本論文は,著者らの開発した新しいヒドロシアン化反応の天然物,とくに多環式構造を有するステロイド,ジテルペン,あるいはそれらのアルカロイドの合成に対する有用性について述べている。新ヒドロシアン化法によって,多環式構造を有する共役ケトン体から目的に応じ立体的に有利に核間位にシアン化されたケトン体をえることができる。核間位シアン基は,他の種々の炭素置換基に変換されるし,またそれによって天然物に多く含まれる橋状環系の合成も容易に行なわれうる。したがって新ヒドロシアン化反応は一般に困難と考えられている核間位に炭素置換基を導入したり,また橋頭炭素の一つを核間位に有する橋状環の組み立てめ問題に一つの有力な手段を提供している。新ヒドロシアン化反応は,アルキルアルミニウム (R₃Al) とシアン化水素の組み合わせ (A法) ,あるいはシアン化ジアルキルアルミニウム (R₂AlCN) (B法) によって行なわれ,そのヒドロシアン化の効率は高い。核間位シアン化の場合の立体経路は用いる共役ケトンの構造に左右されるが,trans-または,cis-シアソケトンのいずれが優先的に生成するかは,多くの例からえられた経験則,あるいは理論的考察からある程度予知することができる。つぎに核間シアソ基の他の炭素置換基,たとえばカルボキシル基,イミノメチル基,アミノメチル基,ホルミル基,メチル基,ヒドロキシメチル基への適切な変換法が確立された。またシアンケトンから他の橋状環,たとえばピロリジン,ピペリジン,ピシクロ [3.2.1] ,あるいは [22.2]オクタン環系の組み立て法も研究された。この結果を応用して種々の天然物,たとえば二三のプレグナン系ステロイド,またはそのアルカロイドであるラチホリン,ジテルペンアルカロイドであるアチシン,ガリン,ビーチンなどが合成された。

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Zur Darstellung des 6-Methoxy-3, 4-dihydronaphthalins (IV) wurde die Bamford'sche Reaktion angewandt und deren Vorzuge nachgewiesen. Zur Synthese des 6-Methoxy-3, 4-dihydro-2 (1H)-naphthalinons (VII) aus (IV) wurde eine Methode, die zwar ursprunglich von Salzer stammte, aber wesentlich verbessert wurde, festgestellt.

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Persaureoxydation von 6-Methoxy-3, 4-dihydronaphthalin (I) verlief unter einer abnormalen Aufspaltung des intermediar entstandene Epoxides und ergab ein Gemisch von cis- und trans-Monoacyldiolen, bevorzugt mit dem ersteren. Das Entstehen von cis-1-Acetoxy-2-benzoyloxy-6-methoxy-1, 2, 3, 4-tetrahydronaphthalin (IIIa) bei der Oxydation mit Benzopersaure und bei der nachtraglichen Acetylierung ist durch eine intramolekulare Umesterung des zuerst entstehenden cis-1-Monobenzoates (XIVa) (R=Phenyl) erklarbar. Eine derartige Wechselwirkung des cis-1, 2-Diolderivates wurde auch beim cis-Diacetat (IIa) beobachtet. Trans-Diol (VIIIb) ergab durch Einwirkung von Aceton oder p-Nitrobenzaldehyd cis-Dioxoran-Verbindungen (IX oder X). Diese abnormalen Ergebnisse konnen durch Annahme der auβerst stabilen C₁-Carboniumionen und der Wechselwirkung der cis stehenden benachtbaren Substituenten sehr gut erklart werden.

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N-Sulfonylated 3-methoxycholestane (5→3)-lactams (Vc), (VIc) and (VId) were subjected to reductive fragmentation initiated with lithium aluminum hydride giving in good yields N-sulfonylated cis-amino alcohols (3α, 5α and 3β, 5β) (XIIIa), (XIVc), and (XIVa). These compounds were smoothly cyclized to 3α, 5-iminomethano-5α-and 3β, -5-iminomethano-5β-cholestane derivatives, (Ia), (IIa), and (IIb), which were then desulfonylated to give 3α, 5α-and 3β, 5β-pyrrolidinocholestanes (Ib) and (IIc), respectively.

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Steroidal derivatives having a bicyclo [3. 2. 1] octane bridged ring of the phyllocladene type on the A ring such as compounds (IVa), (IVb), (XXIV) and (VIIIa) were synthesized starting from 5α-cyanocholestan-3-one by three routes. The route consisting of conversion of the cyano group into an acetyl group, and subsequent cyclization was found to be most preferable for the synthesis.

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trans-9-Methyl-(XIa) and -9-aminomethyl-2-decalones (VIII) were prepared from the parent trans-2-oxo-9-decalincarbonitrile (I) by a series of reductions and were characterized.

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Progress in synthetic studies on 1-oxacephems is reviewed. Antibacterial activity of this new class of compounds is also discussed briefly. Earlier syntheses, rather lengthy but quite pioneering, provided us with valuable information of the interesting biological activity of 1-oxacephems. Several improved synthesis have appeared, enabling to prepare a variety of derivatives and examine their antibacterial activity. Thus, syntheses and antibacterial activity of some interesting 1-oxacephems and 7α-methoxy-1-oxacephems, such as, arylmalonamido-, α-acylureidophenylacetamido-, and α-aminothiazolyl-α-methoxyiminoacetamido derivatives with representative 3'-substituents are described. A compound 6059-S 98 discovered in Shionogi Research Laboratories, proved to have excellent antibacterial activity, spectrum, and other pharmacological properties and, therefore, is currently under clinical studies. An industrially feasible synthetic method for its nucleus 88 a as well as 7α-methoxy-1-oxacephem nuclei with a variety of substituents at the 3'-position in general was established after extensive studies.

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Following considerations were made regarding the so-called second-type Beckmann rearrangement by which nitrile is formed from ketoxime.
1) Such rearrangement easily occurs with compounds in which C-C bond (C-H bond in aldoxime) in the transposition of the oxime group is easily cleaved.
2) Such rearrangement was confirmed to occur primarily by cleavage without passing through an intermediate of acid aride or imide, by detailed studies on camphor oxime and anti-α-isonitrosocamphor.
3) It was pointed out that the rearrangement agent does not directly attack the β-carbon, the carbon atom next to the carbon bonding with nitrogen.

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Cholestane derivative (IIb) having a bridged 3-azabicyclo [3. 3. 1] nonane ring system was synthesized from 3-oxo-5α-cholestane-5-carbonitrile (III) by a six-step reaction sequence. The over-all yield was very high indicating high stereospecificity or uniformity of the reaction used. Reduction of 3α-formyl-3β-methyl-5α-cholestane-5-carbonitrile (VIII) to the amino alcohol (Xa) was effected by means of lithium aluminum hydride reduction in the presence of aluminum chloride.

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Some steroidal compounds having a bridged bicyclo [3. 2. 1] octane ring system of the kaurene type were syntheiszed starting from the bridged compound (VIa) of the phyllocladene type by two different routes. The major subject of this work is to convert the bridged system of the phyllocladene type into that of the kaurene tupe. The Wagner-Meerwein type rearrangement was successfully applied for this purpose as exemplified by the coversions XVd-XIV and XXII-XXIII. The allylic alcohol function was also successfully introduced into the bridged five-membered ring.

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Cyanation at the angular position of ⊿^{1, 9}-2-octalone (I) was conducted with potassium cyanide in the presence of ammonium chloride in polar solvent, or with hydrogen cyanide and triethyl aluminum in tetrahydrofuran. In the latter case, high stereospecificity of the reaction was observed and the formation of trans-2-oxo-9-decalincarbon-itrile (IIa) to its cis-isomer IIIa was in a ratio of 24 : 1. The structures and the configurations of the products were determined by conversion into the known trans- XII and cis-9-decalincarboxylic acid (XIII). Moreover the stereochemistry of this cyanation reaction was discussed.

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