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Two arylsulfatase-producing streptomycetes that desulfated etoposide 4'-sulfate were isolated from soil samples. Taxonomical study identified one soil isolate as Streptomyces griseorubiginosus S980-14 (Es-1 arylsulfatase producer), while the other was considered new and tentatively designated Streptomyces sp. T109-3 (Es-2 arylsulfatase producer). Both strains produced extracellular arylsulfatase activities, provided that cultivation media were prepared with distilled water. Unlike the two known types of arylsulfatases, which had significant activity on p-nitrophenyl sulfate but none on etoposide 4'-sulfate, the crude streptomycete arylsulfatases efficiently desulfated etoposide 4'-sulfate and p-nitrophenyl sulfate, which supports the establishment of a new type of arylsulfatases.

A total synthesis of 6,7-dihydroeponemycin 2 was achieved via the epoxide intermediate 8a . Unresolved absolute configuration of the epoxide ring in 2 and eponemycin 1 was determined to be 2 R by application of the asymmetric Sharpless epoxidation of 9 .

The 2''-O-, 3''-O- and 2'',3''-di-O-substituted derivatives (4a--p) of etoposide were prepared by nucleophilic substitution of 4'-O-benzyloxycarbonyletoposide (2) followed by deprotection. Controlled reaction (a limited amount of reagents and low temperature) was required for preparing the mono-O-substituted derivatives. In terms of ED125 values, doses which show 125% of T/C against P388 leukemia in mice, both the 2''-O-acetate (4a, ED125 = 0.18 mg/kg) and 3''-O-acetate (4b, 0.23 mg/kg) were nearly as active as etoposide (1, 0.19 mg/kg), while the 2'',3''-di-O-acetate (4c, 1.9 mg/kg) was somewhat less potent. In the replacement with other substituents, antitumor activity of the 2''-O-substituted derivatives was affected much more by the difference of the substituents as compared with that of the corresponding 3''-O-substituted derivatives. In the 2'',3''-di-O-substituted derivatives, the activity was decreased additively on the substituents.

By means of a model electrode method, it has been found that the ruthenium oxide highly dispersed on glassy carbon produces an extremely large surface charge density which corresponds to more than one proton adsorbs on every ruthenium loaded on the glassy carbon, if the charge was supposed to be caused only by the adsorption of proton on the RuO2.

As part of a search for new potent derivatives, electrochemical oxidation of etoposide (1) was carried out under controlled potential (500 mV) to yield 1,2-dehydroetoposide (4), 4'-O-demethyl-1,2,3,4-tetradehydro-4-dehydroxy-podophyllotox in (5) and 1,2,3,4-tetradehydroetoposide (6). They showed no cytotoxicity against B16-melanoma.

Controlled crisscross annulation was applied to the synthesis of (±)-dihydrodesoxyotonecine, a degradation product of secopyrrolizidine alkaloids.

The synthesis of the nuclei of pyrrolizidine and indolizidine could be readily achieved by use of the one pot reaction named as “crisscross annulation”, which was extended to the synthesis of (±)-heliotridane ( 16 ) and (±)-nuphar indolizidine ( 20 ), a minor component of dried scent glands of the Canadian beaver.

Etude de la reduction electrochimique sur electrode de mercure dans le DMF-tetrafluoroborate de tetraethylammonium, de la (bis-[benzyl tosyl amino]-2',5' p-tolyl-2 methyl-2 cyclopentanedione-1,3. Preparation de (benzyl-1 benzylamino-8 dimethyl-6,9 hexahydro-1,2,3,4,5,6) benzoazocine-1

Phoracantholide I, having a ten-membered lactone, was synthesized through a new synthetic method which includes a cyclic acetylenic oxy-Cope rearrangement and ring-expansion by the Baeyer-Villiger oxidation of a nine-membered ketone.

The crisscross annulation, developed towards synthesis of diverse nitrogen-containing heterocycles via a one-pot reaction, is remarkably effective in the construction of pyrrolo[1,2-α] indole derivatives (7 and 22) as the possible intermediates for syntheses of mitomycins. These were converted to mitosene derivatives (34 and 40) through the various repeated oxidation processes.

The arenesulfonyl group of sulfonamide (12) was efficiently removed by utilization of electrochemical reduction in a new cooperative system of anthracene and ascorbic acid, and subsequent electrogenerated bases were very effective to produce the 1-benzazocinone derivatives, in one pot, through the controlled crisscross annulation.

A synthesis of 9a-hydroxy-5,8-dideoxomitosanes was accomplished by the transannular cyclization of hydro-1-benzazocinone intermediates derived from 3-(2,5-dioxo-1-methylcyclopentyl)-6-methyl-p-phenylenediamine derivatives. These mitosanes were led to the 8-membered ring system by an oxidative ring-opening reaction.

Synthese de l'acetal-5 de la dimethyl-6,9 methoxy-8 octahydro-1,2,3,4,5,6,7,10 tosyl-1 benzoazocine-1 trione-5,7,10 a partir de benzyl-1 benzylamino-8 dimethyl-6,9 hexahydro-1,2,3,4,5,6 benzoazocine-1-dione-2,5

(±)-Tryptoquivaline G was formally synthesized through shortened steps from tryptophan, in which oxidation with thallium(III) trinitrate(TTN) was effected at the crucial stage. The present work also constitutes the first synthesis of oxindole lactones carrying 2-alkyl quinazolinones.

The new acylating agents [PhS(O)–CH=C(OMe)Cl and the corresponding sulfone] were proved to be useful for indroduction of an acetyl group into the α-position of the carbonyl group by means of two-carbon Michael acceptors, which was successfully applied to a total synthesis of (±)-aspidofractinine.

The crisscross annulation, developed towards synthesis of diverse nitrogen-containing heterocycles via a one-pot reaction, is remarkably effective in the construction of pyrrolo[1,2-α] indole derivatives (7 and 22) as the possible intermediates for syntheses of mitomycins. These were converted to mitosene derivatives (34 and 40) through the various repeated oxidation processes.

The new acylating agents [PhS(O)–CH=C(OMe)Cl and the corresponding sulfone] were proved to be useful for indroduction of an acetyl group into the α-position of the carbonyl group by means of two-carbon Michael acceptors, which was successfully applied to a total synthesis of (±)-aspidofractinine.

(±)-Deoxyaspidodispermine, whose (–)-form was isolated from Aspidosperma dispermum and demonstrated as formula (VIIa) of a unique constitution among Aspidosperma alkaloids, was first synthesized under stereocontrol to directly prove the correctness of the proposed structure by chemical means.

(±)-Deoxyaspidodispermine, whose (–)-form was isolated from Aspidosperma dispermum and demonstrated as formula (VIIa) of a unique constitution among Aspidosperma alkaloids, was first synthesized under stereocontrol to directly prove the correctness of the proposed structure by chemical means.

The pentacyclic intermediate (V) underwent a new type of Michael cyclization on the vinylogous amide system with acrylonitrile and methyl vinyl sulphone to give regio- and stereo-specific bridge formation producing the hexacyclic compounds which constitute the aspidofractinine (I) skeleton.