No abstract

Sztmmary Proton magnetic resonance provides direct evidence for the inclusion nature of cycloheph-amylose complex formation with aromatic substrates.CYCLOAMYLOSBS (cyclodextrins) have been used as models for enzymes1P2 and proteins,3p4 because their structures are well defined3 s5 p6 and because they interact with many substrates in a manner similar to that of enzymes and proteins. It has been ~uggestedl-~ p7 y 8 that cycloamyloses form inclusion complexes with organic substrates in aqueous solution. Little direct evidence has yet been presented (except from X-ray investigation of several crystalline complexes9 ,lo) verifying inclusion of a molecular substrate within the cavity of cycloamylose.We present the first such evidence from proton magnetic resonance (1H n.m.r.) studies of the interaction of cyclohepta-amylose (C7A) (Figure la) with a variety of aromatic substrates in aqueous solution. Previous n.m.r.'j and X-ray5 studies have unequivocally established the C-1 chair conformation for the constituent glucose units in cycloarnyloses. Cyclohepta-amylose thus has primary and secondary hydroxy-groups crowning opposite ends of its torus, H-3 a n d H-6 directed toward its interior and H-1, H-2, and H-4 located on its exterior. It was expected? a priori, in light of the screening environment associated with aromatic rnoieties,ll that if inclusion does indeed occur, protons located within or near the cavity (e.g. H-3, H-5, or H-6) should be strongly shielded.:: Alternatively, if association takes place a t the exterior of the torus, H-1, H-2, and H-4 shoulcl be the more strongly affected.The effect on the high resolution lH n.m.r. spectrum of

RSCHs + CHgSCl -> RSSCHs + Ch CH3 I (±)-RCl + CH3SSCH3 (4) this reaction using (-)-IIb and find it to be very rapid at room temperature-giving racemic 1-phenylethyl chloride and methyl disulfide consistent with rapid formation and racemization of IV as the reactive intermediate.14Reactions of I with other nucleophiles of the type RX where R is 1-phenylethyl and X is SH, SR, SSCH3, OH, and OCH3 were studied with very similar results. The products are listed in Table I and, while they may appear more complex than for lib X = SCH3, they can be rationalized by formation of alkylthio-and dialkylthiosulfonium salts related to IV that suffer migration of the 1-phenylethyl group along the sulfur chain prior to capture of this group by dialkyl sulfides.These results signify that a polysulfide is an exceptionally labile leaving group in Sn reactions and that sulfides can behave as alkylating agents when the sulfur is methylthiolated. It is also possible that the rearrangement reported here is related to the allylic rearrangement described recently in the reaction of allylic thioethers with elemental sulfur16 in which case it seems unlikely that a free carbonium ion is involved. ( 14) Related reactions of methanesulfenyl chloride with optically active alcohols are reported to result in alkyl chlorides with a high degree of inversion: I, B.

A conformational analysis of the major active constituent of marijuana and its analogs is described. From Westheimer and extended Hiickel molecular orbital calculations, structures and energies are obtained for /-A9-tetrahydrocannabinol (THC) (1), A6a(10a>-THC (2), hexahydrocannabinol (HHC) (3), and cannabinol (4). Conclusions reached on the basis of these studies, concerning the conformation of the pyran ring, the preferred orientation of the phenolic O-H bond, and ring C conformational preferences in 1, 2, 3, and A8-THC (5), are in substantial agreement with pmr observations resulting from nuclear Overhauser effect and solvent effect studies.

The initial discovery by Hinckley1 of the effectiveness of the dipyridine adduct of the rare earth complex tris(dipivalomethanato)europium(III) [Eu(DPM)3 • 2py]