Biosynthesis of verrucarins and roridins. 2. Incorporation of acetate in cis-transmuconic acid and of mevalonate in roridinic acid]

Incorporation experiments using sodium [1-¹⁴C]-acetate and sodium [2-¹⁴C]- and [2-¹⁴C,2-³H₂]-mevalonate and degradations of the verrucarin A ( 1 ) and roridin A ( 2 ) so produced demonstrate that cis,trans-muconic acid ( 3 ) is formed from 3 acetate units. The cis,trans-muconic acid and the C₂-side-chain structural elements of roridinic acid ( 6 ) are built up from 4 acetate units; the cis-oricntcd C(11)-carboxyl group of 6 originates from C(1) of acctic acid. The structural moiety of roridinic acid ( 6 ) corresponding to verrucarinic, acid ( 7 ) originates from mevalonate, as does 7 . A new degradation scheme was devised for roridinic acid ( 6 ); the oxime 23 of its 13 dehydro-detrahydro derivative 21 underwent cleavage with SOCl₂ and subsequent hydrolysis to yield verrucarinolactone ( 8 ), acetonitrile ( 26 ) and methyl adipaldohydate ( 27 ) by a heterolytic Beckmann fragmentation reaction.     

Biosynthesis of the verrucarins and roridins. Part 4. The mode of incorporation of (3R)-((5R)-5-3H)-mevalonate into verrucarol. Evidence for the identity of the C(11)-hydrogen atom of the trichothecane skeleton with the (5R)-hydrogen atom of (3R)-mevalonic acid.

Incorporation of (3R)-[(5R)-5-³H]-mevalonate into verrucarin followed by hydrolyses to verrucarol (2) and transformation of the latter to the spirolactol 5 and the spirolactone 6 successively, demonstrate the identity of the C(11)-hydrogen of the trichothecane skeleton with the 5-‘pro-R’ hydrogen atom of (3R)-mevalonate.     

Biosynthesis of the antibiotic verrucarin E use of [1-13C]-, [2-13C]-, [1,2-13C]- and [2-13C, 2-2H3]-acetates. Verrucarins and roridins, 37th communication [1]

The origin of the carbon skeleton of verrucarin E (1) from acetate as precursor is confirmed. Incorporation studies with [1,2-¹³C]-acetate have demonstrated that two acetoacetate units couple together as shown in pattern A (Scheme 2) and not as in B . Analysis of the deuterium distribution in both verrucarin E (1) isolated after the incorporation of [2-¹³C,2-²H₃]-acetate and in sodium acetate obtained after Kuhn-Roth oxidation of the metabolite demonstrated that C(7) is derived from the starter unit of one of the acetoacetate moieties. The deuterium exchange in verrucarin E (1) occurring during fermentation was investigated.     

2-Polyfluoroalkylchromones. 14. Synthesis of 4-chloro-3(5)-(2-hydroxyaryl)-5(3)-polyfluoroalkylpyrazoles

3-Chloro-2-polyfluoroalkyl- and 3-chloro-6-nitro-2-polyfluoroalkylchromones were synthesized. These compounds react with N₂H₄·2HCl on boiling in ethanol to form 4-chloro-3(5)-(2-hydroxyaryl)-5(3)-polyfluoroalkylpyrazoles.     

Psilocin analogs. 1. Synthesis of 3-[2-(dialkylamino)ethyl] -and 3-[2-(cycloalkylamino)ethyl] indol-4-ols

The synthesis of four dialkyl and three eyeloalkyl analogs of psilocin (4, R - CH₃), a hallucinogenic principle found in certain fungi, is described. The synthetic route involves four transformations starting with 6,7-dihydroindol-4(5H)one: (1).     

Pyridine-substituted hydroxythiophenes. V. Preparation of 5-(2-, 3-and 4-pyridyl)-2-hydroxythiophenes

5-(2-, 3- and 4-Pyridyl)-2-t-butoxythiophenes have been prepared in very good yields by Pd(0) catalyzed cross-coupling of the three isomeric bromopyridines with 5-trimethylstannyl-2-t-butoxythiophene derived from 2-bromothiophene via 2-t-butoxythiophene. Dealkylation of 5-(2-, 3- and 4-pyridyl)-2-t-but-oxythiophenes with boron trifluoride etherate in dichloromethane at room temperature led to predominant formation of rearranged products, 5-(2- and 3-pyridyl)-3-t-butyl-3-thiolene-2-ones, together with a small amount of 5-(2- and 3-pyridyl)-2-hydroxythiophenes as a mixture of two tautomeric keto forms in the case of the 2-pyridyl and the 3-pyridyl isomers, and exclusive formation of rearranged product in the case of the 4-pyridyl isomer. However, dealkylation of 2-methoxy-5-(2-, 3- and 4-pyridyl)thiophenes, prepared similarly to the 5-(2-, 3- and 4-pyridyl)-2-t-butoxythiophenes, with boron tribromide under the same reaction conditions as above resulted exclusively in the tautomeric mixture of 5-(2- and 3-pyridyl)-3-thiolene-2-ones and 5-(2- and 3-pyridyl)-4-thiolene-2-ones in the case of the 2-pyridyl and 3-pyridyl isomers. In the case of the 4-pyridyl isomer polymerization took place.     

First Enantioselective Synthesis of (2R,3R)-and(2S,3S)-2-(4-hydroxyphenyl)-3-hydroxymethyl-1,4-benzodioxan-6-carbaldehyde

Numerous lignans containing 1,4-benzodioxane nucleus represent a class of natural products with cytotoxic and hepatoprotective activities1,2. Recently we have reported the racemic total synthesis of sinaiticin, a flavonolignan of the 1,4-benzodioxane type which was isolated from sinaiticum leaves found in sinai region of Egypt, using 2-(4-hydroxyphenyl)-3-hydroxymethyl-1,4-benzodioxan-6-carbaldehyde as the key interme-diate3,4. This species exhibits significant inhibitory activity against the …     

Syntheses of (R) [4-2H2] 2-Amino-3-Butenoic Acid (Vinylglycine) and (R) [4-2H2, 5-2H3] Methionine

Treatment of (R) methionine sulfoxide with NaOD led to exchange of the C-4 methylene and C-5 methyl protons; exchange of the chiral C-2 proton did not occur. Reducation with mercaptoacetic acid gave (R)-[4-²H₂, 5-²H₃] methionine. The latter was converted into its carbobenzyloxy methyl ester sulfoxide, pyrolysis of which followed by deprotection yielded (R)-[4-²H₂] vinylglcine as the hydrochloride.     

Optically active organoaluminum based inclusion compounds. Synthesis and characterization of (S)-(−)-α-[(C6H5)CH(CH3)N(CH3)3][Al2R6I] (R=CH3, C2H5)

The optically active quaternary ammonium salt (S)-(?)-α-[(C₆H₅)CH(CH₃)N(CH₃)₃I] reacts with AlR₃ to afford optically active organoaluminum based inclusion compounds, liquid clathrates, of the formula (S)-(?)-α-[(C₆H₅)CH(CH₃)N(CH₃)₃][Al₂R₆I] (R=CH₃, C₂H₅). Specific rotation ([α] ₂₅ ^D ) for the Al(CH₃)₃ compound was determined to be ?13.19° while that for the Al(C₂H₅)₃ analog was determined to be ?14.30°. There are 13.8 toluene molecules per anionic moiety for the trimethylaluminum based liquid clathrate while there are 15.0 toluene molecules per anion for the corresponding triethylaluminum inclusion compound.