The synthesis of all the possible isomers of the eburnameninevincamine type alkaloids l b , 2a*, 3a and derivatives 4, 8, 9, 10 is described. Structures were determined by 'H-and 13C-NMR spectroscopy including special techniques such as DR, DEPT, DNOE, and 2D-HSC. In contrast to the known cerebrovascular effects of cis-(3S,lGS) compounds, trans-(3S,lGR) derivatives show a significant peripheral vasodilator effect.

2-Methy lamín o-1-cyclopen tene-1-dithiocarboxy lie acid (II) can be obtained in low yield from cyclopentanone with, carbon disulfide and methylamine; no other 2-alkylamino analogs can be synthesized. The amino group of 2-amino-1-cyclopen tene-1-d.ithiocarboxylic acid (I) and that of its methyl ester (VII) can be substituted by the alkylamino group by an amine exchange reaction, yielding the corresponding 2-alkylamino-1-cyclopen tene-1dithiocarboxylic acid (II) or its methyl ester (III-V, VIII-XII), respectively. The structures, including tautomeric forms of the synthesized compounds, were proved by ir and nmr spectroscopy.In previous research it was found that 2-amino-lcyclopentene-l-dithiocarboxylic acid (I) synthesized by Takeshima and coworkers8 exerts a marked antifungal action against various fungi.4 The steric arrangement of the functional groups in this compound permits the formation of six-membered chelates with metals, which fact may be responsible for the biological activity, too. Chelation plays an important role in the

and PAL SOHAR. Can. J. Chem. 67, 1392Chem. 67, (1989.2-Flurophenyl-and 2,5-bis(fluoropheny1)pyrrolidin-1-oxyls (2 and 6) were synthesized from the corresponding nitrones 1,4, and 5 with the Grignard reagent prepared from 1-bromo-4-fluorobenzene. The reaction of 2,2,5,5-tetramethyl-3-fomyl-3-pyrrolin-1-oxyl (8) with (4-FC,&14)2Cd gave 2,2,5,5-tetramethyl-3-(a-hydroxy-4-fluorobenzy1)-3-pyrrolin-l-oxyl (9), which was oxidized with Mn02 to 2,2,5,5-tetramethyl-3-(4-fluorobenzoyl)-3-pymlin-l-oxyl(10). The aryl nitroxides 2, 6, and 10 were nitrated with concentrated H2S04/HN03 to ortho-fluoronitrophenyl compounds 3,7, and 11. The fluoro nitro derivatives served as versatile synthons in the nucleophilic replacement of fluorine with OH, NH2, a-amino acid ester, or thiol. The hydroxy nitroaryl compounds 16, 26, and 30 were nitrated further to give dinitrophenol derivatives 17, 27, and 31.

The four possible isomers of 16‐hydroxymethyl‐3‐methoxyestra‐1,3,5(10)‐trien‐17‐ol were converted into the 16‐tolylsulfonyloxymethyl‐17‐acetoxy esters 1b, 3b, 4b, 7b and into the 16‐tolylsulfonyloxymethyl‐17‐tetrahydropyranyl acetals 1c, 3c, 4c, 7c. On alkaline methanolysis of 1b and 7b, the α and β oxetanes 2 and 8 condensed to the D ring in the sterane skeleton were formed, while 3b and 4b yielded the fragmented product 5. Under similar experimental conditions, the acetals 1c, 3c, 4c, 7c were transformed into the 16‐methoxymethyl derivatives 1d, 3d, 4d, 7d.

Reactivity of 3-(1-acylhydrazonoethyl)-2H-pyran-2-ones treatment of acetylhydrazone 4a with AcC1/PhNMe2. With la-k and 4a-d towards various acetylating agents and ni-concomitant N-N bond cleavage acylhydrazones lc-f were trous acid, respectively, is studied. Treatment of dehydroa-converted to the pyrano-isoxazole 6 by treatment with cetic acid (DHA) (thi0)acylhydrazones la, c, f with Ac20/ NaN02/AcOH whereas coumarin derivative 4d was conEt3N afforded the 3-( I-triacetylhydrazinoethenyl) derivative verted to the imine 4e. 3a. The analogous coumarin derivative 5 was obtained by As a continuation of our studies of the synthesis of 3-acyl-1,3,4-thiadiazolines involving dehydrocyclization of aldehyde or ketone thiosemicarbazones under acylating conditions, recently we observed[ll an unexpected reaction of tricarbonylmethane derivatives [3-( 1 -thiosemicarbazonoethyl)triacetic acid lactone (la) and -4-hydroxycoumarin (4c)l accompanied by C,,,-C bond cleavage to give 2-acylamino-5-methyl-1,3,4-thiadiazoles along with triacetic acid lactone (ta) and 4-acetoxycoumarin.The present work is a comparative study of some analogous acylhydrazones with the less nucleophilic carbonyl group in relation to the thiocarbonyl group of thiosemicarbazones. Although under acylating conditions degradation of semicarbazones with simultaneous formation of diacylhydrazones or 5-substituted 3-acyl-1,3,4-0xadiazolines may treatment of dehydroacetic acid (DHA) semicarbazone (lc) with Ac20/ZnC12 at room temp. for 24-40 h afforded only the starting material (lc), DHA (2b), and an unidentified yellow byproduct (m.p. 233 "C, from DMSO with addition of water). With hot Ac20, however, degradation to DHA (2b) occurred. Treatment of benzoylhydrazone l h with Ac~O/pyridine at room temp. for 2.5 days did not give any well definable products, and from the reaction mixture only unchanged l h could be isolated in ca. 19% yield. In hot Ac20 l h underwent an intense decomposition. Treatment of isonicotinoylhydrazone l i with Ac20/ ZnClz for 3 days at room temp. afforded DHA in ca. 80% yield.Thus, presumably due to an equilibrium 1A + lB, the above acetylating agents are not suitable for the preparation of the corresponding diacylhydrazones or the isomeric 1,3,4-oxadiazoline derivatives.Upon treatment with Ac20 and a large excess of Et3N at room temp. DHA phenylthiosemicarbazone (lb) could be transformed [l] into the 1,3,4-thiadiazoline derivative. A similar treatment of DHA thiosemicarbazone l a resulted, however, in the formation of a sulfur-free substance. This compound was obtained by treating DHA semicarbazone l c or acetylhydrazone 1 f under the same conditions [*I Present address: Egyetem sugarut 36, H-4027 Debrecen, Hungary.(see Table 1 and Experimental). The 4-acetoxy-3-( 1 -triacetylhydrazinoethenyl)-6-methyI-2H-pyran-2-one (3a) structure of this product was proven on the basis of its IR-and NMR spectral data (see Experimental). The presence of an ethenyl moiety in 3a was confirmed by the chemical shift of the methylene carbon atom assigned by DEPT...