1)H and (13)C NMR data and specific rotation with those of the natural product allowed the absolute configuration of (+)-sarcophytonolide C to be determined.

Total synthesis, structural elucidation, and structure-cytotoxic activity relationship of (-)-gummiferol

A highly stereoselective and stereodivergent synthesis of two possible diastereomers of (-)-gummiferol was achieved, wherein the stepwise epoxidation and Cadiot-Chodkiewicz reaction were utilized for the construction of the diepoxide moiety and triacetylene part, respectively. Detailed comparison of their (1)H and (13)C NMR data and specific rotation with those of the natural product unambiguously elucidated the absolute stereostructure of gummiferol. In addition, the cytotoxic activity of the synthesized gummiferol, its stereoisomers, and its truncated analogues was evaluated, which clearly indicates that (1) the absolute configuration of the diepoxide moiety has little influence on the cytotoxic activity against human cancer cells and (2) the triacetylene unit is the crucial structural element required for exerting the cytotoxic activity.