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Oxygen atoms have a lone pair of electrons, so they have high chelation ability, high nucleophilic ability, stabilizing ability of adjacent cations, and take a chelate or oxocarbenium ion structure with Lewis acids and metals. I took advantage of these properties to develop three new reactions, 1) asymmetric synthesis of chiral quaternary carbon centers, 2) asymmetric synthesis using acetal functions, and 3) organic chemistry using acetal-type reactive salt chemical species, and applied them to biologically active natural products synthesis. New reactions described here are all innovative and useful for natural products synthesis. In particular, the first asymmetric synthesis of fredericamycin A, and concise asymmetric synthesis of anthracycline antibiotics, scyphostatin, (+)-Sch 642305, (-)-stenine, clavolonine, (+)-rubrenolide, (+)-rubrynolide, (+)-centrolobine, and decytospolide A and B, etc., are noteworthy. Furthermore, since reactions using acetal-type reactive salt chemical species allow the coexistence of functional groups that normally cannot coexist, the reactions using reactive salts have potential to change the retrosynthesis planned based on conventional reactions.

A gold-catalyzed introduction of various terminal alkynes to acetals was investigated. Extensive optimization of the reaction conditions revealed that thermally stable cationic gold catalysts bearing bulky ligands such as 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene 3-1H-benzo[d][1,2,3]triazolyl gold trifluoromethanesulfonate (IPrAu(BTZ-H)OTf) were particularly suitable for the reaction. Additionally, significant solvent effects were observed. Ether solvents such as tetrahydrofuran (THF), cyclo pentyl methyl ether (CPME), and 1,4-dioxane were effective for the reaction. Studies on the scope of substrates and alkynes indicated that various alkynes and acetals were feasible to provide a wide range of propargylic ethers.

A convenient method for the preparation of alkynes and alkynyl esters from ketones and β-keto esters is described which involves the formation of vinyl triflates, followed by elimination with tetrabutylammonium fluoride trihydrate, to give alkynes. Unlike established elimination methods, the method requires neither a strong base nor anhydrous conditions.

A concise synthesis of a useful intermediate 10 for the preparation of fingolimod (FTY-720) analogs was achieved by utilizing a chemoselective Sonogashira reaction of trihalobenzene 12 with alkyne 13. The reaction proceeded with high selectivity to give alkyne 11 containing the dihalobenzene moiety in good yield. Compound 11 was converted into intermediate 10 by hydrogenation without reduction of the halogen atoms.

Direct scandium- and lanthanum-catalyzed etherifications of propargyl alcohols 1 and 6 in MeNO₂-H₂O provided propargyl ethers 3, 4 and 7 in high yields. In addition, reactions of 1 and 6 with thiols exclusively yielded the corresponding propargyl sulfides.

Diethyl alpha-alkynyl-alpha-methoxymalonates (2a--e) were smoothly hydrolyzed and then decarboxylated under alkaline conditions employing 1 N KOH in EtOH to give conjugated allenyl esters (6a--e) in high yields, and similar alkaline treatment of diethyl alpha-alkynyl-alpha-acetylaminomalonates (5a, b, d, e) furnished unexpectedly the oxazoles (7a, b, d, e) having three substituent groups in excellent yields.

A new polyacetylene, gymnasterkoreayne G (1) and seven known (2--8) constituents were isolated from the leaves of Gymnaster koraiensis. Base on extensive 1D and 2D NMR spectroscopic data, the structure of the new compound was identified as erythro-8(S)-9(Z),16-heptadecadiene-4,6-diyne-2,3,8-triol. Isolated compounds were evaluated for their ability to inhibit NFAT transcription factor. While other components did not show activity, most of polyacetylene components markedly inhibit NFAT transcription factor. Of these compounds, gymnasterkoreayne B (3) was the most potent (IC(50) 1.44+/-0.59 microM). In term of the isomers, compound 1 (IC(50) 43.9+/-2.24 microM) with an erythro-configuration showed less inhibition than 2 (IC(50) 7.24+/-0.42 microM) with a threo-configuration.

Acetylpanaxydol (1-Ac), PQ-3 (2) and panaxydiol (3) and their optical isomers were synthesized from L-(+)-diethyl tartrate. The absolute configurations of 1-Ac, 2 and 3 were determined to be 1-Ac (3R,9R,10S), 2 (9R,10S) and 3 (3R,10S), respectively, by comparisons of their optical rotations and the NMR data of their MTPA esters with those of natural products.

The sequential Sonogashira reaction and the cyclization reaction of various 2-iodoanilines and terminal alkynes in the presence of a palladium catalyst and tetrabutylammonium fluoride (TBAF) gave the corresponding 2-substituted indoles in good yields.

Repandiol, a new cytotoxic diepoxide has been isolated from the mushrooms Hydnum repandum and H. repandum var. album. The chemical structure was elucidated as (2R,3R,8R,9R)-4,6-decadiyne-2,3:8,9-diepoxy-1,10-diol on the basis of spectroscopic analysis. The structure was confirmed by the synthesis of optically active repandiol. Repandiol displayed potent cytotoxic activity against various tumor cells.

A series of N-(4-amino-2-butynyl)acetamides were synthesized and examined for their inhibitory activity on detrusor contraction and mydriatic activity as an index of anticholinergic side effect. Among those compounds synthesized, (+)-2-cyclohexyl-N-(4-dimethylamino-2-butynyl)-2-hydroxy-2-phenylacet amide hydrochloride ((+)-13b.HCl), 2-cyclohexyl-2-hydroxy-N-(4-methylamino-2-butynyl)-2-phenylacetamide+ ++ hydrochloride (13c.HCl), N-(4-dimethylamino-2-butynyl)-2,2-diphenyl-2-hydroxyacetamide hydrochloride (14a.HCl), and 2,2-diphenyl-N-(4-ethylamino-2-butynyl)-2-hydroxyacetamide hydrochloride (14b.HCl) showed equipotent inhibitory activity on detrusor contraction to oxybutynin (1) and less mydriatic activity. Further evaluation of these compounds as an agent for the treatment of overactive detrusor has been examined.

Panaxacol (1) and dihydropanaxacol (2), cytotoxic polyacetylenes isolated from the callus of Panax ginseng, were synthesized starting from D-(-)-diethyl tartrate. The absolute configuration of 1 was determined to be 9R, 10R and the absolute configuration at C-3 of 2 was tentatively assigned as 3S by the application of the R(+)-alpha-methoxy-alpha-(trifluoro methyl)phenylacetyl (MTPA) method.