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The reactions of dialkylphenylsulfonium salts (1) with several nucleophiles such as phenols, amine, enolate ion, and thiolate ions, have been investigated. The relative reactivities of the alkyl groups of sulfonium salts for the phenolate ion (hard nucleophile) were as follows; Me:Et:i-Pr =1.0:1.34:3.44. In the alkylation of the p-toluenethiolate ion (soft nucleophile) with 1, the opposite reactivity (Me:Et:i-Pr=1.0:0.22:0.03) was found. When a sulfonium salt (1e) having an optically active (S)-s-butyl group was reacted with a phenolate ion, an optically active (R)-s-butyl phenyl ether was obtained with an inversion of the configuration at the chiral carbon atom. A reaction mechanism via a sulfurane intermediate is proposed for the alkylation of the phenolate ion with alkylsulfonium salts. The relative reactivities for the alkylation of several nucleophiles with dialkylphenylselenonium salts (12) were also investigated.

The convenient syntheses of various thiazole α-dehydroamino acids, thiazole valine ethyl ester, and their dehydrodiand tripeptides, which are important moieties and segment of micrococcin P1 and noshiheptide, macrocyclic peptide antibiotics, were first accomplished.

The stereoselective synthesis of an amino acid component called Fragment D, N,O-diprotected 2-[(1S,3S)-1-amino-3-carboxy-3-hydroxypropyl]thiazole-4-carboxylic acid of a macrobicyclic peptide antibiotic nosiheptide, was achieved by two routes. The dipeptide, Fragment B-C, 2-[(Z)-1-(N,O-isopropylidene-L-threonylamino)-1-propenyl]thiazole-4-carboxylic acid was also synthesized by the thiazole ring formation from (Z)-2-(N,O-diprotected L-threonylamino)-2-butenethioamide with ethyl bromopyruvate. The coupling of two components by using a condensing agent gave the expected tripeptide 2, which is an important partial skeleton of the nosiheptide.

The novel antifungal karnamicin B1 (1), 5-hydroxy-3,4-dimethoxy-2-{2-(4-oxopentyl)-4-thiazolyl}pyridine-6-carboxamide was first synthesized via the formation of partially methylated trihydroxy pyridine by ring-transformation from the corresponding furan derivative and subsequent regioselective introduction of 2,6-substituents using Meisenheimer-type reaction.

Fragment A derivative (13) of nosiheptide, useful for the total synthesis, was obtained by stepwise introduction of the 2,5-bis{(4-ethoxycarbonyl)-2-thiazolyl} groups and 6-{(2-substituted)-4-thiazolyl} group into 3-hydroxy-5-cyanopyridine(3). The total yield was 7.6% via 14 steps.

The central heterocylic skeleton (13) of an antibiotic, A10255, was synthesized by stepwise introduction of two groups into the 2,6-positions of 3-{(4-ethoxycarbonyl)-2-thiazolyl} pyridine, via 17 steps in 4.8% total yield.

Two 4-ethoxycarbonyl thiazolyl groups were introduced into 2- and 5-positions of 3-hydroxypyridine in 8 steps using 5-cyano-3-hydroxypyridine (2) as the starting material. The pyridine derivative obtained in the last step was converted to a fragment A derivative (21) by stepwise introduction of the 2-substituted 4-thiazolyl group into the 6-position. The total yield for the formation of 21 via 14 steps was 7.6%.

It was shown that 6-dimethoxymethyl-1,2-dihydro-2-oxo-3-pyridinecarbonitrile (5) is easily convertible into the titled ring system by a stepwise method. Both the 3-cyano and 6-dimethoxymethyl groups of 5 were converted into 2-thiazolyl groups via the thioamide and carbaldehyde groups by Hantzsch and Shioiri methods, respectively. The 2-pyridone function was changed to a bromoacetyl group via the coupling reaction between the corresponding triflate and ethyl vinyl ether, and then converted into the 4-thiazolyl group. Thus, the useful 3,6-di(2-thiazolyl)-2-(4-thiazolyl)pyridine derivative for the total synthesis of GE 2270 A was obtained. In fact, the method was recently applied to the total synthesis of an antibiotic, micrococcin P, which has a similar central skeleton.

Alkylation of the enolate anion of 2-methoxycarbonyl-1-indanone with optically active dialkylphenyl selenonium salt resulted in the formation of optically active C-alkylated products. Absolute configuration of the optically active selnonium ion was estimated on the basis of the asymmetric alkylation and CD spectra.

The asymmetric alkylation of 2-methoxycarbonyl-1-indanone (2) and ethyl 2-methylacetoacetate (5) with an alkylsulfonium salt containing a sugar group were investigated. (S)-Ethyl 2-allyl-2-methylacetoacetate (6b) was obtained with up to 25% optical purity on alkylation of the enolate ion of 5 using the allyl(p-tolyl)sulfonio D-glucoside derivative (1h).

Alkylation of cyclic β-keto ester with racemic sulfonium salts containing optically active alkyl groups such as (S)-2-octyl and (S)-2-butyl was found to afford C-alkylated products with inversion of configuration at asymmetric alkyl carbon atom. Stereochemical reaction course via formation of S–O sulfurane intermediate and successive stereoselective intramolecular alkyl migration to enolate is described.