No abstract

Nuclear Overhauser difference spectroscopy and variable temperature studies of the 9.3,19-cyclopropyl sterols 24,25-dehydropollinastanol (4,4-desmethyl-5a-cycloart-24-en-3fi-ol) and cyclolaudenol [(24S)-24-methyl-5a-cycloart-25(27)-en-3,3-ol] have shown the solution conformation ofthe B/C rings to be twist-chair/twist-boat rather than boat/ chair as suggested in the literature. This is very similar to the known crystal structure conformation of 9,3,19-cyclopropyl sterols. The effect of these conformations on the molecular shape is highly significant: the first conformation orients into a pseudoplanar or flat shape analogous to lanosterol, whereas the latter conformation exhibits a bent shape. The results are interpreted to imply that, for conformational reasons, cyclopropyl sterols can be expected to maintain the pseudoplanar shape in membrane bilayers.For reasons that are still unknown, organisms having a photosynthetic lineage cyclize squalene oxide to the 9f3,19-cyclopropyl sterol (CS) cycloartenol, while organisms having an evolutionary history that is completely nonphotosynthetic cyclize squalene oxide to the isomeric tetracycle lanosterol (1, 2). Cycloartenol has been shown to isomerize to lanosterol under acidic conditions (3) and during routine metabolism in plants (2). In lanosterol the 8,9 double bond approximates a trans structure for the B/C ring junction, maintaining a flat conformation of the molecule. However in CSs the 9,10 cyclopropyl bridgehead and the ,B oriented hydrogen at C-8 approximate a syn-cis configuration at the A/C and B/C ringjunctions. Some investigators believe (3-8) that this configurational disposition bends the plane of the molecule at the B/C ring junction through almost 90°. Dreiding models also show the molecule is no longer flat in the bent shape but neither they nor stereochemical considerations of polycyclic systems show that CSs could orient into the exaggerated "curvilinear belt" described by Bloch (4). That the configuration of the ring junctures influences the overall conformation of the molecule is known (8) in the isomeric pair of saturated sterols cholestanol and coprostanol. Here, inversion of the configuration of H-5 changes the A/B ring juncture stereochemistry from flat

Formylation of solasodine results in the formation of two different 3,N-diformylsolasodines whose isomerism is due to a difference in stereochemistry at C22 rather than restricted rotation about the C = N partial double bond of the amide or nitrogen inversion as previously proposed. Mass spectra, 'H and I3C n.m.r. spectra have shown the isomers to possess 22R,25R (major) and 22S,25R (minor) stereochemistry. The 22S,25R isomer is thermodynamically preferred at elevated temperatures while the 2212,2513 isomer is kinetically favoured upon recyclization of the ring-F opened intermediate which forms upon heating of either isomer. A non-chair ring-P conformation is proposed for each isomer on the basis of 13C and 'H n.m.r. spectra. mixture of the isomeric N-formylsolasodines. This study reports a detailed investigation of the isomeric (25R)-N-formyl-22N-spiroso1-5-en-3j3-y1 formates (3,Ndiformylsolasodines) by mass spectrometry, 13C and 'H n.m.r. spectroscopy which has led to assignment of structures (1) and (2) to these compounds. Results and DiscussionAddition of formic-acetic anhydride to a chloroform solution of solasodine yielded isomeric diformylsolasodines in a ratio of approximately 2 : 1. The major isomer (I) gave a 'H n.m.r. spectrum corresponding to that reported1 for isomer (B) while the minor isomer (2) afforded a 'H n.m.r. spectrum resembling that reported1 for isomer (A). Formylation of tomatidine under similar conditions yielded a single diformyl derivative (3). 'H and 13C N.M.R. SpectraDue to conflicting assignments reported by two groups of ~o r k e r s ' ,~ for 'H n.m.r. signals of the H21 and H27 [see structure (4) for numbering] methyl groups of (1) and (2), proton decoupling experiments were performed in order to unequivocally establish the position of the resonance for each methyl group (Table 1). Irradiation of (2), in CDCl,, at 6 2.30 (H20) collapsed only the downfield methyl doublet at 6 1.14 while irradiation at 6 1.80 (H 25) collapsed signals due to each of the H26 protons at 6 3.88 and 3.13 in addition to the upfield methyl doublet at 6 0.94. Similar results were obtained for (1) in C,D,, a solvent in which the upfield H26 resonance moved downfield relative to its position in CDCl, enabling it to be observed. These results confirm the assignments originally reported1 by Toldy and Radics and enable assignment of H 27 to the upfield methyl doublet. Furthermore, we have confirmed the report1 that the upfield H 26 has a trans (7-9 Hz) coupling to the H 25 proton in (1) and (2).

No abstract