A number of bioactive compounds, which are presumably biosynthesized through Diels-Alder reaction in plants and microorganisms, have been found. However, no direct evidences for the reaction was obtained. Biosynthetic studies have been performed to prove the hypothesis with a few phytotoxins. Feeding experiments of solanapyrone A with labelled precursors, and the isolation and the synthesis of the diastereomer, solanapyrone D, strongly suggest the participation of biological Diels-Alder reaction. The treatment of P. betae with cytochrome P-450 inhibitors accumulated an intermediate, probetaenone I, which structure was confirmed by the synthesis. The same treatment of C, subaffine accumulated prochaetoglobosins. These are also evidences for biological Diels-Alder reaction. Chemical synthesis of diplodiatoxin and betaenone C have made possible to provide key intermediates for incorporation study of biological Diels-Alder reaction.

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Recent advances in the field of the β-lactam ring syntheses in the last decade are reviewed. All the methods are classified according to the notation of m + n _??_ 4 cyclization (m and n = 0, 1, 2, 3, …). Each reaction is briefly commented.

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Anthracycline antibiotics, represented by daunorubicin and doxorubicin, are important antitumor agents widely used in clinical treatment. Their use is, however, restricted by the cardiotoxic character and other undesirable side-effects. To overcome these drawbacks and expand the utility, many efforts have been made for the past two decades. Recently we have synthesized a compound with strong antitumor activity and weak toxicity, 7-O- (2, 6-dideoxy-2-fluoro-α-L-talopyranosyl) adriamycinone, in which the glycosidic bond is comparatively stable in acid-catalyzed hydrolysis by the presence of highly electronegative fluorine atom at C-2'. This article describes the recent studies on the synthesis of the 2'-fluoroanthracycline antibiotics and their 14, 3', and 4'-substituted derivatives together with structure-activity relationship. It was found that R-configuration at C-2' having the fluorine is requisite to exhibit strong antitumor activity; thus (2'S) -fluoro and 2', 2'-difluoro analogs were devoid of activity. Synthesis of 2'-methoxyl analogs is also described.

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Studies on the synthesis of isocarbacyclin [9 (O) -methano-Δ^{6 (9a)} -prostaglandin I₁], a stable prostacyclin analogue, were carried out starting from bicyclic synthons which were prepared from a chiral 4-hydroxy-2-cyclopentenone via three-component coupling process. We elabolated several methodologies, which involved regioselective or regiospecific alkylation reactions by use of various transition metal catalysts : (1) regioselective alkylation of bicyclic allylic alcohol synthons with alkyllithium in the presence of copper (I) salt and aminophosphonium salt, (2) regiospecific alkylation of bicyclic carbonate synthons with bissulfone derivative in the presence of palladium catalyst, and (3) regioselective alkylation of bicyclic phosphate synthons with zinccopper reagent. In addition, several deuterium- or tritium-labeled isocarbacyclin derivatives were also synthesized by the use of these methodologies.

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Etofenprox 1 (experimental code number : MTI-500) is a new synthetic insecticide discovered and developed by Mitsui Toatsu Chemicals, Inc.
In 1978, we began searching a compound with low toxicity to fish as to be used in paddy fields, and after two years, we found a second lead compound 16. We tried to optimize the skeleton of compound 16, and as a result, 2- (4-ethoxyphenyl) -2-methylpropyl 3-phenoxybenzyl ether was selected as a candidate for development. It is now registered for agricultural use in Japan and some countries in Southeast Asia. Etofenprox 1 is low in acute mammalian toxicity and fish toxicity, and has several favorable properties compared with conventional insecticides.

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[in Japanese]

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