Laboratory for SYNTETIC ORGANIC CHEMISTRY


Yoshiki Morimoto (Professor)


http://www.sci.osaka-cu.ac.jp/chem/org2/index.html




1. Current Research and Principal Research Interests

Our principal research interests include total synthesis, structural elucidation, biosynthesis, and mechanism of action for biologically active and structurally unique natural products, asymmetric synthesis, organometallic chemistry, reaction mechanism, and conformational analysis.

(1)    Total Synthesis and Complete Assignment of the Stereostructures of Squalene-Derived Cytotoxic Triterpene Polyethers (Oxasqualenoids)

Total Synthesis and Complete Assignment of the Stereostructure of a Cytotoxic Bromotriterpene Polyether (+)-Aurilol: The plane structure and partial stereochemistry of a cytotoxic bromotriterpene polyether (+)-aurilol (1), isolated from the sea hare Dolabella auricularia, were mainly elucidated by NMR methods; however, determination of the entire stereochemistry has not been reached. Although there have also been many other types of triterpene polyethers, it is often difficult to determine their stereostructures even by the current highly advanced spectroscopic methods, especially in acyclic systems including quaternary carbon centers such as C10–C11, C14–C15, and C18–C19 in 1. In this paper, we report that the total assignment of the incomplete stereostructure of (+)-aurilol (1) to the structural formula 2 has been accomplished through its first asymmetric total synthesis featuring the highly regio- and stereocontrolled biogenetic-like A–D ether ring formations.
Complete Assignment of the Stereostructure of a New Squalene-Derived Epoxy Tri-THF Diol from Spathelia glabrescens by Total Synthesis: The total assignment of the incomplete stereostructure of a new squalene-derived epoxy tri-tetrahydrofuran (THF) diol (3) to the structural formula 4 has been achieved through the first asymmetric syntheses of (22S)-4 and its epimer (22R)-5.


Total Synthesis and Determination of the Absolute Configuration of (–)-Longilene Peroxide: The first asymmetric total synthesis of (–)-longilene peroxide (6) has been achieved starting from the optically active C2-symmeric diepoxide through the concept of two-directional synthesis utilizing its intrinsic molecular symmetry. Thus, the unknown absolute configuration of longilene peroxide has been determined by this synthesis as shown in the structural formula 6.


(2)    Total Synthesis of Biologically Active and Structurally Interesting Nitrogen-Containing Natural Products
Total Synthesis and Assignment of the Double-Bond Position and Absolute Configuration of (–)-Pyrinodemin A: The first asymmetric total synthesis of a structurally novel cis-cyclopent[c]isoxazolidine alkaloid, (–)-pyrinodemin A (7), which exhibits potent cytotoxicity, has been accomplished through a highly diastereoselective intramolecular nitrone-olefin cycloaddition reaction as the key step. Thus, it has been found that the hitherto unknown absolute configuration of pyrinodemin A is as indicated in the structural formula 7.


Total Synthesis and Determination of the Stereochemistry of 2-Amino-3-cyclopropylbutanoic Acid, a Novel Plant Growth Regulator Isolated from the Mushroom Amanita castanopsidis Hongo: The unknown stereostructure of 2-amino-3-cyclopropylbutanoic acid 8, a novel plant growth regulator isolated from the mushroom Amanita castanopsidis Hongo, was determined to be (2S,3S)-9 through its racemic and enantioselective syntheses employing the chelate-enolate Claisen rearrangement as a key step.


Stereocontrolled Total Synthesis of the Stemona Alkaloid (–)-Stenine: The Stemona alkaloid stenine (10), isolated from Stemona tuberosa of physiologically active stemonaceous plants, possesses the structurally novel and unique azepinoindole skeleton (B,C,D-ring system). We have accomplished the asymmetric total synthesis of (–)-stenine (10), starting from 1,5-pentanediol. The key features are an intramolecular diastereoselective Diels-Alder reaction of the (E,E,E)-triene 11, prepared in a convergent fashion from three readily available compounds, and efficient construction of the tricyclic A,B,D-ring system through thermodynamically controlled regioselective enolization of the bicyclic ketone 12.


2. Selected Publications

1. “Reagent-Controlled Switching of 5-Exo to 6-Endo Cyclizations in Epoxide Openings”, Y. Morimoto, Y. Nishikawa, C. Ueba, and T. Tanaka, Angew. Chem., Int. Ed., in press.

2. “Structures, Biological Activities, and Total Syntheses of 13-Hydroxy- and 13-Acetoxy-14-nordehydrocacalohastine, Novel Modified Furanoeremophilane-Type Sesquiterpenes from Trichilia cuneata”, M. Doe, T. Shibue, H. Haraguchi, and Y. Morimoto, Org. Lett., 7, 1765–1768 (2005).

3. “Total Synthesis and Complete Assignment of the Stereostructure of a Cytotoxic Bromotriterpene Polyether (+)-Aurilol”, Y. Morimoto, Y. Nishikawa, and M. Takaishi, J. Am. Chem. Soc., 127, 5806–5807 (2005).

4. “Total Synthesis and Assignment of the Double-Bond Position and Absolute Configuration of (–)-Pyrinodemin A”, Y. Morimoto, S. Kitao, T. Okita, and T. Shoji, Org. Lett., 5, 2611–2614 (2003).

5. “Total Synthesis of (+)-Eurylene and (+)-14-Deacetyl Eurylene”, Y. Morimoto, K. Muragaki, T. Iwai, Y. Morishita, and T. Kinoshita, Angew. Chem., Int. Ed., 39, 4082–4084 (2000).

6. “Revised Structure of Squalene-Derived PentaTHF Polyether, Glabrescol, through Its Enantioselective Total Synthesis: Biogenetically Intriguing CS vs C2 Symmetric Relationships”, Y. Morimoto, T. Iwai, and T. Kinoshita, J. Am. Chem. Soc., 122, 7124–7125 (2000).

7. “Can α-Sultone Exist as a Chemical Species? First Experimental Implication for Intermediacy of α-Sultone”, Y. Morimoto, H. Kurihara, and T. Kinoshita, Chem. Commun., 189–190 (2000).

8. “Effective Combination of Two-Directional Synthesis and Rhenium(VII) Chemistry: Total Synthesis of meso Polyether Teurilene”, Y. Morimoto, T. Iwai, and T. Kinoshita, J. Am. Chem. Soc., 121, 6792–6797 (1999).

9. “Highly Diastereoselective Cylizations of Bishomoallylic Tertiary Alcohols Promoted by Rhenium(VII) Oxide. Critical Steric versus Chelation Effects in Alkoxyrhenium Intermediates”, Y. Morimoto and T. Iwai, J. Am. Chem. Soc., 120, 1633–1634 (1998).

10. “Studies on the Asymmetric Synthesis of Stemona Alkaloids: Total Synthesis of (–)-Stenine”, Y. Morimoto, M. Iwahashi, K. Nishida, Y. Hayashi, and H. Shirahama, Angew. Chem., Int. Ed. Engl., 35, 904–906 (1996).