J. Cymerman Craig

Optical rotatory dispersion and absolute configuration—III : Pyrrolidine, piperidine and tetrahydroisoquinoline alkaloids

Abstract Optical rotatory dispersion measurements on pyrrolidine, piperidine, and tetrahydro-isoquinoline alkaloids indicate that the absolute configuration of the α-asymmetric center may be assigned directly from the dispersion curve, provided either that the nitrogen atom is not protonated, or that the compound contains a chromophore absorbing above 200 mμ.

Dual carbon-labeled isotope experiments using D-[6-14C] glucose and L-[1,2,3-13C3] lactate: A new approach for investigating human myocardial metabolism during ischemia

Simultaneous lactate production and extraction have been previously demonstrated in the myocardium in patients with coronary artery disease. To quantitate this lactate production and determine its source, dual carbon-labeled isotope experiments were performed. L-[1,2,3-13C3] lactate and D-[6-14C] glucose were infused in 10 patients with significant coronary artery disease. Metabolic samples were obtained at rest and during atrial pacing. Despite net chemical myocardial lactate extraction in the 10 patients at rest and no evidence of clinical ischemia, the L-[1,2,3-13C3] lactate analysis demonstrated that lactate was being released by the myocardium. During atrial pacing, seven patients did not develop clinical symptoms of ischemia, and the chemical lactate analysis showed net lactate extraction. However, tracer analysis demonstrated that there was a significant increase in the lactate released during atrial pacing (from 6.9 +/- 2.3 to 16.2 +/- 10.1 mumol/min) (p less than 0.05). In these seven patients, circulating glucose was the source of 23 +/- 15% of the lactate released at rest, and there was no significant change during pacing. The remaining three patients had mild chest pain and net chemical lactate production during pacing. Lactate release detected by the tracer increased from 5.7 +/- 3.0 mumol/min at rest to 50.9 +/- 16.8 mumol/min during pacing (p less than 0.01). In these patients, the contribution of glucose to lactate production increased significantly during pacing-induced clinical ischemia from 25 +/- 22 to 67 +/- 14% (p less than 0.005). Thus, dual carbon-labeled isotopic experiments are powerful tools for investigating myocardial metabolic pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

Optical rotatory dispersion and absolute configuration—I : α-Amino acids☆

Abstract Optical rotatory dispersion measurements of six enantiomeric pairs of α-amino acids, both in neutral and in acidic solution, have shown that the direction and slope of the ORD curve between 200 and 225 mμ will indicate the absolute configuration of the α-asymmetric center.

Optical rotatory dispersion and absolute configuration—IV: α-Substituted alcohols and their derivatives

Abstract Optical rotatory dispersion measurements on α-hydroxy acids, α-substituted alcohols, and their derivatives indicate that a knowledge of the dispersion curve between 200 and 225 mμ permits the direct assignment of the absolute configuration of these compounds. In this way the configurational identity of d -glyceric acid, d -serine, d -lactic acid and d -alanine with d -glyceraldehyde has been confirmed, and compounds derived from, or related, to, α-substituted alcohols may thus be correlated with d -glyceraldehyde.

The optical rotary dispersion and circular dichroism of α-amino and α-hydroxy acids

Abstract The weak negative long-wavelength (230–245 nm) CD maxima in α-amino- and α-hydroxy acids of the S-configuration (in addition to the known strong positive CD maximum in the 210–215 nm region) is shown not to be caused by hydrogen bonding effects. It is related to the nucleophilic character of the heteroatom attached to the asymmetric center, and is suggested to be due to the existence of two conformers, in one of which coupling of the non-bonding orbital of the heteroatom with the chromophoric transition of the carbonyl may occur.

Optical rotatory dispersion and absolute configuration—II : Aporphine alkaloids

Abstract The absolute configuration of aporphine alkaloids may be simply determined from the sign of their high-amplitude Cotton effect centered at 235−245 mμ.

Electron impact promoted fragmentation of some phenothiazine derivatives

Abstract The mass spectra of phenothiazines variously substituted with chloro, hydroxy, methoxy and acetoxy functions have been measured. Mass spectrometry is able to differentiate readily between oxygenation at C-3 versus C-6, C-7 and C-8 in 2-chloro-10-(3′-dimethylaminopropyl)phenothiazine (chlorpromazine) and 2-chlorophenothiazine, although (with the exception of OMe substitution in the latter series) it will not unambiguously distinguish between isomers oxygenated at C-6, C-7 or C-8. Possible mechanistic rationalizations are presented for the origin of the principal ions in the mass spectra of the compounds investigated.

Optical rotatory dispersion and absolute configuration—X α- and β-phenylethylamine S

Abstract ORD and CD measurements on α- and β-phenylethylamines and a cyclic analogue possessing the benzoquinolizidine structure indicate that the absolute configuration of the asymmetric center may be assigned from the ORD curve. Compounds of S-configuration exhibit a positive multiple Cotton effect between 270 and 250 mμ.

Amine-N-oxide rearrangements : Mechanism and products of thermolysis☆

Abstract The thermolysis of a series of structurally similar amine-N-oxides has been examined individually and as mixtures. Product analysis shows that in addition to the expected N-alkoxylamines, smaller amounts of t-amines, aldehydes, and bibenzyls are formed. Thermolysis of mixtures produces intermolecular rearrangement products thus challenging the previously favored intramolecular mechanism as the exclusive process for the Meisenheimer rearrangement. The data are consistent with a mechanism involving homolytic fission to intermediates which recombine to produce the N-alkoxylamines.

The configuration and conformation of cularine

Abstract The absolute configuration of cularine has been shown to be d (= R) from the ORD of its hydrogenolysis product (VIII). The hydrochloride, methiodide and O-acetate of VIII showed a complete reversal of the long-wavelength Cotton effect and CD maximum at 290 mμ, while the short-wavelength Cotton effects at 226 and 210 mμ remained unaffected. This reversal is attributed to steric hindrance to rotation of the 2′-substituted benzyl moiety. NMR spectra at 100 mc/s permit the assignment of one of the 3 possible bent conformations to cularine.