The Structure of Riddellic Acid and the Stereochemistry of Necic Acids

Abstract

1 further study of the structure of riddellic acid has led to rejection of the previously proposed formula IIIa in favor of formula IVa. The evidence for formula IYa is based on the ultraviolet and n m.r. spectra of dimethyl riddellate and the dimethyl ester of a-methylene-a'-ethylideneglutaric acid, the lead tetraacetate oxidation product of riddellic acid. Chemical confirmation for the terminal methylene group is provided by oxidation of a-methylene-a'-ethylideneglutaric acid with osmium tetroxide and sodium metaperiodate and isolation of formaldehyde as its dimedone derivative. The comparison of the n.m.r. spectra of a variety of analogous natural acids and esters with trisubstituted cr,B-olefinic acids and esters revealed that from the position of the olefinic proton peak, the cis or trans configuration of the trisubstituted olefinic acid can be estabished.The structure of riddellic acid, the alkaline hydrolysis product of the alkaloid riddelline, was the subject of a previous paper from this Laboratory.' Convincing evidence was presented for the presence of two double bonds, an a-hydroxy acid and a glycol system in riddellic acid. The close similarity of the infrared and ultraviolet spectra of riddellic acid, seneciphyllic acid and of their retronecine and dimethyl esters indicated that the double bonds in these two acids are similarly situated. The structure of seneciphyllic acid previously had been proposedl as I ; the alternate structure IT for seneciphyllic acid was considered a t that time but structure I was preferred since no formaldehyde was obtained on ozonolysis, Ruhn-Roth determination gave a value 2.2 for C-methyl groups, and the infrared spectrum failed to show the characteristic absorption for a terminal methylene group. By analogy, then, riddellic acid was represented as I11 H3C CHI H:C CHI

(+)-Trienomycins A, B, C, and F and (+)-Mycotrienins I and II: Relative and Absolute Stereochemistry

“…In conjunction with homonuclear decoupling experiments, which verified the 6.9-Hz coupling between the resonances at δ 1.75 and 6.53, these data were indicative of a 2-methyl-2-butenamide unit. Comparison of the chemical shift for the C(31) vinylic proton in (+)- 13 with the corresponding resonances for methyl tiglate ( 43a ), methyl angelate ( 44a ), and the derived N -acyl- d -alanine methyl esters 43b and 44b then established the E geometry of the C(30,31) olefin (Table ).…”

Synthesis of long chaina,B‐alkynoic anda,B‐alkynoic acids viaB‐keto esters

“…Perhaps the trans isomer olefinic proton appears at lower fields than the olefinic proton of the cis isomer because of steric inhibition of resonance caused by interactions of the cis alkyl and carboxyl groups in the latter case. Also, an insignificant shift occurs in the 3 value of the olefinic proton by changing the substituent from methyl to ethyl (16).…”

“…Average percentages obtained and determined by GLC and proton magnetic resonance (PMR) (16) follows: (a) 53.6% angelic acid and 46.4% tiglic acid; and (b) 62.2% 2-ethylisocrotonic acid and 37.8% ethylcrotonic acid.…”

Bromomalonates as synthetic reagents. Transfer alkylations

“…Methyl 3-Carbomethoxy-9,9-dicarbo-cyclic-isopropoxy-8methyl-2,4,6-decatrienoate (29). In a similar manner, the enolate from 224 mg (1.00 mmol) of methyl 3-carbomethoxy-3,5,7-nonatrienoate (11), generated utilizing 1.1 mmol of lithium diisopropylamide in 5 ml of dry THF, was reacted with 237 mg (1.00 mmol) of cyclic isopropylidene 2-bromo-2-methylmalonate in 5 ml of dry tetrahydrofuran.…”